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Erschienen in: Reviews in Endocrine and Metabolic Disorders 4/2013

01.12.2013

Brain regulation of energy balance and body weight

verfasst von: Liangyou Rui

Erschienen in: Reviews in Endocrine and Metabolic Disorders | Ausgabe 4/2013

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Abstract

Body weight is determined by a balance between food intake and energy expenditure. Multiple neural circuits in the brain have evolved to process information about food, food-related cues and food consumption to control feeding behavior. Numerous gastrointestinal endocrine cells produce and secrete satiety hormones in response to food consumption and digestion. These hormones suppress hunger and promote satiation and satiety mainly through hindbrain circuits, thus governing meal-by-meal eating behavior. In contrast, the hypothalamus integrates adiposity signals to regulate long-term energy balance and body weight. Distinct hypothalamic areas and various orexigenic and anorexigenic neurons have been identified to homeostatically regulate food intake. The hypothalamic circuits regulate food intake in part by modulating the sensitivity of the hindbrain to short-term satiety hormones. The hedonic and incentive properties of foods and food-related cues are processed by the corticolimbic reward circuits. The mesolimbic dopamine system encodes subjective “liking” and “wanting” of palatable foods, which is subjected to modulation by the hindbrain and the hypothalamic homeostatic circuits and by satiety and adiposity hormones. Satiety and adiposity hormones also promote energy expenditure by stimulating brown adipose tissue (BAT) activity. They stimulate BAT thermogenesis mainly by increasing the sympathetic outflow to BAT. Many defects in satiety and/or adiposity hormone signaling and in the hindbrain and the hypothalamic circuits have been described and are believed to contribute to the pathogenesis of energy imbalance and obesity.
Literatur
1.
Zurück zum Zitat Berthoud HR. Metabolic and hedonic drives in the neural control of appetite: who is the boss? Curr Opin Neurobiol. 2011;21(6):888–96. Berthoud HR. Metabolic and hedonic drives in the neural control of appetite: who is the boss? Curr Opin Neurobiol. 2011;21(6):888–96.
2.
Zurück zum Zitat Berthoud HR. The neurobiology of food intake in an obesogenic environment. Proc Nutr Soc. 2012;71(4):478–87. Berthoud HR. The neurobiology of food intake in an obesogenic environment. Proc Nutr Soc. 2012;71(4):478–87.
3.
Zurück zum Zitat Sam AH, Troke RC, Tan TM, Bewick GA. The role of the gut/brain axis in modulating food intake. Neuropharmacology. 2012;63(1):46–56. Sam AH, Troke RC, Tan TM, Bewick GA. The role of the gut/brain axis in modulating food intake. Neuropharmacology. 2012;63(1):46–56.
4.
Zurück zum Zitat Ryan KK, Kohli R, Gutierrez-Aguilar R, Gaitonde SG, Woods SC, Seeley RJ. Fibroblast growth factor-19 action in the brain reduces food intake and body weight and improves glucose tolerance in male rats. Endocrinology. 2013;154(1):9–15.PubMed Ryan KK, Kohli R, Gutierrez-Aguilar R, Gaitonde SG, Woods SC, Seeley RJ. Fibroblast growth factor-19 action in the brain reduces food intake and body weight and improves glucose tolerance in male rats. Endocrinology. 2013;154(1):9–15.PubMed
5.
Zurück zum Zitat Moran TH, Baldessarini AR, Salorio CF, Lowery T, Schwartz GJ. Vagal afferent and efferent contributions to the inhibition of food intake by cholecystokinin. Am J Physiol. 1997;272(4 Pt 2):R1245–51.PubMed Moran TH, Baldessarini AR, Salorio CF, Lowery T, Schwartz GJ. Vagal afferent and efferent contributions to the inhibition of food intake by cholecystokinin. Am J Physiol. 1997;272(4 Pt 2):R1245–51.PubMed
6.
Zurück zum Zitat Moran TH, Katz LF, Plata-Salaman CR, Schwartz GJ. Disordered food intake and obesity in rats lacking cholecystokinin A receptors. Am J Physiol. 1998;274(3 Pt 2):R618–25.PubMed Moran TH, Katz LF, Plata-Salaman CR, Schwartz GJ. Disordered food intake and obesity in rats lacking cholecystokinin A receptors. Am J Physiol. 1998;274(3 Pt 2):R618–25.PubMed
7.
Zurück zum Zitat Suzuki K, Jayasena CN, Bloom SR. Obesity and appetite control. Exp Diabetes Res. 2012;2012:824305.PubMed Suzuki K, Jayasena CN, Bloom SR. Obesity and appetite control. Exp Diabetes Res. 2012;2012:824305.PubMed
8.
Zurück zum Zitat Lo CC, Langhans W, Georgievsky M, Arnold M, Caldwell JL, Cheng S, et al. Apolipoprotein AIV requires cholecystokinin and vagal nerves to suppress food intake. Endocrinology. 2012;153(12):5857–65.PubMed Lo CC, Langhans W, Georgievsky M, Arnold M, Caldwell JL, Cheng S, et al. Apolipoprotein AIV requires cholecystokinin and vagal nerves to suppress food intake. Endocrinology. 2012;153(12):5857–65.PubMed
9.
Zurück zum Zitat Delaere F, Magnan C, Mithieux G. Hypothalamic integration of portal glucose signals and control of food intake and insulin sensitivity. Diabetes & metabolism. 2010;36(4):257–62. Delaere F, Magnan C, Mithieux G. Hypothalamic integration of portal glucose signals and control of food intake and insulin sensitivity. Diabetes & metabolism. 2010;36(4):257–62.
10.
Zurück zum Zitat Kohan AB, Wang F, Li X, Bradshaw S, Yang Q, Caldwell JL, et al. Apolipoprotein A-IV regulates chylomicron metabolism-mechanism and function. Am J Physiol Gastrointest Liver Physiol. 2012;302(6):G628–36.PubMed Kohan AB, Wang F, Li X, Bradshaw S, Yang Q, Caldwell JL, et al. Apolipoprotein A-IV regulates chylomicron metabolism-mechanism and function. Am J Physiol Gastrointest Liver Physiol. 2012;302(6):G628–36.PubMed
11.
Zurück zum Zitat Weinstock PH, Bisgaier CL, Hayek T, Aalto-Setala K, Sehayek E, Wu L, et al. Decreased HDL cholesterol levels but normal lipid absorption, growth, and feeding behavior in apolipoprotein A-IV knockout mice. J Lipid Res. 1997;38(9):1782–94.PubMed Weinstock PH, Bisgaier CL, Hayek T, Aalto-Setala K, Sehayek E, Wu L, et al. Decreased HDL cholesterol levels but normal lipid absorption, growth, and feeding behavior in apolipoprotein A-IV knockout mice. J Lipid Res. 1997;38(9):1782–94.PubMed
12.
Zurück zum Zitat Shen L, Pearson KJ, Xiong Y, Lo CM, Tso P, Woods SC, et al. Characterization of apolipoprotein A-IV in brain areas involved in energy homeostasis. Physiol Behav. 2008;95(1–2):161–7.PubMed Shen L, Pearson KJ, Xiong Y, Lo CM, Tso P, Woods SC, et al. Characterization of apolipoprotein A-IV in brain areas involved in energy homeostasis. Physiol Behav. 2008;95(1–2):161–7.PubMed
13.
Zurück zum Zitat Gotoh K, Liu M, Benoit SC, Clegg DJ, Davidson WS, D’Alessio D, et al. Apolipoprotein A-IV interacts synergistically with melanocortins to reduce food intake. Am J Physiol Regul Integr Comp Physiol. 2006;290(1):R202–7.PubMed Gotoh K, Liu M, Benoit SC, Clegg DJ, Davidson WS, D’Alessio D, et al. Apolipoprotein A-IV interacts synergistically with melanocortins to reduce food intake. Am J Physiol Regul Integr Comp Physiol. 2006;290(1):R202–7.PubMed
14.
Zurück zum Zitat Morris DL, Rui L. Recent advances in understanding leptin signaling and leptin resistance. Am J Physiol Endocrinol Metab. 2009;297(6):E1247–59.PubMed Morris DL, Rui L. Recent advances in understanding leptin signaling and leptin resistance. Am J Physiol Endocrinol Metab. 2009;297(6):E1247–59.PubMed
15.
Zurück zum Zitat Schwartz MW, Porte Jr D. Diabetes, obesity, and the brain. Science. 2005;307(5708):375–9.PubMed Schwartz MW, Porte Jr D. Diabetes, obesity, and the brain. Science. 2005;307(5708):375–9.PubMed
17.
Zurück zum Zitat Travagli RA, Hermann GE, Browning KN, Rogers RC. Brainstem circuits regulating gastric function. Annu Rev Physiol. 2006;68:279–305.PubMed Travagli RA, Hermann GE, Browning KN, Rogers RC. Brainstem circuits regulating gastric function. Annu Rev Physiol. 2006;68:279–305.PubMed
18.
Zurück zum Zitat Hisadome K, Reimann F, Gribble FM, Trapp S. Leptin directly depolarizes preproglucagon neurons in the nucleus tractus solitarius: electrical properties of glucagon-like peptide 1 neurons. Diabetes. 2010;59(8):1890–8.PubMed Hisadome K, Reimann F, Gribble FM, Trapp S. Leptin directly depolarizes preproglucagon neurons in the nucleus tractus solitarius: electrical properties of glucagon-like peptide 1 neurons. Diabetes. 2010;59(8):1890–8.PubMed
19.
Zurück zum Zitat Zheng H, Patterson LM, Phifer CB, Berthoud HR. Brain stem melanocortinergic modulation of meal size and identification of hypothalamic POMC projections. Am J Physiol Regul Integr Comp Physiol. 2005;289(1):R247–58.PubMed Zheng H, Patterson LM, Phifer CB, Berthoud HR. Brain stem melanocortinergic modulation of meal size and identification of hypothalamic POMC projections. Am J Physiol Regul Integr Comp Physiol. 2005;289(1):R247–58.PubMed
20.
Zurück zum Zitat Geerling JC, Shin JW, Chimenti PC, Loewy AD. Paraventricular hypothalamic nucleus: axonal projections to the brainstem. J Comp Neurol. 2010;518(9):1460–99.PubMed Geerling JC, Shin JW, Chimenti PC, Loewy AD. Paraventricular hypothalamic nucleus: axonal projections to the brainstem. J Comp Neurol. 2010;518(9):1460–99.PubMed
21.
Zurück zum Zitat Appleyard SM, Marks D, Kobayashi K, Okano H, Low MJ, Andresen MC. Visceral afferents directly activate catecholamine neurons in the solitary tract nucleus. J Neurosci. 2007;27(48):13292–302.PubMed Appleyard SM, Marks D, Kobayashi K, Okano H, Low MJ, Andresen MC. Visceral afferents directly activate catecholamine neurons in the solitary tract nucleus. J Neurosci. 2007;27(48):13292–302.PubMed
22.
Zurück zum Zitat Cui RJ, Roberts BL, Zhao H, Zhu M, Appleyard SM. Serotonin activates catecholamine neurons in the solitary tract nucleus by increasing spontaneous glutamate inputs. J Neurosci. 2012;32(46):16530–8.PubMed Cui RJ, Roberts BL, Zhao H, Zhu M, Appleyard SM. Serotonin activates catecholamine neurons in the solitary tract nucleus by increasing spontaneous glutamate inputs. J Neurosci. 2012;32(46):16530–8.PubMed
23.
Zurück zum Zitat Wu Q, Clark MS, Palmiter RD. Deciphering a neuronal circuit that mediates appetite. Nature. 2012;483(7391):594–7.PubMed Wu Q, Clark MS, Palmiter RD. Deciphering a neuronal circuit that mediates appetite. Nature. 2012;483(7391):594–7.PubMed
24.
Zurück zum Zitat Cui RJ, Li X, Appleyard SM. Ghrelin inhibits visceral afferent activation of catecholamine neurons in the solitary tract nucleus. J Neurosci. 2011;31(9):3484–92.PubMed Cui RJ, Li X, Appleyard SM. Ghrelin inhibits visceral afferent activation of catecholamine neurons in the solitary tract nucleus. J Neurosci. 2011;31(9):3484–92.PubMed
25.
Zurück zum Zitat Takayanagi Y, Matsumoto H, Nakata M, Mera T, Fukusumi S, Hinuma S, et al. Endogenous prolactin-releasing peptide regulates food intake in rodents. J Clin Invest. 2008;118(12):4014–24.PubMed Takayanagi Y, Matsumoto H, Nakata M, Mera T, Fukusumi S, Hinuma S, et al. Endogenous prolactin-releasing peptide regulates food intake in rodents. J Clin Invest. 2008;118(12):4014–24.PubMed
26.
Zurück zum Zitat Hisadome K, Reimann F, Gribble FM, Trapp S. CCK stimulation of GLP-1 neurons involves alpha1-adrenoceptor-mediated increase in glutamatergic synaptic inputs. Diabetes. 2011;60(11):2701–9.PubMed Hisadome K, Reimann F, Gribble FM, Trapp S. CCK stimulation of GLP-1 neurons involves alpha1-adrenoceptor-mediated increase in glutamatergic synaptic inputs. Diabetes. 2011;60(11):2701–9.PubMed
27.
Zurück zum Zitat Barrera JG, Jones KR, Herman JP, D’Alessio DA, Woods SC, Seeley RJ. Hyperphagia and increased fat accumulation in two models of chronic CNS glucagon-like peptide-1 loss of function. J Neurosci. 2011;31(10):3904–13.PubMed Barrera JG, Jones KR, Herman JP, D’Alessio DA, Woods SC, Seeley RJ. Hyperphagia and increased fat accumulation in two models of chronic CNS glucagon-like peptide-1 loss of function. J Neurosci. 2011;31(10):3904–13.PubMed
28.
Zurück zum Zitat Hayes MR, Leichner TM, Zhao S, Lee GS, Chowansky A, Zimmer D, et al. Intracellular signals mediating the food intake-suppressive effects of hindbrain glucagon-like peptide-1 receptor activation. Cell Metab. 2011;13(3):320–30.PubMed Hayes MR, Leichner TM, Zhao S, Lee GS, Chowansky A, Zimmer D, et al. Intracellular signals mediating the food intake-suppressive effects of hindbrain glucagon-like peptide-1 receptor activation. Cell Metab. 2011;13(3):320–30.PubMed
29.
Zurück zum Zitat Scott MM, Williams KW, Rossi J, Lee CE, Elmquist JK. Leptin receptor expression in hindbrain Glp-1 neurons regulates food intake and energy balance in mice. J Clin Invest. 2011;121(6):2413–21.PubMed Scott MM, Williams KW, Rossi J, Lee CE, Elmquist JK. Leptin receptor expression in hindbrain Glp-1 neurons regulates food intake and energy balance in mice. J Clin Invest. 2011;121(6):2413–21.PubMed
30.
Zurück zum Zitat Fan W, Ellacott KL, Halatchev IG, Takahashi K, Yu P, Cone RD. Cholecystokinin-mediated suppression of feeding involves the brainstem melanocortin system. Nat Neurosci. 2004;7(4):335–6.PubMed Fan W, Ellacott KL, Halatchev IG, Takahashi K, Yu P, Cone RD. Cholecystokinin-mediated suppression of feeding involves the brainstem melanocortin system. Nat Neurosci. 2004;7(4):335–6.PubMed
31.
Zurück zum Zitat Appleyard SM, Bailey TW, Doyle MW, Jin YH, Smart JL, Low MJ, et al. Proopiomelanocortin neurons in nucleus tractus solitarius are activated by visceral afferents: regulation by cholecystokinin and opioids. J Neurosci. 2005;25(14):3578–85.PubMed Appleyard SM, Bailey TW, Doyle MW, Jin YH, Smart JL, Low MJ, et al. Proopiomelanocortin neurons in nucleus tractus solitarius are activated by visceral afferents: regulation by cholecystokinin and opioids. J Neurosci. 2005;25(14):3578–85.PubMed
32.
Zurück zum Zitat Maejima Y, Sedbazar U, Suyama S, Kohno D, Onaka T, Takano E, et al. Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes anorexia through a leptin-independent melanocortin pathway. Cell Metab. 2009;10(5):355–65.PubMed Maejima Y, Sedbazar U, Suyama S, Kohno D, Onaka T, Takano E, et al. Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes anorexia through a leptin-independent melanocortin pathway. Cell Metab. 2009;10(5):355–65.PubMed
33.
Zurück zum Zitat Li G, Zhang Y, Rodrigues E, Zheng D, Matheny M, Cheng KY, et al. Melanocortin activation of nucleus of the solitary tract avoids anorectic tachyphylaxis and induces prolonged weight loss. Am J Physiol Endocrinol Metab. 2007;293(1):E252–8.PubMed Li G, Zhang Y, Rodrigues E, Zheng D, Matheny M, Cheng KY, et al. Melanocortin activation of nucleus of the solitary tract avoids anorectic tachyphylaxis and induces prolonged weight loss. Am J Physiol Endocrinol Metab. 2007;293(1):E252–8.PubMed
34.
Zurück zum Zitat Wan S, Browning KN, Coleman FH, Sutton G, Zheng H, Butler A, et al. Presynaptic melanocortin-4 receptors on vagal afferent fibers modulate the excitability of rat nucleus tractus solitarius neurons. J Neurosci. 2008;28(19):4957–66.PubMed Wan S, Browning KN, Coleman FH, Sutton G, Zheng H, Butler A, et al. Presynaptic melanocortin-4 receptors on vagal afferent fibers modulate the excitability of rat nucleus tractus solitarius neurons. J Neurosci. 2008;28(19):4957–66.PubMed
35.
Zurück zum Zitat Huo L, Grill HJ, Bjorbaek C. Divergent regulation of proopiomelanocortin neurons by leptin in the nucleus of the solitary tract and in the arcuate hypothalamic nucleus. Diabetes. 2006;55(3):567–73.PubMed Huo L, Grill HJ, Bjorbaek C. Divergent regulation of proopiomelanocortin neurons by leptin in the nucleus of the solitary tract and in the arcuate hypothalamic nucleus. Diabetes. 2006;55(3):567–73.PubMed
36.
Zurück zum Zitat Sohn JW, Harris LE, Berglund ED, Liu T, Vong L, Lowell BB, et al. Melanocortin 4 receptors reciprocally regulate sympathetic and parasympathetic preganglionic neurons. Cell. 2013;152(3):612–9.PubMed Sohn JW, Harris LE, Berglund ED, Liu T, Vong L, Lowell BB, et al. Melanocortin 4 receptors reciprocally regulate sympathetic and parasympathetic preganglionic neurons. Cell. 2013;152(3):612–9.PubMed
37.
Zurück zum Zitat Herbert H, Moga MM, Saper CB. Connections of the parabrachial nucleus with the nucleus of the solitary tract and the medullary reticular formation in the rat. J Comp Neurol. 1990;293(4):540–80.PubMed Herbert H, Moga MM, Saper CB. Connections of the parabrachial nucleus with the nucleus of the solitary tract and the medullary reticular formation in the rat. J Comp Neurol. 1990;293(4):540–80.PubMed
38.
Zurück zum Zitat Jhamandas JH, Harris KH. Excitatory amino acids may mediate nucleus tractus solitarius input to rat parabrachial neurons. Am J Physiol. 1992;263(2 Pt 2):R324–30.PubMed Jhamandas JH, Harris KH. Excitatory amino acids may mediate nucleus tractus solitarius input to rat parabrachial neurons. Am J Physiol. 1992;263(2 Pt 2):R324–30.PubMed
39.
Zurück zum Zitat Rinaman L. Ascending projections from the caudal visceral nucleus of the solitary tract to brain regions involved in food intake and energy expenditure. Brain Res. 2010;1350:18–34.PubMed Rinaman L. Ascending projections from the caudal visceral nucleus of the solitary tract to brain regions involved in food intake and energy expenditure. Brain Res. 2010;1350:18–34.PubMed
40.
Zurück zum Zitat Alhadeff AL, Rupprecht LE, Hayes MR. GLP-1 neurons in the nucleus of the solitary tract project directly to the ventral tegmental area and nucleus accumbens to control for food intake. Endocrinology. 2012;153(2):647–58.PubMed Alhadeff AL, Rupprecht LE, Hayes MR. GLP-1 neurons in the nucleus of the solitary tract project directly to the ventral tegmental area and nucleus accumbens to control for food intake. Endocrinology. 2012;153(2):647–58.PubMed
41.
Zurück zum Zitat Dossat AM, Lilly N, Kay K, Williams DL. Glucagon-like peptide 1 receptors in nucleus accumbens affect food intake. J Neurosci. 2011;31(41):14453–7.PubMed Dossat AM, Lilly N, Kay K, Williams DL. Glucagon-like peptide 1 receptors in nucleus accumbens affect food intake. J Neurosci. 2011;31(41):14453–7.PubMed
42.
Zurück zum Zitat Elias CF, Lee C, Kelly J, Aschkenasi C, Ahima RS, Couceyro PR, et al. Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron. 1998;21(6):1375–85.PubMed Elias CF, Lee C, Kelly J, Aschkenasi C, Ahima RS, Couceyro PR, et al. Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron. 1998;21(6):1375–85.PubMed
43.
Zurück zum Zitat Rother E, Belgardt BF, Tsaousidou E, Hampel B, Waisman A, Myers Jr MG, et al. Acute selective ablation of rat insulin promoter-expressing (RIPHER) neurons defines their orexigenic nature. Proc Natl Acad Sci U S A. 2012;109(44):18132–7.PubMed Rother E, Belgardt BF, Tsaousidou E, Hampel B, Waisman A, Myers Jr MG, et al. Acute selective ablation of rat insulin promoter-expressing (RIPHER) neurons defines their orexigenic nature. Proc Natl Acad Sci U S A. 2012;109(44):18132–7.PubMed
44.
Zurück zum Zitat Zhan C, Zhou J, Feng Q, Zhang JE, Lin S, Bao J, et al. Acute and long-term suppression of feeding behavior by pomc neurons in the brainstem and hypothalamus. Respectively J Neurosci. 2013;33(8):3624–32. Zhan C, Zhou J, Feng Q, Zhang JE, Lin S, Bao J, et al. Acute and long-term suppression of feeding behavior by pomc neurons in the brainstem and hypothalamus. Respectively J Neurosci. 2013;33(8):3624–32.
45.
Zurück zum Zitat Aponte Y, Atasoy D, Sternson SM. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat Neurosci. 2011;14(3):351–5.PubMed Aponte Y, Atasoy D, Sternson SM. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat Neurosci. 2011;14(3):351–5.PubMed
46.
Zurück zum Zitat Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature. 1997;385(6612):165–8.PubMed Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature. 1997;385(6612):165–8.PubMed
47.
Zurück zum Zitat Vaisse C, Clement K, Guy-Grand B, Froguel P. A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat Genet. 1998;20(2):113–4.PubMed Vaisse C, Clement K, Guy-Grand B, Froguel P. A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat Genet. 1998;20(2):113–4.PubMed
48.
Zurück zum Zitat Chen AS, Marsh DJ, Trumbauer ME, Frazier EG, Guan XM, Yu H, et al. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat Genet. 2000;26(1):97–102.PubMed Chen AS, Marsh DJ, Trumbauer ME, Frazier EG, Guan XM, Yu H, et al. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat Genet. 2000;26(1):97–102.PubMed
49.
Zurück zum Zitat Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell. 1997;88(1):131–41.PubMed Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell. 1997;88(1):131–41.PubMed
50.
Zurück zum Zitat Kristensen P, Judge ME, Thim L, Ribel U, Christjansen KN, Wulff BS, et al. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature. 1998;393(6680):72–6.PubMed Kristensen P, Judge ME, Thim L, Ribel U, Christjansen KN, Wulff BS, et al. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature. 1998;393(6680):72–6.PubMed
51.
Zurück zum Zitat Lambert PD, Couceyro PR, McGirr KM, Dall Vechia SE, Smith Y, Kuhar MJ. CART peptides in the central control of feeding and interactions with neuropeptide Y. Synapse. 1998;29(4):293–8.PubMed Lambert PD, Couceyro PR, McGirr KM, Dall Vechia SE, Smith Y, Kuhar MJ. CART peptides in the central control of feeding and interactions with neuropeptide Y. Synapse. 1998;29(4):293–8.PubMed
52.
Zurück zum Zitat Balthasar N, Dalgaard LT, Lee CE, Yu J, Funahashi H, Williams T, et al. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell. 2005;123(3):493–505.PubMed Balthasar N, Dalgaard LT, Lee CE, Yu J, Funahashi H, Williams T, et al. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell. 2005;123(3):493–505.PubMed
53.
Zurück zum Zitat Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR, et al. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci. 2003;6(7):736–42.PubMed Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR, et al. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci. 2003;6(7):736–42.PubMed
54.
Zurück zum Zitat Zheng H, Patterson LM, Rhodes CJ, Louis GW, Skibicka KP, Grill HJ, et al. A potential role for hypothalamomedullary POMC projections in leptin-induced suppression of food intake. Am J Physiol Regul Integr Comp Physiol. 2010;298(3):R720–8.PubMed Zheng H, Patterson LM, Rhodes CJ, Louis GW, Skibicka KP, Grill HJ, et al. A potential role for hypothalamomedullary POMC projections in leptin-induced suppression of food intake. Am J Physiol Regul Integr Comp Physiol. 2010;298(3):R720–8.PubMed
55.
Zurück zum Zitat Parton LE, Ye CP, Coppari R, Enriori PJ, Choi B, Zhang CY, et al. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature. 2007;449(7159):228–32.PubMed Parton LE, Ye CP, Coppari R, Enriori PJ, Choi B, Zhang CY, et al. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature. 2007;449(7159):228–32.PubMed
56.
Zurück zum Zitat Heisler LK, Cowley MA, Tecott LH, Fan W, Low MJ, Smart JL, et al. Activation of central melanocortin pathways by fenfluramine. Science. 2002;297(5581):609–11.PubMed Heisler LK, Cowley MA, Tecott LH, Fan W, Low MJ, Smart JL, et al. Activation of central melanocortin pathways by fenfluramine. Science. 2002;297(5581):609–11.PubMed
57.
Zurück zum Zitat Tecott LH, Sun LM, Akana SF, Strack AM, Lowenstein DH, Dallman MF, et al. Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature. 1995;374(6522):542–6.PubMed Tecott LH, Sun LM, Akana SF, Strack AM, Lowenstein DH, Dallman MF, et al. Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature. 1995;374(6522):542–6.PubMed
58.
Zurück zum Zitat Nonogaki K, Strack AM, Dallman MF, Tecott LH. Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat Med. 1998;4(10):1152–6.PubMed Nonogaki K, Strack AM, Dallman MF, Tecott LH. Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat Med. 1998;4(10):1152–6.PubMed
59.
Zurück zum Zitat Xu Y, Jones JE, Kohno D, Williams KW, Lee CE, Choi MJ, et al. 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis. Neuron. 2008;60(4):582–9. Xu Y, Jones JE, Kohno D, Williams KW, Lee CE, Choi MJ, et al. 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis. Neuron. 2008;60(4):582–9.
60.
Zurück zum Zitat Plum L, Ma X, Hampel B, Balthasar N, Coppari R, Munzberg H, et al. Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. J Clin Invest. 2006;116(7):1886–901.PubMed Plum L, Ma X, Hampel B, Balthasar N, Coppari R, Munzberg H, et al. Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. J Clin Invest. 2006;116(7):1886–901.PubMed
61.
Zurück zum Zitat Sohn JW, Xu Y, Jones JE, Wickman K, Williams KW, Elmquist JK. Serotonin 2C receptor activates a distinct population of arcuate pro-opiomelanocortin neurons via TRPC channels. Neuron. 2011;71(3):488–97.PubMed Sohn JW, Xu Y, Jones JE, Wickman K, Williams KW, Elmquist JK. Serotonin 2C receptor activates a distinct population of arcuate pro-opiomelanocortin neurons via TRPC channels. Neuron. 2011;71(3):488–97.PubMed
62.
Zurück zum Zitat Qiu J, Fang Y, Ronnekleiv OK, Kelly MJ. Leptin excites proopiomelanocortin neurons via activation of TRPC channels. J Neurosci. 2010;30(4):1560–5.PubMed Qiu J, Fang Y, Ronnekleiv OK, Kelly MJ. Leptin excites proopiomelanocortin neurons via activation of TRPC channels. J Neurosci. 2010;30(4):1560–5.PubMed
63.
Zurück zum Zitat Pinto S, Roseberry AG, Liu H, Diano S, Shanabrough M, Cai X, et al. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science. 2004;304(5667):110–5.PubMed Pinto S, Roseberry AG, Liu H, Diano S, Shanabrough M, Cai X, et al. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science. 2004;304(5667):110–5.PubMed
64.
Zurück zum Zitat Vong L, Ye C, Yang Z, Choi B, Chua Jr S, Lowell BB. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron. 2011;71(1):142–54.PubMed Vong L, Ye C, Yang Z, Choi B, Chua Jr S, Lowell BB. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron. 2011;71(1):142–54.PubMed
65.
Zurück zum Zitat Cowley MA, Smart JL, Rubinstein M, Cerdan MG, Diano S, Horvath TL, et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature. 2001;411(6836):480–4.PubMed Cowley MA, Smart JL, Rubinstein M, Cerdan MG, Diano S, Horvath TL, et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature. 2001;411(6836):480–4.PubMed
66.
Zurück zum Zitat Sternson SM, Shepherd GM, Friedman JM. Topographic mapping of VMH – arcuate nucleus microcircuits and their reorganization by fasting. Nat Neurosci. 2005;8(10):1356–63.PubMed Sternson SM, Shepherd GM, Friedman JM. Topographic mapping of VMH – arcuate nucleus microcircuits and their reorganization by fasting. Nat Neurosci. 2005;8(10):1356–63.PubMed
67.
Zurück zum Zitat Xu Y, Berglund ED, Sohn JW, Holland WL, Chuang JC, Fukuda M, et al. 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate insulin sensitivity in liver. Nat Neurosci. 2010;13(12):1457–9.PubMed Xu Y, Berglund ED, Sohn JW, Holland WL, Chuang JC, Fukuda M, et al. 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate insulin sensitivity in liver. Nat Neurosci. 2010;13(12):1457–9.PubMed
68.
Zurück zum Zitat Xu AW, Ste-Marie L, Kaelin CB, Barsh GS. Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding. Endocrinology. 2007;148(1):72–80.PubMed Xu AW, Ste-Marie L, Kaelin CB, Barsh GS. Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding. Endocrinology. 2007;148(1):72–80.PubMed
69.
Zurück zum Zitat Al-Qassab H, Smith MA, Irvine EE, Guillermet-Guibert J, Claret M, Choudhury AI, et al. Dominant role of the p110beta isoform of PI3K over p110alpha in energy homeostasis regulation by POMC and AgRP neurons. Cell Metab. 2009;10(5):343–54.PubMed Al-Qassab H, Smith MA, Irvine EE, Guillermet-Guibert J, Claret M, Choudhury AI, et al. Dominant role of the p110beta isoform of PI3K over p110alpha in energy homeostasis regulation by POMC and AgRP neurons. Cell Metab. 2009;10(5):343–54.PubMed
70.
Zurück zum Zitat Claret M, Smith MA, Batterham RL, Selman C, Choudhury AI, Fryer LG, et al. AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J Clin Invest. 2007;117(8):2325–36.PubMed Claret M, Smith MA, Batterham RL, Selman C, Choudhury AI, Fryer LG, et al. AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J Clin Invest. 2007;117(8):2325–36.PubMed
71.
Zurück zum Zitat Claret M, Smith MA, Knauf C, Al-Qassab H, Woods A, Heslegrave A, et al. Deletion of Lkb1 in pro-opiomelanocortin neurons impairs peripheral glucose homeostasis in mice. Diabetes. 2011;60(3):735–45.PubMed Claret M, Smith MA, Knauf C, Al-Qassab H, Woods A, Heslegrave A, et al. Deletion of Lkb1 in pro-opiomelanocortin neurons impairs peripheral glucose homeostasis in mice. Diabetes. 2011;60(3):735–45.PubMed
72.
Zurück zum Zitat Yang SB, Tien AC, Boddupalli G, Xu AW, Jan YN, Jan LY. Rapamycin ameliorates age-dependent obesity associated with increased mTOR signaling in hypothalamic POMC neurons. Neuron. 2012;75(3):425–36.PubMed Yang SB, Tien AC, Boddupalli G, Xu AW, Jan YN, Jan LY. Rapamycin ameliorates age-dependent obesity associated with increased mTOR signaling in hypothalamic POMC neurons. Neuron. 2012;75(3):425–36.PubMed
73.
Zurück zum Zitat Mori H, Inoki K, Munzberg H, Opland D, Faouzi M, Villanueva EC, et al. Critical role for hypothalamic mTOR activity in energy balance. Cell Metab. 2009;9(4):362–74.PubMed Mori H, Inoki K, Munzberg H, Opland D, Faouzi M, Villanueva EC, et al. Critical role for hypothalamic mTOR activity in energy balance. Cell Metab. 2009;9(4):362–74.PubMed
74.
Zurück zum Zitat Diano S, Liu ZW, Jeong JK, Dietrich MO, Ruan HB, Kim E, et al. Peroxisome proliferation-associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity. Nat Med. 2011;17(9):1121–7.PubMed Diano S, Liu ZW, Jeong JK, Dietrich MO, Ruan HB, Kim E, et al. Peroxisome proliferation-associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity. Nat Med. 2011;17(9):1121–7.PubMed
75.
Zurück zum Zitat Quan W, Kim HK, Moon EY, Kim SS, Choi CS, Komatsu M, et al. Role of hypothalamic proopiomelanocortin neuron autophagy in the control of appetite and leptin response. Endocrinology. 2012;153(4):1817–26.PubMed Quan W, Kim HK, Moon EY, Kim SS, Choi CS, Komatsu M, et al. Role of hypothalamic proopiomelanocortin neuron autophagy in the control of appetite and leptin response. Endocrinology. 2012;153(4):1817–26.PubMed
76.
Zurück zum Zitat Coupe B, Ishii Y, Dietrich MO, Komatsu M, Horvath TL, Bouret SG. Loss of autophagy in pro-opiomelanocortin neurons perturbs axon growth and causes metabolic dysregulation. Cell Metab. 2012;15(2):247–55.PubMed Coupe B, Ishii Y, Dietrich MO, Komatsu M, Horvath TL, Bouret SG. Loss of autophagy in pro-opiomelanocortin neurons perturbs axon growth and causes metabolic dysregulation. Cell Metab. 2012;15(2):247–55.PubMed
77.
Zurück zum Zitat Kaushik S, Arias E, Kwon H, Lopez NM, Athonvarangkul D, Sahu S, et al. Loss of autophagy in hypothalamic POMC neurons impairs lipolysis. EMBO reports. 2012;13(3):258–65.PubMed Kaushik S, Arias E, Kwon H, Lopez NM, Athonvarangkul D, Sahu S, et al. Loss of autophagy in hypothalamic POMC neurons impairs lipolysis. EMBO reports. 2012;13(3):258–65.PubMed
78.
Zurück zum Zitat Williams KW, Margatho LO, Lee CE, Choi M, Lee S, Scott MM, et al. Segregation of acute leptin and insulin effects in distinct populations of arcuate proopiomelanocortin neurons. J Neurosci. 2010;30(7):2472–9.PubMed Williams KW, Margatho LO, Lee CE, Choi M, Lee S, Scott MM, et al. Segregation of acute leptin and insulin effects in distinct populations of arcuate proopiomelanocortin neurons. J Neurosci. 2010;30(7):2472–9.PubMed
79.
Zurück zum Zitat Hahn TM, Breininger JF, Baskin DG, Schwartz MW. Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nat Neurosci. 1998;1(4):271–2.PubMed Hahn TM, Breininger JF, Baskin DG, Schwartz MW. Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nat Neurosci. 1998;1(4):271–2.PubMed
80.
Zurück zum Zitat Krashes MJ, Koda S, Ye C, Rogan SC, Adams AC, Cusher DS, et al. Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J Clin Invest. 2011;121(4):1424–8.PubMed Krashes MJ, Koda S, Ye C, Rogan SC, Adams AC, Cusher DS, et al. Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J Clin Invest. 2011;121(4):1424–8.PubMed
81.
Zurück zum Zitat Luquet S, Perez FA, Hnasko TS, Palmiter RD. NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates. Science. 2005;310(5748):683–5.PubMed Luquet S, Perez FA, Hnasko TS, Palmiter RD. NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates. Science. 2005;310(5748):683–5.PubMed
82.
Zurück zum Zitat Gropp E, Shanabrough M, Borok E, Xu AW, Janoschek R, Buch T, et al. Agouti-related peptide-expressing neurons are mandatory for feeding. Nat Neurosci. 2005;8(10):1289–91.PubMed Gropp E, Shanabrough M, Borok E, Xu AW, Janoschek R, Buch T, et al. Agouti-related peptide-expressing neurons are mandatory for feeding. Nat Neurosci. 2005;8(10):1289–91.PubMed
83.
Zurück zum Zitat Ollmann MM, Wilson BD, Yang YK, Kerns JA, Chen Y, Gantz I, et al. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science. 1997;278(5335):135–8PubMed Ollmann MM, Wilson BD, Yang YK, Kerns JA, Chen Y, Gantz I, et al. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science. 1997;278(5335):135–8PubMed
84.
Zurück zum Zitat Tong Q, Ye CP, Jones JE, Elmquist JK, Lowell BB. Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance. Nat Neurosci. 2008;11(9):998–1000.PubMed Tong Q, Ye CP, Jones JE, Elmquist JK, Lowell BB. Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance. Nat Neurosci. 2008;11(9):998–1000.PubMed
85.
Zurück zum Zitat Atasoy D, Betley JN, Su HH, Sternson SM. Deconstruction of a neural circuit for hunger. Nature. 2012;488(7410):172–7.PubMed Atasoy D, Betley JN, Su HH, Sternson SM. Deconstruction of a neural circuit for hunger. Nature. 2012;488(7410):172–7.PubMed
86.
Zurück zum Zitat Marsh DJ, Hollopeter G, Kafer KE, Palmiter RD. Role of the Y5 neuropeptide Y receptor in feeding and obesity. Nat Med. 1998;4(6):718–21.PubMed Marsh DJ, Hollopeter G, Kafer KE, Palmiter RD. Role of the Y5 neuropeptide Y receptor in feeding and obesity. Nat Med. 1998;4(6):718–21.PubMed
87.
Zurück zum Zitat Kushi A, Sasai H, Koizumi H, Takeda N, Yokoyama M, Nakamura M. Obesity and mild hyperinsulinemia found in neuropeptide Y-Y1 receptor-deficient mice. Proc Natl Acad Sci U S A. 1998;95(26):15659–64.PubMed Kushi A, Sasai H, Koizumi H, Takeda N, Yokoyama M, Nakamura M. Obesity and mild hyperinsulinemia found in neuropeptide Y-Y1 receptor-deficient mice. Proc Natl Acad Sci U S A. 1998;95(26):15659–64.PubMed
88.
Zurück zum Zitat Nguyen AD, Mitchell NF, Lin S, Macia L, Yulyaningsih E, Baldock PA, et al. Y1 and Y5 receptors are both required for the regulation of food intake and energy homeostasis in mice. PLoS One. 2012;7(6):e40191.PubMed Nguyen AD, Mitchell NF, Lin S, Macia L, Yulyaningsih E, Baldock PA, et al. Y1 and Y5 receptors are both required for the regulation of food intake and energy homeostasis in mice. PLoS One. 2012;7(6):e40191.PubMed
89.
Zurück zum Zitat Erickson JC, Clegg KE, Palmiter RD. Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y. Nature. 1996;381(6581):415–21.PubMed Erickson JC, Clegg KE, Palmiter RD. Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y. Nature. 1996;381(6581):415–21.PubMed
90.
Zurück zum Zitat Wu Q, Boyle MP, Palmiter RD. Loss of GABAergic signaling by AgRP neurons to the parabrachial nucleus leads to starvation. Cell. 2009;137(7):1225–34.PubMed Wu Q, Boyle MP, Palmiter RD. Loss of GABAergic signaling by AgRP neurons to the parabrachial nucleus leads to starvation. Cell. 2009;137(7):1225–34.PubMed
91.
Zurück zum Zitat Liu T, Kong D, Shah BP, Ye C, Koda S, Saunders A, et al. Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone. Neuron. 2012;73(3):511–22.PubMed Liu T, Kong D, Shah BP, Ye C, Koda S, Saunders A, et al. Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone. Neuron. 2012;73(3):511–22.PubMed
92.
Zurück zum Zitat Yang Y, Atasoy D, Su HH, Sternson SM. Hunger states switch a flip-flop memory circuit via a synaptic AMPK-dependent positive feedback loop. Cell. 2011;146(6):992–1003.PubMed Yang Y, Atasoy D, Su HH, Sternson SM. Hunger states switch a flip-flop memory circuit via a synaptic AMPK-dependent positive feedback loop. Cell. 2011;146(6):992–1003.PubMed
93.
Zurück zum Zitat Ren H, Orozco IJ, Su Y, Suyama S, Gutierrez-Juarez R, Horvath TL, et al. FoxO1 target Gpr17 activates AgRP neurons to regulate food intake. Cell. 2012;149(6):1314–26.PubMed Ren H, Orozco IJ, Su Y, Suyama S, Gutierrez-Juarez R, Horvath TL, et al. FoxO1 target Gpr17 activates AgRP neurons to regulate food intake. Cell. 2012;149(6):1314–26.PubMed
94.
Zurück zum Zitat Anderson KA, Ribar TJ, Lin F, Noeldner PK, Green MF, Muehlbauer MJ, et al. Hypothalamic CaMKK2 contributes to the regulation of energy balance. Cell Metab. 2008;7(5):377–88.PubMed Anderson KA, Ribar TJ, Lin F, Noeldner PK, Green MF, Muehlbauer MJ, et al. Hypothalamic CaMKK2 contributes to the regulation of energy balance. Cell Metab. 2008;7(5):377–88.PubMed
95.
Zurück zum Zitat Andrews ZB, Liu ZW, Walllingford N, Erion DM, Borok E, Friedman JM, et al. UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals. Nature. 2008;454(7206):846–51.PubMed Andrews ZB, Liu ZW, Walllingford N, Erion DM, Borok E, Friedman JM, et al. UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals. Nature. 2008;454(7206):846–51.PubMed
96.
Zurück zum Zitat Coppola A, Liu ZW, Andrews ZB, Paradis E, Roy MC, Friedman JM, et al. A central thermogenic-like mechanism in feeding regulation: an interplay between arcuate nucleus T3 and UCP2. Cell Metab. 2007;5(1):21–33.PubMed Coppola A, Liu ZW, Andrews ZB, Paradis E, Roy MC, Friedman JM, et al. A central thermogenic-like mechanism in feeding regulation: an interplay between arcuate nucleus T3 and UCP2. Cell Metab. 2007;5(1):21–33.PubMed
97.
Zurück zum Zitat Kaushik S, Rodriguez-Navarro JA, Arias E, Kiffin R, Sahu S, Schwartz GJ, et al. Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance. Cell Metab. 2011;14(2):173–83.PubMed Kaushik S, Rodriguez-Navarro JA, Arias E, Kiffin R, Sahu S, Schwartz GJ, et al. Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance. Cell Metab. 2011;14(2):173–83.PubMed
98.
Zurück zum Zitat Lin X, Taguchi A, Park S, Kushner JA, Li F, Li Y, et al. Dysregulation of insulin receptor substrate 2 in beta cells and brain causes obesity and diabetes. J Clin Invest. 2004;114(7):908–16.PubMed Lin X, Taguchi A, Park S, Kushner JA, Li F, Li Y, et al. Dysregulation of insulin receptor substrate 2 in beta cells and brain causes obesity and diabetes. J Clin Invest. 2004;114(7):908–16.PubMed
99.
Zurück zum Zitat Choudhury AI, Heffron H, Smith MA, Al-Qassab H, Xu AW, Selman C, et al. The role of insulin receptor substrate 2 in hypothalamic and beta cell function. The Journal Of Clinical Investigation. 2005;115(4):940–50.PubMed Choudhury AI, Heffron H, Smith MA, Al-Qassab H, Xu AW, Selman C, et al. The role of insulin receptor substrate 2 in hypothalamic and beta cell function. The Journal Of Clinical Investigation. 2005;115(4):940–50.PubMed
100.
Zurück zum Zitat Cui Y, Huang L, Elefteriou F, Yang G, Shelton JM, Giles JE, et al. Essential role of STAT3 in body weight and glucose homeostasis. Mol Cell Biol. 2004;24(1):258–69.PubMed Cui Y, Huang L, Elefteriou F, Yang G, Shelton JM, Giles JE, et al. Essential role of STAT3 in body weight and glucose homeostasis. Mol Cell Biol. 2004;24(1):258–69.PubMed
101.
Zurück zum Zitat Majdic G, Young M, Gomez-Sanchez E, Anderson P, Szczepaniak LS, Dobbins RL, et al. Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity. Endocrinology. 2002;143(2):607–14.PubMed Majdic G, Young M, Gomez-Sanchez E, Anderson P, Szczepaniak LS, Dobbins RL, et al. Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity. Endocrinology. 2002;143(2):607–14.PubMed
102.
Zurück zum Zitat Kim KW, Zhao L, Donato Jr J, Kohno D, Xu Y, Elias CF, et al. Steroidogenic factor 1 directs programs regulating diet-induced thermogenesis and leptin action in the ventral medial hypothalamic nucleus. Proc Natl Acad Sci U S A. 2011;108(26):10673–8.PubMed Kim KW, Zhao L, Donato Jr J, Kohno D, Xu Y, Elias CF, et al. Steroidogenic factor 1 directs programs regulating diet-induced thermogenesis and leptin action in the ventral medial hypothalamic nucleus. Proc Natl Acad Sci U S A. 2011;108(26):10673–8.PubMed
103.
Zurück zum Zitat Dhillon H, Zigman JM, Ye C, Lee CE, McGovern RA, Tang V, et al. Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron. 2006;49(2):191–203.PubMed Dhillon H, Zigman JM, Ye C, Lee CE, McGovern RA, Tang V, et al. Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron. 2006;49(2):191–203.PubMed
104.
Zurück zum Zitat Ramadori G, Fujikawa T, Anderson J, Berglund ED, Frazao R, Michan S, et al. SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance. Cell Metab. 2011;14(3):301–12.PubMed Ramadori G, Fujikawa T, Anderson J, Berglund ED, Frazao R, Michan S, et al. SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance. Cell Metab. 2011;14(3):301–12.PubMed
105.
Zurück zum Zitat Chao H, Digruccio M, Chen P, Li C. Type 2 corticotropin-releasing factor receptor in the ventromedial nucleus of hypothalamus is critical in regulating feeding and lipid metabolism in white adipose tissue. Endocrinology. 2012;153(1):166–76.PubMed Chao H, Digruccio M, Chen P, Li C. Type 2 corticotropin-releasing factor receptor in the ventromedial nucleus of hypothalamus is critical in regulating feeding and lipid metabolism in white adipose tissue. Endocrinology. 2012;153(1):166–76.PubMed
106.
Zurück zum Zitat Tong Q, Ye C, McCrimmon RJ, Dhillon H, Choi B, Kramer MD, et al. Synaptic glutamate release by ventromedial hypothalamic neurons is part of the neurocircuitry that prevents hypoglycemia. Cell Metab. 2007;5(5):383–93.PubMed Tong Q, Ye C, McCrimmon RJ, Dhillon H, Choi B, Kramer MD, et al. Synaptic glutamate release by ventromedial hypothalamic neurons is part of the neurocircuitry that prevents hypoglycemia. Cell Metab. 2007;5(5):383–93.PubMed
107.
Zurück zum Zitat Cordeira J, Rios M. Weighing in the role of BDNF in the central control of eating behavior. Mol Neurobiol. 2011;44(3):441–8.PubMed Cordeira J, Rios M. Weighing in the role of BDNF in the central control of eating behavior. Mol Neurobiol. 2011;44(3):441–8.PubMed
108.
Zurück zum Zitat Noble EE, Billington CJ, Kotz CM, Wang C. The lighter side of BDNF. Am J Physiol Regul Integr Comp Physiol. 2011;300(5):R1053–69.PubMed Noble EE, Billington CJ, Kotz CM, Wang C. The lighter side of BDNF. Am J Physiol Regul Integr Comp Physiol. 2011;300(5):R1053–69.PubMed
109.
Zurück zum Zitat Kernie SG, Liebl DJ, Parada LF. BDNF regulates eating behavior and locomotor activity in mice. Embo J. 2000;19(6):1290–300.PubMed Kernie SG, Liebl DJ, Parada LF. BDNF regulates eating behavior and locomotor activity in mice. Embo J. 2000;19(6):1290–300.PubMed
110.
Zurück zum Zitat Wang C, Bomberg E, Billington C, Levine A, Kotz CM. Brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus increases energy expenditure by elevating metabolic rate. Am J Physiol Regul Integr Comp Physiol. 2007;293(3):R992–R1002.PubMed Wang C, Bomberg E, Billington C, Levine A, Kotz CM. Brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus increases energy expenditure by elevating metabolic rate. Am J Physiol Regul Integr Comp Physiol. 2007;293(3):R992–R1002.PubMed
111.
Zurück zum Zitat Wang C, Bomberg E, Levine A, Billington C, Kotz CM. Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake. Am J Physiol Regul Integr Comp Physiol. 2007;293(3):R1037–45.PubMed Wang C, Bomberg E, Levine A, Billington C, Kotz CM. Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake. Am J Physiol Regul Integr Comp Physiol. 2007;293(3):R1037–45.PubMed
112.
Zurück zum Zitat Wang C, Godar RJ, Billington CJ, Kotz CM. Chronic administration of brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus reverses obesity induced by high-fat diet. Am J Physiol Regul Integr Comp Physiol. 2010;298(5):R1320–32.PubMed Wang C, Godar RJ, Billington CJ, Kotz CM. Chronic administration of brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus reverses obesity induced by high-fat diet. Am J Physiol Regul Integr Comp Physiol. 2010;298(5):R1320–32.PubMed
113.
Zurück zum Zitat Jeanneteau FD, Lambert WM, Ismaili N, Bath KG, Lee FS, Garabedian MJ, et al. BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus. Proc Natl Acad Sci U S A. 2012;109(4):1305–10.PubMed Jeanneteau FD, Lambert WM, Ismaili N, Bath KG, Lee FS, Garabedian MJ, et al. BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus. Proc Natl Acad Sci U S A. 2012;109(4):1305–10.PubMed
114.
Zurück zum Zitat Toriya M, Maekawa F, Maejima Y, Onaka T, Fujiwara K, Nakagawa T, et al. Long-term infusion of brain-derived neurotrophic factor reduces food intake and body weight via a corticotrophin-releasing hormone pathway in the paraventricular nucleus of the hypothalamus. J Neuroendocrinol. 2010;22(9):987–95.PubMed Toriya M, Maekawa F, Maejima Y, Onaka T, Fujiwara K, Nakagawa T, et al. Long-term infusion of brain-derived neurotrophic factor reduces food intake and body weight via a corticotrophin-releasing hormone pathway in the paraventricular nucleus of the hypothalamus. J Neuroendocrinol. 2010;22(9):987–95.PubMed
115.
Zurück zum Zitat Liao GY, An JJ, Gharami K, Waterhouse EG, Vanevski F, Jones KR, et al. Dendritically targeted Bdnf mRNA is essential for energy balance and response to leptin. Nat Med. 2012;18(4):564–71.PubMed Liao GY, An JJ, Gharami K, Waterhouse EG, Vanevski F, Jones KR, et al. Dendritically targeted Bdnf mRNA is essential for energy balance and response to leptin. Nat Med. 2012;18(4):564–71.PubMed
116.
Zurück zum Zitat Hawke Z, Ivanov TR, Bechtold DA, Dhillon H, Lowell BB, Luckman SM. PACAP neurons in the hypothalamic ventromedial nucleus are targets of central leptin signaling. J Neurosci. 2009;29(47):14828–35.PubMed Hawke Z, Ivanov TR, Bechtold DA, Dhillon H, Lowell BB, Luckman SM. PACAP neurons in the hypothalamic ventromedial nucleus are targets of central leptin signaling. J Neurosci. 2009;29(47):14828–35.PubMed
117.
Zurück zum Zitat Guan XM, Yu H, Trumbauer M, Frazier E, Van der Ploeg LH, Chen H. Induction of neuropeptide Y expression in dorsomedial hypothalamus of diet-induced obese mice. Neuroreport. 1998;9(15):3415–9.PubMed Guan XM, Yu H, Trumbauer M, Frazier E, Van der Ploeg LH, Chen H. Induction of neuropeptide Y expression in dorsomedial hypothalamus of diet-induced obese mice. Neuroreport. 1998;9(15):3415–9.PubMed
118.
Zurück zum Zitat Lee SJ, Kirigiti M, Lindsley SR, Loche A, Madden CJ, Morrison SF, et al. Efferent projections of NPY expressing neurons of the dorsomedial hypothalamus in chronic hyperphagic models. J Comp Neurol. 2013;521(8)1891–914. Lee SJ, Kirigiti M, Lindsley SR, Loche A, Madden CJ, Morrison SF, et al. Efferent projections of NPY expressing neurons of the dorsomedial hypothalamus in chronic hyperphagic models. J Comp Neurol. 2013;521(8)1891–914.
119.
Zurück zum Zitat Bi S, Kim YJ, Zheng F. Dorsomedial hypothalamic NPY and energy balance control. Neuropeptides. 2012;46(6):309–14.PubMed Bi S, Kim YJ, Zheng F. Dorsomedial hypothalamic NPY and energy balance control. Neuropeptides. 2012;46(6):309–14.PubMed
120.
Zurück zum Zitat Bi S, Robinson BM, Moran TH. Acute food deprivation and chronic food restriction differentially affect hypothalamic NPY mRNA expression. Am J Physiol Regul Integr Comp Physiol. 2003;285(5):R1030–6.PubMed Bi S, Robinson BM, Moran TH. Acute food deprivation and chronic food restriction differentially affect hypothalamic NPY mRNA expression. Am J Physiol Regul Integr Comp Physiol. 2003;285(5):R1030–6.PubMed
121.
Zurück zum Zitat Yang L, Scott KA, Hyun J, Tamashiro KL, Tray N, Moran TH, et al. Role of dorsomedial hypothalamic neuropeptide Y in modulating food intake and energy balance. J Neurosci. 2009;29(1):179–90.PubMed Yang L, Scott KA, Hyun J, Tamashiro KL, Tray N, Moran TH, et al. Role of dorsomedial hypothalamic neuropeptide Y in modulating food intake and energy balance. J Neurosci. 2009;29(1):179–90.PubMed
122.
Zurück zum Zitat Bi S, Scott KA, Kopin AS, Moran TH. Differential roles for cholecystokinin a receptors in energy balance in rats and mice. Endocrinology. 2004;145(8):3873–80.PubMed Bi S, Scott KA, Kopin AS, Moran TH. Differential roles for cholecystokinin a receptors in energy balance in rats and mice. Endocrinology. 2004;145(8):3873–80.PubMed
123.
Zurück zum Zitat Leibowitz SF, Hammer NJ, Chang K. Hypothalamic paraventricular nucleus lesions produce overeating and obesity in the rat. Physiol Behav. 1981;27(6):1031–40.PubMed Leibowitz SF, Hammer NJ, Chang K. Hypothalamic paraventricular nucleus lesions produce overeating and obesity in the rat. Physiol Behav. 1981;27(6):1031–40.PubMed
124.
Zurück zum Zitat Xi D, Gandhi N, Lai M, Kublaoui BM. Ablation of Sim1 neurons causes obesity through hyperphagia and reduced energy expenditure. PLoS One. 2012;7(4):e36453. Xi D, Gandhi N, Lai M, Kublaoui BM. Ablation of Sim1 neurons causes obesity through hyperphagia and reduced energy expenditure. PLoS One. 2012;7(4):e36453.
125.
Zurück zum Zitat Tolson KP, Gemelli T, Gautron L, Elmquist JK, Zinn AR, Kublaoui BM. Postnatal Sim1 deficiency causes hyperphagic obesity and reduced Mc4r and oxytocin expression. J Neurosci. 2010;30(10):3803–12.PubMed Tolson KP, Gemelli T, Gautron L, Elmquist JK, Zinn AR, Kublaoui BM. Postnatal Sim1 deficiency causes hyperphagic obesity and reduced Mc4r and oxytocin expression. J Neurosci. 2010;30(10):3803–12.PubMed
126.
Zurück zum Zitat Cone RD. Anatomy and regulation of the central melanocortin system. Nat Neurosci. 2005;8(5):571–8.PubMed Cone RD. Anatomy and regulation of the central melanocortin system. Nat Neurosci. 2005;8(5):571–8.PubMed
127.
Zurück zum Zitat Kalsbeek A, La Fleur S, Van Heijningen C, Buijs RM. Suprachiasmatic GABAergic inputs to the paraventricular nucleus control plasma glucose concentrations in the rat via sympathetic innervation of the liver. J Neurosci. 2004;24(35):7604–13.PubMed Kalsbeek A, La Fleur S, Van Heijningen C, Buijs RM. Suprachiasmatic GABAergic inputs to the paraventricular nucleus control plasma glucose concentrations in the rat via sympathetic innervation of the liver. J Neurosci. 2004;24(35):7604–13.PubMed
128.
Zurück zum Zitat Ma X, Zubcevic L, Bruning JC, Ashcroft FM, Burdakov D. Electrical inhibition of identified anorexigenic POMC neurons by orexin/hypocretin. J Neurosci. 2007;27(7):1529–33.PubMed Ma X, Zubcevic L, Bruning JC, Ashcroft FM, Burdakov D. Electrical inhibition of identified anorexigenic POMC neurons by orexin/hypocretin. J Neurosci. 2007;27(7):1529–33.PubMed
129.
Zurück zum Zitat Gotoh K, Fukagawa K, Fukagawa T, Noguchi H, Kakuma T, Sakata T, et al. Hypothalamic neuronal histamine mediates the thyrotropin-releasing hormone-induced suppression of food intake. J Neurochem. 2007;103(3):1102–10.PubMed Gotoh K, Fukagawa K, Fukagawa T, Noguchi H, Kakuma T, Sakata T, et al. Hypothalamic neuronal histamine mediates the thyrotropin-releasing hormone-induced suppression of food intake. J Neurochem. 2007;103(3):1102–10.PubMed
130.
Zurück zum Zitat Zhang X, van den Pol AN. Thyrotropin-releasing hormone (TRH) inhibits melanin-concentrating hormone neurons: implications for TRH-mediated anorexic and arousal actions. J Neurosci. 2012;32(9):3032–43.PubMed Zhang X, van den Pol AN. Thyrotropin-releasing hormone (TRH) inhibits melanin-concentrating hormone neurons: implications for TRH-mediated anorexic and arousal actions. J Neurosci. 2012;32(9):3032–43.PubMed
131.
Zurück zum Zitat Sarvari A, Farkas E, Kadar A, Zseli G, Fuzesi T, Lechan RM, et al. Thyrotropin-releasing hormone-containing axons innervate histaminergic neurons in the tuberomammillary nucleus. Brain Res. 2012;1488:72–80.PubMed Sarvari A, Farkas E, Kadar A, Zseli G, Fuzesi T, Lechan RM, et al. Thyrotropin-releasing hormone-containing axons innervate histaminergic neurons in the tuberomammillary nucleus. Brain Res. 2012;1488:72–80.PubMed
132.
Zurück zum Zitat Parmentier R, Kolbaev S, Klyuch BP, Vandael D, Lin JS, Selbach O, et al. Excitation of histaminergic tuberomamillary neurons by thyrotropin-releasing hormone. J Neurosci. 2009;29(14):4471–83.PubMed Parmentier R, Kolbaev S, Klyuch BP, Vandael D, Lin JS, Selbach O, et al. Excitation of histaminergic tuberomamillary neurons by thyrotropin-releasing hormone. J Neurosci. 2009;29(14):4471–83.PubMed
133.
Zurück zum Zitat Takahashi K, Suwa H, Ishikawa T, Kotani H. Targeted disruption of H3 receptors results in changes in brain histamine tone leading to an obese phenotype. J Clin Invest. 2002;110(12):1791–9.PubMed Takahashi K, Suwa H, Ishikawa T, Kotani H. Targeted disruption of H3 receptors results in changes in brain histamine tone leading to an obese phenotype. J Clin Invest. 2002;110(12):1791–9.PubMed
134.
Zurück zum Zitat Masaki T, Chiba S, Yasuda T, Noguchi H, Kakuma T, Watanabe T, et al. Involvement of hypothalamic histamine H1 receptor in the regulation of feeding rhythm and obesity. Diabetes. 2004;53(9):2250–60.PubMed Masaki T, Chiba S, Yasuda T, Noguchi H, Kakuma T, Watanabe T, et al. Involvement of hypothalamic histamine H1 receptor in the regulation of feeding rhythm and obesity. Diabetes. 2004;53(9):2250–60.PubMed
135.
Zurück zum Zitat Hegyi K, Fulop KA, Kovacs KJ, Falus A, Toth S. High leptin level is accompanied with decreased long leptin receptor transcript in histamine deficient transgenic mice. Immunol Lett. 2004;92(1–2):193–7.PubMed Hegyi K, Fulop KA, Kovacs KJ, Falus A, Toth S. High leptin level is accompanied with decreased long leptin receptor transcript in histamine deficient transgenic mice. Immunol Lett. 2004;92(1–2):193–7.PubMed
136.
Zurück zum Zitat Abel ED, Peroni O, Kim JK, Kim YB, Boss O, Hadro E, et al. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature. 2001;409(6821):729–33.PubMed Abel ED, Peroni O, Kim JK, Kim YB, Boss O, Hadro E, et al. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature. 2001;409(6821):729–33.PubMed
137.
Zurück zum Zitat Ghamari-Langroudi M, Vella KR, Srisai D, Sugrue ML, Hollenberg AN, Cone RD. Regulation of thyrotropin-releasing hormone-expressing neurons in paraventricular nucleus of the hypothalamus by signals of adiposity. Mol Endocrinol. 2010;24(12):2366–81.PubMed Ghamari-Langroudi M, Vella KR, Srisai D, Sugrue ML, Hollenberg AN, Cone RD. Regulation of thyrotropin-releasing hormone-expressing neurons in paraventricular nucleus of the hypothalamus by signals of adiposity. Mol Endocrinol. 2010;24(12):2366–81.PubMed
138.
Zurück zum Zitat Fekete C, Legradi G, Mihaly E, Huang QH, Tatro JB, Rand WM, et al. alpha-Melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and prevents fasting-induced suppression of prothyrotropin-releasing hormone gene expression. J Neurosci. 2000;20(4):1550–8.PubMed Fekete C, Legradi G, Mihaly E, Huang QH, Tatro JB, Rand WM, et al. alpha-Melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and prevents fasting-induced suppression of prothyrotropin-releasing hormone gene expression. J Neurosci. 2000;20(4):1550–8.PubMed
139.
Zurück zum Zitat Fekete C, Kelly J, Mihaly E, Sarkar S, Rand WM, Legradi G, et al. Neuropeptide Y has a central inhibitory action on the hypothalamic-pituitary-thyroid axis. Endocrinology. 2001;142(6):2606–13.PubMed Fekete C, Kelly J, Mihaly E, Sarkar S, Rand WM, Legradi G, et al. Neuropeptide Y has a central inhibitory action on the hypothalamic-pituitary-thyroid axis. Endocrinology. 2001;142(6):2606–13.PubMed
140.
Zurück zum Zitat Onaka T, Takayanagi Y, Yoshida M. Roles of oxytocin neurones in the control of stress, energy metabolism, and social behaviour. J Neuroendocrinol. 2012;24(4):587–98.PubMed Onaka T, Takayanagi Y, Yoshida M. Roles of oxytocin neurones in the control of stress, energy metabolism, and social behaviour. J Neuroendocrinol. 2012;24(4):587–98.PubMed
141.
Zurück zum Zitat Zhang G, Bai H, Zhang H, Dean C, Wu Q, Li J, et al. Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance. Neuron. 2011;69(3):523–35.PubMed Zhang G, Bai H, Zhang H, Dean C, Wu Q, Li J, et al. Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance. Neuron. 2011;69(3):523–35.PubMed
142.
Zurück zum Zitat Matarazzo V, Schaller F, Nedelec E, Benani A, Penicaud L, Muscatelli F, et al. Inactivation of Socs3 in the hypothalamus enhances the hindbrain response to endogenous satiety signals via oxytocin signaling. J Neurosci. 2012;32(48):17097–107.PubMed Matarazzo V, Schaller F, Nedelec E, Benani A, Penicaud L, Muscatelli F, et al. Inactivation of Socs3 in the hypothalamus enhances the hindbrain response to endogenous satiety signals via oxytocin signaling. J Neurosci. 2012;32(48):17097–107.PubMed
143.
Zurück zum Zitat Blevins JE, Schwartz MW, Baskin DG. Evidence that paraventricular nucleus oxytocin neurons link hypothalamic leptin action to caudal brain stem nuclei controlling meal size. Am J Physiol Regul Integr Comp Physiol. 2004;287(1):R87–96.PubMed Blevins JE, Schwartz MW, Baskin DG. Evidence that paraventricular nucleus oxytocin neurons link hypothalamic leptin action to caudal brain stem nuclei controlling meal size. Am J Physiol Regul Integr Comp Physiol. 2004;287(1):R87–96.PubMed
144.
Zurück zum Zitat Wu Z, Xu Y, Zhu Y, Sutton AK, Zhao R, Lowell BB, et al. An obligate role of oxytocin neurons in diet induced energy expenditure. PLoS One. 2012;7(9):e45167.PubMed Wu Z, Xu Y, Zhu Y, Sutton AK, Zhao R, Lowell BB, et al. An obligate role of oxytocin neurons in diet induced energy expenditure. PLoS One. 2012;7(9):e45167.PubMed
145.
Zurück zum Zitat Rohner-Jeanrenaud F, Walker CD, Greco-Perotto R, Jeanrenaud B. Central corticotropin-releasing factor administration prevents the excessive body weight gain of genetically obese (fa/fa) rats. Endocrinology. 1989;124(2):733–9.PubMed Rohner-Jeanrenaud F, Walker CD, Greco-Perotto R, Jeanrenaud B. Central corticotropin-releasing factor administration prevents the excessive body weight gain of genetically obese (fa/fa) rats. Endocrinology. 1989;124(2):733–9.PubMed
146.
Zurück zum Zitat Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92(4):573–85.PubMed Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92(4):573–85.PubMed
147.
Zurück zum Zitat de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A. 1998;95(1):322–7.PubMed de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A. 1998;95(1):322–7.PubMed
148.
Zurück zum Zitat Parise EM, Lilly N, Kay K, Dossat AM, Seth R, Overton JM, et al. Evidence for the role of hindbrain orexin-1 receptors in the control of meal size. Am J Physiol Regul Integr Comp Physiol. 2011;301(6):R1692–9.PubMed Parise EM, Lilly N, Kay K, Dossat AM, Seth R, Overton JM, et al. Evidence for the role of hindbrain orexin-1 receptors in the control of meal size. Am J Physiol Regul Integr Comp Physiol. 2011;301(6):R1692–9.PubMed
149.
Zurück zum Zitat van den Pol AN, Acuna-Goycolea C, Clark KR, Ghosh PK. Physiological properties of hypothalamic MCH neurons identified with selective expression of reporter gene after recombinant virus infection. Neuron. 2004;42(4):635–52.PubMed van den Pol AN, Acuna-Goycolea C, Clark KR, Ghosh PK. Physiological properties of hypothalamic MCH neurons identified with selective expression of reporter gene after recombinant virus infection. Neuron. 2004;42(4):635–52.PubMed
150.
Zurück zum Zitat Bittencourt JC, Presse F, Arias C, Peto C, Vaughan J, Nahon JL, et al. The melanin-concentrating hormone system of the rat brain: an immuno- and hybridization histochemical characterization. J Comp Neurol. 1992;319(2):218–45.PubMed Bittencourt JC, Presse F, Arias C, Peto C, Vaughan J, Nahon JL, et al. The melanin-concentrating hormone system of the rat brain: an immuno- and hybridization histochemical characterization. J Comp Neurol. 1992;319(2):218–45.PubMed
151.
Zurück zum Zitat Qu D, Ludwig DS, Gammeltoft S, Piper M, Pelleymounter MA, Cullen MJ, et al. A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Nature. 1996;380(6571):243–7.PubMed Qu D, Ludwig DS, Gammeltoft S, Piper M, Pelleymounter MA, Cullen MJ, et al. A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Nature. 1996;380(6571):243–7.PubMed
152.
Zurück zum Zitat Ludwig DS, Tritos NA, Mastaitis JW, Kulkarni R, Kokkotou E, Elmquist J, et al. Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J Clin Invest. 2001;107(3):379–86.PubMed Ludwig DS, Tritos NA, Mastaitis JW, Kulkarni R, Kokkotou E, Elmquist J, et al. Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J Clin Invest. 2001;107(3):379–86.PubMed
153.
Zurück zum Zitat Shimada M, Tritos NA, Lowell BB, Flier JS, Maratos-Flier E. Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature. 1998;396(6712):670–4.PubMed Shimada M, Tritos NA, Lowell BB, Flier JS, Maratos-Flier E. Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature. 1998;396(6712):670–4.PubMed
154.
Zurück zum Zitat Mori M, Harada M, Terao Y, Sugo T, Watanabe T, Shimomura Y, et al. Cloning of a novel G protein-coupled receptor, SLT, a subtype of the melanin-concentrating hormone receptor. Biochem Biophys Res Commun. 2001;283(5):1013–8.PubMed Mori M, Harada M, Terao Y, Sugo T, Watanabe T, Shimomura Y, et al. Cloning of a novel G protein-coupled receptor, SLT, a subtype of the melanin-concentrating hormone receptor. Biochem Biophys Res Commun. 2001;283(5):1013–8.PubMed
155.
Zurück zum Zitat Hill J, Duckworth M, Murdock P, Rennie G, Sabido-David C, Ames RS, et al. Molecular cloning and functional characterization of MCH2, a novel human MCH receptor. J Biol Chem. 2001;276(23):20125–9.PubMed Hill J, Duckworth M, Murdock P, Rennie G, Sabido-David C, Ames RS, et al. Molecular cloning and functional characterization of MCH2, a novel human MCH receptor. J Biol Chem. 2001;276(23):20125–9.PubMed
156.
Zurück zum Zitat Sailer AW, Sano H, Zeng Z, McDonald TP, Pan J, Pong SS, et al. Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R. Proc Natl Acad Sci U S A. 2001;98(13):7564–9.PubMed Sailer AW, Sano H, Zeng Z, McDonald TP, Pan J, Pong SS, et al. Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R. Proc Natl Acad Sci U S A. 2001;98(13):7564–9.PubMed
157.
Zurück zum Zitat An S, Cutler G, Zhao JJ, Huang SG, Tian H, Li W, et al. Identification and characterization of a melanin-concentrating hormone receptor. Proc Natl Acad Sci U S A. 2001;98(13):7576–81.PubMed An S, Cutler G, Zhao JJ, Huang SG, Tian H, Li W, et al. Identification and characterization of a melanin-concentrating hormone receptor. Proc Natl Acad Sci U S A. 2001;98(13):7576–81.PubMed
158.
Zurück zum Zitat Wang S, Behan J, O’Neill K, Weig B, Fried S, Laz T, et al. Identification and pharmacological characterization of a novel human melanin-concentrating hormone receptor, mch-r2. J Biol Chem. 2001;276(37):34664–70.PubMed Wang S, Behan J, O’Neill K, Weig B, Fried S, Laz T, et al. Identification and pharmacological characterization of a novel human melanin-concentrating hormone receptor, mch-r2. J Biol Chem. 2001;276(37):34664–70.PubMed
159.
Zurück zum Zitat Marsh DJ, Weingarth DT, Novi DE, Chen HY, Trumbauer ME, Chen AS, et al. Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proc Natl Acad Sci U S A. 2002;99(5):3240–5.PubMed Marsh DJ, Weingarth DT, Novi DE, Chen HY, Trumbauer ME, Chen AS, et al. Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proc Natl Acad Sci U S A. 2002;99(5):3240–5.PubMed
160.
Zurück zum Zitat Szczypka MS, Mandel RJ, Donahue BA, Snyder RO, Leff SE, Palmiter RD. Viral gene delivery selectively restores feeding and prevents lethality of dopamine-deficient mice. Neuron. 1999;22(1):167–78.PubMed Szczypka MS, Mandel RJ, Donahue BA, Snyder RO, Leff SE, Palmiter RD. Viral gene delivery selectively restores feeding and prevents lethality of dopamine-deficient mice. Neuron. 1999;22(1):167–78.PubMed
161.
Zurück zum Zitat Palmiter RD. Is dopamine a physiologically relevant mediator of feeding behavior? Trends in neurosciences. 2007;30(8):375–81.PubMed Palmiter RD. Is dopamine a physiologically relevant mediator of feeding behavior? Trends in neurosciences. 2007;30(8):375–81.PubMed
162.
Zurück zum Zitat Grace AA, Bunney BS. The control of firing pattern in nigral dopamine neurons: burst firing. J Neurosci. 1984;4(11):2877–90.PubMed Grace AA, Bunney BS. The control of firing pattern in nigral dopamine neurons: burst firing. J Neurosci. 1984;4(11):2877–90.PubMed
163.
Zurück zum Zitat Mameli-Engvall M, Evrard A, Pons S, Maskos U, Svensson TH, Changeux JP, et al. Hierarchical control of dopamine neuron-firing patterns by nicotinic receptors. Neuron. 2006;50(6):911–21.PubMed Mameli-Engvall M, Evrard A, Pons S, Maskos U, Svensson TH, Changeux JP, et al. Hierarchical control of dopamine neuron-firing patterns by nicotinic receptors. Neuron. 2006;50(6):911–21.PubMed
164.
Zurück zum Zitat van Zessen R, Phillips JL, Budygin EA, Stuber GD. Activation of VTA GABA neurons disrupts reward consumption. Neuron. 2012;73(6):1184–94.PubMed van Zessen R, Phillips JL, Budygin EA, Stuber GD. Activation of VTA GABA neurons disrupts reward consumption. Neuron. 2012;73(6):1184–94.PubMed
165.
Zurück zum Zitat Noel MB, Wise RA. Ventral tegmental injections of a selective mu or delta opioid enhance feeding in food-deprived rats. Brain Res. 1995;673(2):304–12.PubMed Noel MB, Wise RA. Ventral tegmental injections of a selective mu or delta opioid enhance feeding in food-deprived rats. Brain Res. 1995;673(2):304–12.PubMed
166.
Zurück zum Zitat Avena NM, Rada PV. Cholinergic modulation of food and drug satiety and withdrawal. Physiol Behav. 2012;106(3):332–6.PubMed Avena NM, Rada PV. Cholinergic modulation of food and drug satiety and withdrawal. Physiol Behav. 2012;106(3):332–6.PubMed
167.
Zurück zum Zitat Pecina S. Opioid reward ‘liking’ and ‘wanting’ in the nucleus accumbens. Physiol Behav. 2008;94(5):675–80.PubMed Pecina S. Opioid reward ‘liking’ and ‘wanting’ in the nucleus accumbens. Physiol Behav. 2008;94(5):675–80.PubMed
168.
Zurück zum Zitat Bermudez-Silva FJ, Cardinal P, Cota D. The role of the endocannabinoid system in the neuroendocrine regulation of energy balance. J Psychopharmacol. 2012;26(1):114–24.PubMed Bermudez-Silva FJ, Cardinal P, Cota D. The role of the endocannabinoid system in the neuroendocrine regulation of energy balance. J Psychopharmacol. 2012;26(1):114–24.PubMed
169.
Zurück zum Zitat Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S, Jarai Z, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature. 2001;410(6830):822–5.PubMed Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S, Jarai Z, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature. 2001;410(6830):822–5.PubMed
170.
Zurück zum Zitat Bielajew C, Shizgal P. Evidence implicating descending fibers in self-stimulation of the medial forebrain bundle. J Neurosci. 1986;6(4):919–29.PubMed Bielajew C, Shizgal P. Evidence implicating descending fibers in self-stimulation of the medial forebrain bundle. J Neurosci. 1986;6(4):919–29.PubMed
171.
Zurück zum Zitat Gallistel CR, Shizgal P, Yeomans JS. A portrait of the substrate for self-stimulation. Psychol Rev. 1981;88(3):228–73.PubMed Gallistel CR, Shizgal P, Yeomans JS. A portrait of the substrate for self-stimulation. Psychol Rev. 1981;88(3):228–73.PubMed
172.
Zurück zum Zitat Olds J. Self-stimulation of the brain; its use to study local effects of hunger, sex, and drugs. Science. 1958;127(3294):315–24.PubMed Olds J. Self-stimulation of the brain; its use to study local effects of hunger, sex, and drugs. Science. 1958;127(3294):315–24.PubMed
173.
Zurück zum Zitat Margules DL, Olds J. Identical “feeding” and “rewarding” systems in the lateral hypothalamus of rats. Science. 1962;135(3501):374–5.PubMed Margules DL, Olds J. Identical “feeding” and “rewarding” systems in the lateral hypothalamus of rats. Science. 1962;135(3501):374–5.PubMed
174.
Zurück zum Zitat Harris GC, Wimmer M, Aston-Jones G. A role for lateral hypothalamic orexin neurons in reward seeking. Nature. 2005;437(7058):556–9.PubMed Harris GC, Wimmer M, Aston-Jones G. A role for lateral hypothalamic orexin neurons in reward seeking. Nature. 2005;437(7058):556–9.PubMed
175.
Zurück zum Zitat Mul JD, la Fleur SE, Toonen PW, Afrasiab-Middelman A, Binnekade R, Schetters D, et al. Chronic loss of melanin-concentrating hormone affects motivational aspects of feeding in the rat. PLoS One. 2011;6(5):e19600.PubMed Mul JD, la Fleur SE, Toonen PW, Afrasiab-Middelman A, Binnekade R, Schetters D, et al. Chronic loss of melanin-concentrating hormone affects motivational aspects of feeding in the rat. PLoS One. 2011;6(5):e19600.PubMed
176.
Zurück zum Zitat Zheng H, Patterson LM, Berthoud HR. Orexin signaling in the ventral tegmental area is required for high-fat appetite induced by opioid stimulation of the nucleus accumbens. J Neurosci. 2007;27(41):11075–82.PubMed Zheng H, Patterson LM, Berthoud HR. Orexin signaling in the ventral tegmental area is required for high-fat appetite induced by opioid stimulation of the nucleus accumbens. J Neurosci. 2007;27(41):11075–82.PubMed
177.
Zurück zum Zitat Chung S, Hopf FW, Nagasaki H, Li CY, Belluzzi JD, Bonci A, et al. The melanin-concentrating hormone system modulates cocaine reward. Proc Natl Acad Sci U S A. 2009;106(16):6772–7.PubMed Chung S, Hopf FW, Nagasaki H, Li CY, Belluzzi JD, Bonci A, et al. The melanin-concentrating hormone system modulates cocaine reward. Proc Natl Acad Sci U S A. 2009;106(16):6772–7.PubMed
178.
Zurück zum Zitat Kenny PJ. Reward mechanisms in obesity: new insights and future directions. Neuron. 2011;69(4):664–79.PubMed Kenny PJ. Reward mechanisms in obesity: new insights and future directions. Neuron. 2011;69(4):664–79.PubMed
179.
Zurück zum Zitat Hommel JD, Trinko R, Sears RM, Georgescu D, Liu ZW, Gao XB, et al. Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron. 2006;51(6):801–10.PubMed Hommel JD, Trinko R, Sears RM, Georgescu D, Liu ZW, Gao XB, et al. Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron. 2006;51(6):801–10.PubMed
180.
Zurück zum Zitat Fulton S, Pissios P, Manchon RP, Stiles L, Frank L, Pothos EN, et al. Leptin regulation of the mesoaccumbens dopamine pathway. Neuron. 2006;51(6):811–22.PubMed Fulton S, Pissios P, Manchon RP, Stiles L, Frank L, Pothos EN, et al. Leptin regulation of the mesoaccumbens dopamine pathway. Neuron. 2006;51(6):811–22.PubMed
181.
Zurück zum Zitat Leinninger GM, Jo YH, Leshan RL, Louis GW, Yang H, Barrera JG, et al. Leptin acts via leptin receptor-expressing lateral hypothalamic neurons to modulate the mesolimbic dopamine system and suppress feeding. Cell Metab. 2009;10(2):89–98.PubMed Leinninger GM, Jo YH, Leshan RL, Louis GW, Yang H, Barrera JG, et al. Leptin acts via leptin receptor-expressing lateral hypothalamic neurons to modulate the mesolimbic dopamine system and suppress feeding. Cell Metab. 2009;10(2):89–98.PubMed
182.
Zurück zum Zitat Leinninger GM, Opland DM, Jo YH, Faouzi M, Christensen L, Cappellucci LA, et al. Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance. Cell Metab. 2011;14(3):313–23.PubMed Leinninger GM, Opland DM, Jo YH, Faouzi M, Christensen L, Cappellucci LA, et al. Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance. Cell Metab. 2011;14(3):313–23.PubMed
183.
Zurück zum Zitat Labouebe G, Liu S, Dias C, Zou H, Wong JC, Karunakaran S, et al. Insulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids. Nat Neurosci. 2013;16(3):300–8.PubMed Labouebe G, Liu S, Dias C, Zou H, Wong JC, Karunakaran S, et al. Insulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids. Nat Neurosci. 2013;16(3):300–8.PubMed
184.
Zurück zum Zitat Abizaid A, Liu ZW, Andrews ZB, Shanabrough M, Borok E, Elsworth JD, et al. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. J Clin Invest. 2006;116(12):3229–39.PubMed Abizaid A, Liu ZW, Andrews ZB, Shanabrough M, Borok E, Elsworth JD, et al. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. J Clin Invest. 2006;116(12):3229–39.PubMed
185.
Zurück zum Zitat Malik S, McGlone F, Bedrossian D, Dagher A. Ghrelin modulates brain activity in areas that control appetitive behavior. Cell Metab. 2008;7(5):400–9.PubMed Malik S, McGlone F, Bedrossian D, Dagher A. Ghrelin modulates brain activity in areas that control appetitive behavior. Cell Metab. 2008;7(5):400–9.PubMed
186.
Zurück zum Zitat Lockie SH, Heppner KM, Chaudhary N, Chabenne JR, Morgan DA, Veyrat-Durebex C, et al. Direct control of brown adipose tissue thermogenesis by central nervous system glucagon-like peptide-1 receptor signaling. Diabetes. 2012;61(11):2753–62.PubMed Lockie SH, Heppner KM, Chaudhary N, Chabenne JR, Morgan DA, Veyrat-Durebex C, et al. Direct control of brown adipose tissue thermogenesis by central nervous system glucagon-like peptide-1 receptor signaling. Diabetes. 2012;61(11):2753–62.PubMed
187.
Zurück zum Zitat Whittle AJ, Carobbio S, Martins L, Slawik M, Hondares E, Vazquez MJ, et al. BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell. 2012;149(4):871–85.PubMed Whittle AJ, Carobbio S, Martins L, Slawik M, Hondares E, Vazquez MJ, et al. BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell. 2012;149(4):871–85.PubMed
188.
Zurück zum Zitat Cardinal P, Bellocchio L, Clark S, Cannich A, Klugmann M, Lutz B, et al. Hypothalamic CB1 cannabinoid receptors regulate energy balance in mice. Endocrinology. 2012;153(9):4136–43.PubMed Cardinal P, Bellocchio L, Clark S, Cannich A, Klugmann M, Lutz B, et al. Hypothalamic CB1 cannabinoid receptors regulate energy balance in mice. Endocrinology. 2012;153(9):4136–43.PubMed
189.
Zurück zum Zitat Ueta CB, Fernandes GW, Capelo LP, Fonseca TL, Maculan FD, Gouveia CH, et al. beta(1) Adrenergic receptor is key to cold- and diet-induced thermogenesis in mice. J Endocrinol. 2012;214(3):359–65.PubMed Ueta CB, Fernandes GW, Capelo LP, Fonseca TL, Maculan FD, Gouveia CH, et al. beta(1) Adrenergic receptor is key to cold- and diet-induced thermogenesis in mice. J Endocrinol. 2012;214(3):359–65.PubMed
190.
Zurück zum Zitat Susulic VS, Frederich RC, Lawitts J, Tozzo E, Kahn BB, Harper ME, et al. Targeted disruption of the beta 3-adrenergic receptor gene. J Biol Chem. 1995;270(49):29483–92.PubMed Susulic VS, Frederich RC, Lawitts J, Tozzo E, Kahn BB, Harper ME, et al. Targeted disruption of the beta 3-adrenergic receptor gene. J Biol Chem. 1995;270(49):29483–92.PubMed
191.
Zurück zum Zitat Bachman ES, Dhillon H, Zhang CY, Cinti S, Bianco AC, Kobilka BK, et al. betaAR signaling required for diet-induced thermogenesis and obesity resistance. Science. 2002;297(5582):843–5.PubMed Bachman ES, Dhillon H, Zhang CY, Cinti S, Bianco AC, Kobilka BK, et al. betaAR signaling required for diet-induced thermogenesis and obesity resistance. Science. 2002;297(5582):843–5.PubMed
192.
Zurück zum Zitat Nakamura K, Matsumura K, Hubschle T, Nakamura Y, Hioki H, Fujiyama F, et al. Identification of sympathetic premotor neurons in medullary raphe regions mediating fever and other thermoregulatory functions. J Neurosci. 2004;24(23):5370–80.PubMed Nakamura K, Matsumura K, Hubschle T, Nakamura Y, Hioki H, Fujiyama F, et al. Identification of sympathetic premotor neurons in medullary raphe regions mediating fever and other thermoregulatory functions. J Neurosci. 2004;24(23):5370–80.PubMed
193.
Zurück zum Zitat Kong D, Tong Q, Ye C, Koda S, Fuller PM, Krashes MJ, et al. GABAergic RIP-Cre neurons in the arcuate nucleus selectively regulate energy expenditure. Cell. 2012;151(3):645–57.PubMed Kong D, Tong Q, Ye C, Koda S, Fuller PM, Krashes MJ, et al. GABAergic RIP-Cre neurons in the arcuate nucleus selectively regulate energy expenditure. Cell. 2012;151(3):645–57.PubMed
194.
Zurück zum Zitat Madden CJ, Tupone D, Cano G, Morrison SF. alpha2 Adrenergic receptor-mediated inhibition of thermogenesis. J Neurosci. 2013;33(5):2017–28.PubMed Madden CJ, Tupone D, Cano G, Morrison SF. alpha2 Adrenergic receptor-mediated inhibition of thermogenesis. J Neurosci. 2013;33(5):2017–28.PubMed
195.
Zurück zum Zitat Cao WH, Madden CJ, Morrison SF. Inhibition of brown adipose tissue thermogenesis by neurons in the ventrolateral medulla and in the nucleus tractus solitarius. Am J Physiol Regul Integr Comp Physiol. 2010;299(1):R277–90.PubMed Cao WH, Madden CJ, Morrison SF. Inhibition of brown adipose tissue thermogenesis by neurons in the ventrolateral medulla and in the nucleus tractus solitarius. Am J Physiol Regul Integr Comp Physiol. 2010;299(1):R277–90.PubMed
196.
Zurück zum Zitat Yoshida K, Li X, Cano G, Lazarus M, Saper CB. Parallel preoptic pathways for thermoregulation. J Neurosci. 2009;29(38):11954–64.PubMed Yoshida K, Li X, Cano G, Lazarus M, Saper CB. Parallel preoptic pathways for thermoregulation. J Neurosci. 2009;29(38):11954–64.PubMed
197.
Zurück zum Zitat Dimicco JA, Zaretsky DV. The dorsomedial hypothalamus: a new player in thermoregulation. Am J Physiol Regul Integr Comp Physiol. 2007;292(1):R47–63.PubMed Dimicco JA, Zaretsky DV. The dorsomedial hypothalamus: a new player in thermoregulation. Am J Physiol Regul Integr Comp Physiol. 2007;292(1):R47–63.PubMed
198.
Zurück zum Zitat Chao PT, Yang L, Aja S, Moran TH, Bi S. Knockdown of NPY expression in the dorsomedial hypothalamus promotes development of brown adipocytes and prevents diet-induced obesity. Cell Metab. 2011;13(5):573–83.PubMed Chao PT, Yang L, Aja S, Moran TH, Bi S. Knockdown of NPY expression in the dorsomedial hypothalamus promotes development of brown adipocytes and prevents diet-induced obesity. Cell Metab. 2011;13(5):573–83.PubMed
199.
Zurück zum Zitat Wu J, Cohen P, Spiegelman BM. Adaptive thermogenesis in adipocytes: is beige the new brown? Genes Dev. 2013;27(3):234–50.PubMed Wu J, Cohen P, Spiegelman BM. Adaptive thermogenesis in adipocytes: is beige the new brown? Genes Dev. 2013;27(3):234–50.PubMed
200.
Zurück zum Zitat Sethi J, Sanchez-Alavez M, Tabarean IV. Loss of histaminergic modulation of thermoregulation and energy homeostasis in obese mice. Neuroscience. 2012;217:84–95.PubMed Sethi J, Sanchez-Alavez M, Tabarean IV. Loss of histaminergic modulation of thermoregulation and energy homeostasis in obese mice. Neuroscience. 2012;217:84–95.PubMed
201.
Zurück zum Zitat Morrison SF, Madden CJ, Tupone D. Central control of brown adipose tissue thermogenesis. Frontiers in endocrinology. 2012 Jan 24;3(5). Morrison SF, Madden CJ, Tupone D. Central control of brown adipose tissue thermogenesis. Frontiers in endocrinology. 2012 Jan 24;3(5).
202.
Zurück zum Zitat Enriori PJ, Sinnayah P, Simonds SE, Garcia Rudaz C, Cowley MA. Leptin action in the dorsomedial hypothalamus increases sympathetic tone to brown adipose tissue in spite of systemic leptin resistance. J Neurosci. 2011;31(34):12189–97.PubMed Enriori PJ, Sinnayah P, Simonds SE, Garcia Rudaz C, Cowley MA. Leptin action in the dorsomedial hypothalamus increases sympathetic tone to brown adipose tissue in spite of systemic leptin resistance. J Neurosci. 2011;31(34):12189–97.PubMed
203.
Zurück zum Zitat Rossi J, Balthasar N, Olson D, Scott M, Berglund E, Lee CE, et al. Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis. Cell Metab. 2011;13(2):195–204.PubMed Rossi J, Balthasar N, Olson D, Scott M, Berglund E, Lee CE, et al. Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis. Cell Metab. 2011;13(2):195–204.PubMed
204.
Zurück zum Zitat Shi YC, Lau J, Lin Z, Zhang H, Zhai L, Sperk G, et al. Arcuate NPY Controls Sympathetic Output and BAT Function via a Relay of Tyrosine Hydroxylase Neurons in the PVN. Cell Metab. 2013;17(2):236–48.PubMed Shi YC, Lau J, Lin Z, Zhang H, Zhai L, Sperk G, et al. Arcuate NPY Controls Sympathetic Output and BAT Function via a Relay of Tyrosine Hydroxylase Neurons in the PVN. Cell Metab. 2013;17(2):236–48.PubMed
205.
Zurück zum Zitat Xu Y, Nedungadi TP, Zhu L, Sobhani N, Irani BG, Davis KE, et al. Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell Metab. 2011;14(4):453–65.PubMed Xu Y, Nedungadi TP, Zhu L, Sobhani N, Irani BG, Davis KE, et al. Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell Metab. 2011;14(4):453–65.PubMed
206.
Zurück zum Zitat Lopez M, Varela L, Vazquez MJ, Rodriguez-Cuenca S, Gonzalez CR, Velagapudi VR, et al. Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat Med. 2010;16(9):1001–8.PubMed Lopez M, Varela L, Vazquez MJ, Rodriguez-Cuenca S, Gonzalez CR, Velagapudi VR, et al. Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat Med. 2010;16(9):1001–8.PubMed
207.
Zurück zum Zitat Cao L, Choi EY, Liu X, Martin A, Wang C, Xu X, et al. White to brown fat phenotypic switch induced by genetic and environmental activation of a hypothalamic-adipocyte axis. Cell Metab. 2011;14(3):324–38.PubMed Cao L, Choi EY, Liu X, Martin A, Wang C, Xu X, et al. White to brown fat phenotypic switch induced by genetic and environmental activation of a hypothalamic-adipocyte axis. Cell Metab. 2011;14(3):324–38.PubMed
208.
Zurück zum Zitat Nixon JP, Kotz CM, Novak CM, Billington CJ, Teske JA. Neuropeptides controlling energy balance: orexins and neuromedins. Handbook of Experimental Pharmacology. 2012;209:77–109. Nixon JP, Kotz CM, Novak CM, Billington CJ, Teske JA. Neuropeptides controlling energy balance: orexins and neuromedins. Handbook of Experimental Pharmacology. 2012;209:77–109.
209.
Zurück zum Zitat Tupone D, Madden CJ, Cano G, Morrison SF. An orexinergic projection from perifornical hypothalamus to raphe pallidus increases rat brown adipose tissue thermogenesis. J Neurosci. 2011;31(44):15944–55.PubMed Tupone D, Madden CJ, Cano G, Morrison SF. An orexinergic projection from perifornical hypothalamus to raphe pallidus increases rat brown adipose tissue thermogenesis. J Neurosci. 2011;31(44):15944–55.PubMed
210.
Zurück zum Zitat Perez-Leighton CE, Boland K, Teske JA, Billington C, Kotz CM. Behavioral responses to orexin, orexin receptor gene expression, and spontaneous physical activity contribute to individual sensitivity to obesity. Am J Physiol Endocrinol Metab. 2012;303(7):E865–74.PubMed Perez-Leighton CE, Boland K, Teske JA, Billington C, Kotz CM. Behavioral responses to orexin, orexin receptor gene expression, and spontaneous physical activity contribute to individual sensitivity to obesity. Am J Physiol Endocrinol Metab. 2012;303(7):E865–74.PubMed
211.
Zurück zum Zitat Song CK, Vaughan CH, Keen-Rhinehart E, Harris RB, Richard D, Bartness TJ. Melanocortin-4 receptor mRNA expressed in sympathetic outflow neurons to brown adipose tissue: neuroanatomical and functional evidence. Am J Physiol Regul Integr Comp Physiol. 2008;295(2):R417–28.PubMed Song CK, Vaughan CH, Keen-Rhinehart E, Harris RB, Richard D, Bartness TJ. Melanocortin-4 receptor mRNA expressed in sympathetic outflow neurons to brown adipose tissue: neuroanatomical and functional evidence. Am J Physiol Regul Integr Comp Physiol. 2008;295(2):R417–28.PubMed
212.
Zurück zum Zitat Hollenberg AN. The role of the thyrotropin-releasing hormone (TRH) neuron as a metabolic sensor. Thyroid. 2008;18(2):131–9.PubMed Hollenberg AN. The role of the thyrotropin-releasing hormone (TRH) neuron as a metabolic sensor. Thyroid. 2008;18(2):131–9.PubMed
213.
Zurück zum Zitat Nieuwenhuizen AG, Rutters F. The hypothalamic-pituitary-adrenal-axis in the regulation of energy balance. Physiol Behav. 2008;94(2):169–77.PubMed Nieuwenhuizen AG, Rutters F. The hypothalamic-pituitary-adrenal-axis in the regulation of energy balance. Physiol Behav. 2008;94(2):169–77.PubMed
214.
Zurück zum Zitat Valassi E, Scacchi M, Cavagnini F. Neuroendocrine control of food intake. Nutr Metab Cardiovasc Dis. 2008;18(2):158–68.PubMed Valassi E, Scacchi M, Cavagnini F. Neuroendocrine control of food intake. Nutr Metab Cardiovasc Dis. 2008;18(2):158–68.PubMed
215.
Zurück zum Zitat Gonzalez JA, Horjales-Araujo E, Fugger L, Broberger C, Burdakov D. Stimulation of orexin/hypocretin neurones by thyrotropin-releasing hormone. J Physiol. 2009;587(Pt 6):1179–86.PubMed Gonzalez JA, Horjales-Araujo E, Fugger L, Broberger C, Burdakov D. Stimulation of orexin/hypocretin neurones by thyrotropin-releasing hormone. J Physiol. 2009;587(Pt 6):1179–86.PubMed
216.
Zurück zum Zitat Hara J, Gerashchenko D, Wisor JP, Sakurai T, Xie X, Kilduff TS. Thyrotropin-releasing hormone increases behavioral arousal through modulation of hypocretin/orexin neurons. J Neurosci. 2009;29(12):3705–14.PubMed Hara J, Gerashchenko D, Wisor JP, Sakurai T, Xie X, Kilduff TS. Thyrotropin-releasing hormone increases behavioral arousal through modulation of hypocretin/orexin neurons. J Neurosci. 2009;29(12):3705–14.PubMed
217.
Zurück zum Zitat Cerri M, Morrison SF. Corticotropin releasing factor increases in brown adipose tissue thermogenesis and heart rate through dorsomedial hypothalamus and medullary raphe pallidus. Neuroscience. 2006;140(2):711–21.PubMed Cerri M, Morrison SF. Corticotropin releasing factor increases in brown adipose tissue thermogenesis and heart rate through dorsomedial hypothalamus and medullary raphe pallidus. Neuroscience. 2006;140(2):711–21.PubMed
218.
Zurück zum Zitat Madden CJ, Morrison SF. Neurons in the paraventricular nucleus of the hypothalamus inhibit sympathetic outflow to brown adipose tissue. Am J Physiol Regul Integr Comp Physiol. 2009;296(3):R831–43.PubMed Madden CJ, Morrison SF. Neurons in the paraventricular nucleus of the hypothalamus inhibit sympathetic outflow to brown adipose tissue. Am J Physiol Regul Integr Comp Physiol. 2009;296(3):R831–43.PubMed
219.
Zurück zum Zitat Sawchenko PE, Swanson LW, Grzanna R, Howe PR, Bloom SR, Polak JM. Colocalization of neuropeptide Y immunoreactivity in brainstem catecholaminergic neurons that project to the paraventricular nucleus of the hypothalamus. J Comp Neurol. 1985;241(2):138–53.PubMed Sawchenko PE, Swanson LW, Grzanna R, Howe PR, Bloom SR, Polak JM. Colocalization of neuropeptide Y immunoreactivity in brainstem catecholaminergic neurons that project to the paraventricular nucleus of the hypothalamus. J Comp Neurol. 1985;241(2):138–53.PubMed
220.
Zurück zum Zitat Lechan RM, Fekete C. The TRH neuron: a hypothalamic integrator of energy metabolism. Progress in brain research. 2006;153:209–35.PubMed Lechan RM, Fekete C. The TRH neuron: a hypothalamic integrator of energy metabolism. Progress in brain research. 2006;153:209–35.PubMed
221.
Zurück zum Zitat Scott R, Tan T, Bloom S. Gut hormones and obesity: physiology and therapies. Vitamins and hormones. 2013;91:143–94.PubMed Scott R, Tan T, Bloom S. Gut hormones and obesity: physiology and therapies. Vitamins and hormones. 2013;91:143–94.PubMed
223.
Zurück zum Zitat Tsukita S, Yamada T, Uno K, Takahashi K, Kaneko K, Ishigaki Y, et al. Hepatic glucokinase modulates obesity predisposition by regulating BAT thermogenesis via neural signals. Cell Metab. 2012;16(6):825–32.PubMed Tsukita S, Yamada T, Uno K, Takahashi K, Kaneko K, Ishigaki Y, et al. Hepatic glucokinase modulates obesity predisposition by regulating BAT thermogenesis via neural signals. Cell Metab. 2012;16(6):825–32.PubMed
224.
Zurück zum Zitat Blouet C, Schwartz GJ. Duodenal lipid sensing activates vagal afferents to regulate non-shivering brown fat thermogenesis in rats. PLoS One. 2012;7(12):e51898.PubMed Blouet C, Schwartz GJ. Duodenal lipid sensing activates vagal afferents to regulate non-shivering brown fat thermogenesis in rats. PLoS One. 2012;7(12):e51898.PubMed
225.
Zurück zum Zitat Harris M, Aschkenasi C, Elias CF, Chandrankunnel A, Nillni EA, Bjoorbaek C, et al. Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling. J Clin Invest. 2001;107(1):111–20.PubMed Harris M, Aschkenasi C, Elias CF, Chandrankunnel A, Nillni EA, Bjoorbaek C, et al. Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling. J Clin Invest. 2001;107(1):111–20.PubMed
226.
Zurück zum Zitat Huo L, Munzberg H, Nillni EA, Bjorbaek C. Role of signal transducer and activator of transcription 3 in regulation of hypothalamic trh gene expression by leptin. Endocrinology. 2004;145(5):2516–23.PubMed Huo L, Munzberg H, Nillni EA, Bjorbaek C. Role of signal transducer and activator of transcription 3 in regulation of hypothalamic trh gene expression by leptin. Endocrinology. 2004;145(5):2516–23.PubMed
227.
Zurück zum Zitat Guo F, Bakal K, Minokoshi Y, Hollenberg AN. Leptin signaling targets the thyrotropin-releasing hormone gene promoter in vivo. Endocrinology. 2004;145(5):2221–7.PubMed Guo F, Bakal K, Minokoshi Y, Hollenberg AN. Leptin signaling targets the thyrotropin-releasing hormone gene promoter in vivo. Endocrinology. 2004;145(5):2221–7.PubMed
228.
Zurück zum Zitat Zhang Y, Kerman IA, Laque A, Nguyen P, Faouzi M, Louis GW, et al. Leptin-receptor-expressing neurons in the dorsomedial hypothalamus and median preoptic area regulate sympathetic brown adipose tissue circuits. J Neurosci. 2011;31(5):1873–84.PubMed Zhang Y, Kerman IA, Laque A, Nguyen P, Faouzi M, Louis GW, et al. Leptin-receptor-expressing neurons in the dorsomedial hypothalamus and median preoptic area regulate sympathetic brown adipose tissue circuits. J Neurosci. 2011;31(5):1873–84.PubMed
229.
Zurück zum Zitat Holsen LM, Savage CR, Martin LE, Bruce AS, Lepping RJ, Ko E, et al. Importance of reward and prefrontal circuitry in hunger and satiety: Prader-Willi syndrome vs simple obesity. Int J Obes (Lond). 2012;36(5):638–47. Holsen LM, Savage CR, Martin LE, Bruce AS, Lepping RJ, Ko E, et al. Importance of reward and prefrontal circuitry in hunger and satiety: Prader-Willi syndrome vs simple obesity. Int J Obes (Lond). 2012;36(5):638–47.
230.
Zurück zum Zitat Williams DL, Baskin DG, Schwartz MW. Hindbrain leptin receptor stimulation enhances the anorexic response to cholecystokinin. Am J Physiol Regul Integr Comp Physiol. 2009;297(5):R1238–46.PubMed Williams DL, Baskin DG, Schwartz MW. Hindbrain leptin receptor stimulation enhances the anorexic response to cholecystokinin. Am J Physiol Regul Integr Comp Physiol. 2009;297(5):R1238–46.PubMed
231.
Zurück zum Zitat Hayes MR, Skibicka KP, Leichner TM, Guarnieri DJ, DiLeone RJ, Bence KK, et al. Endogenous leptin signaling in the caudal nucleus tractus solitarius and area postrema is required for energy balance regulation. Cell Metab. 2010;11(1):77–83.PubMed Hayes MR, Skibicka KP, Leichner TM, Guarnieri DJ, DiLeone RJ, Bence KK, et al. Endogenous leptin signaling in the caudal nucleus tractus solitarius and area postrema is required for energy balance regulation. Cell Metab. 2010;11(1):77–83.PubMed
232.
Zurück zum Zitat Ren D, Li M, Duan C, Rui L. Identification of SH2-B as a key regulator of leptin sensitivity, energy balance, and body weight in mice. Cell Metabolism. 2005;2(2):95–104.PubMed Ren D, Li M, Duan C, Rui L. Identification of SH2-B as a key regulator of leptin sensitivity, energy balance, and body weight in mice. Cell Metabolism. 2005;2(2):95–104.PubMed
233.
Zurück zum Zitat Ren D, Zhou Y, Morris D, Li M, Li Z, Rui L. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. J Clin Invest. 2007;117(2):397–406.PubMed Ren D, Zhou Y, Morris D, Li M, Li Z, Rui L. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. J Clin Invest. 2007;117(2):397–406.PubMed
234.
Zurück zum Zitat Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet. 2009;41(1):18–24.PubMed Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet. 2009;41(1):18–24.PubMed
235.
Zurück zum Zitat Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet. 2009;41(1):25–34.PubMed Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet. 2009;41(1):25–34.PubMed
236.
Zurück zum Zitat Jamshidi Y, Snieder H, Ge D, Spector TD, O’Dell SD. The SH2B gene is associated with serum leptin and body fat in normal female twins. Obesity (Silver Spring). 2007;15(1):5–9.PubMed Jamshidi Y, Snieder H, Ge D, Spector TD, O’Dell SD. The SH2B gene is associated with serum leptin and body fat in normal female twins. Obesity (Silver Spring). 2007;15(1):5–9.PubMed
237.
Zurück zum Zitat Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010;42(11):937–48.PubMed Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010;42(11):937–48.PubMed
238.
Zurück zum Zitat Shi J, Long J, Gao YT, Lu W, Cai Q, Wen W, et al. Evaluation of genetic susceptibility loci for obesity in Chinese women. Am J Epidemiol. 2010;172(3):244–54.PubMed Shi J, Long J, Gao YT, Lu W, Cai Q, Wen W, et al. Evaluation of genetic susceptibility loci for obesity in Chinese women. Am J Epidemiol. 2010;172(3):244–54.PubMed
239.
Zurück zum Zitat Ng MC, Tam CH, So WY, Ho JS, Chan AW, Lee HM, et al. Implication of genetic variants near NEGR1, SEC16B, TMEM18, ETV5/DGKG, GNPDA2, LIN7C/BDNF, MTCH2, BCDIN3D/FAIM2, SH2B1, FTO, MC4R, and KCTD15 with obesity and type 2 diabetes in 7705 Chinese. J Clin Endocrinol Metab. 2010;95(5):2418–25.PubMed Ng MC, Tam CH, So WY, Ho JS, Chan AW, Lee HM, et al. Implication of genetic variants near NEGR1, SEC16B, TMEM18, ETV5/DGKG, GNPDA2, LIN7C/BDNF, MTCH2, BCDIN3D/FAIM2, SH2B1, FTO, MC4R, and KCTD15 with obesity and type 2 diabetes in 7705 Chinese. J Clin Endocrinol Metab. 2010;95(5):2418–25.PubMed
240.
Zurück zum Zitat Paternoster L, Evans DM, Nohr EA, Holst C, Gaborieau V, Brennan P, et al. Genome-wide population-based association study of extremely overweight young adults–the GOYA study. PLoS One. 2011;6(9):e24303.PubMed Paternoster L, Evans DM, Nohr EA, Holst C, Gaborieau V, Brennan P, et al. Genome-wide population-based association study of extremely overweight young adults–the GOYA study. PLoS One. 2011;6(9):e24303.PubMed
241.
Zurück zum Zitat Sandholt CH, Vestmar MA, Bille DS, Borglykke A, Almind K, Hansen L, et al. Studies of metabolic phenotypic correlates of 15 obesity associated gene variants. PLoS One. 2011;6(9):e23531.PubMed Sandholt CH, Vestmar MA, Bille DS, Borglykke A, Almind K, Hansen L, et al. Studies of metabolic phenotypic correlates of 15 obesity associated gene variants. PLoS One. 2011;6(9):e23531.PubMed
242.
Zurück zum Zitat Haupt A, Thamer C, Heni M, Machicao F, Machann J, Schick F, et al. Novel obesity risk loci do not determine distribution of body fat depots: a whole-body MRI/MRS study. Obesity (Silver Spring). 2010;18(6):1212–7.PubMed Haupt A, Thamer C, Heni M, Machicao F, Machann J, Schick F, et al. Novel obesity risk loci do not determine distribution of body fat depots: a whole-body MRI/MRS study. Obesity (Silver Spring). 2010;18(6):1212–7.PubMed
243.
Zurück zum Zitat Renstrom F, Payne F, Nordstrom A, Brito EC, Rolandsson O, Hallmans G, et al. Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden. Hum Mol Genet. 2009;18(8):1489–96.PubMed Renstrom F, Payne F, Nordstrom A, Brito EC, Rolandsson O, Hallmans G, et al. Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden. Hum Mol Genet. 2009;18(8):1489–96.PubMed
244.
Zurück zum Zitat Holzapfel C, Grallert H, Huth C, Wahl S, Fischer B, Doring A, et al. Genes and lifestyle factors in obesity: results from 12,462 subjects from MONICA/KORA. Int J Obes (Lond). 2010;34(10):1538–45. Holzapfel C, Grallert H, Huth C, Wahl S, Fischer B, Doring A, et al. Genes and lifestyle factors in obesity: results from 12,462 subjects from MONICA/KORA. Int J Obes (Lond). 2010;34(10):1538–45.
245.
Zurück zum Zitat Prudente S, Morini E, Larmon J, Andreozzi F, Di Pietro N, Nigro A, et al. The SH2B1 obesity locus is associated with myocardial infarction in diabetic patients and with NO synthase activity in endothelial cells. Atherosclerosis. 2011;219(2):667–72.PubMed Prudente S, Morini E, Larmon J, Andreozzi F, Di Pietro N, Nigro A, et al. The SH2B1 obesity locus is associated with myocardial infarction in diabetic patients and with NO synthase activity in endothelial cells. Atherosclerosis. 2011;219(2):667–72.PubMed
246.
Zurück zum Zitat Hotta K, Kitamoto T, Kitamoto A, Mizusawa S, Matsuo T, Nakata Y, et al. Computed tomography analysis of the association between the SH2B1 rs7498665 single-nucleotide polymorphism and visceral fat area. J Hum Genet. 2011;56(10):716–9.PubMed Hotta K, Kitamoto T, Kitamoto A, Mizusawa S, Matsuo T, Nakata Y, et al. Computed tomography analysis of the association between the SH2B1 rs7498665 single-nucleotide polymorphism and visceral fat area. J Hum Genet. 2011;56(10):716–9.PubMed
247.
Zurück zum Zitat Takeuchi F, Yamamoto K, Katsuya T, Nabika T, Sugiyama T, Fujioka A, et al. Association of genetic variants for susceptibility to obesity with type 2 diabetes in Japanese individuals. Diabetologia. 2011;54(6):1350–9.PubMed Takeuchi F, Yamamoto K, Katsuya T, Nabika T, Sugiyama T, Fujioka A, et al. Association of genetic variants for susceptibility to obesity with type 2 diabetes in Japanese individuals. Diabetologia. 2011;54(6):1350–9.PubMed
248.
Zurück zum Zitat Bauer F, Elbers CC, Adan RA, Loos RJ, Onland-Moret NC, Grobbee DE, et al. Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference. Am J Clin Nutr. 2009;90(4):951–9.PubMed Bauer F, Elbers CC, Adan RA, Loos RJ, Onland-Moret NC, Grobbee DE, et al. Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference. Am J Clin Nutr. 2009;90(4):951–9.PubMed
249.
Zurück zum Zitat Orkunoglu-Suer FE, Harmon BT, Gordish-Dressman H, Clarkson PM, Thompson PD, Angelopoulos TJ, et al. MC4R variant is associated with BMI but not response to resistance training in young females. Obesity (Silver Spring). 2011;19(3):662–6.PubMed Orkunoglu-Suer FE, Harmon BT, Gordish-Dressman H, Clarkson PM, Thompson PD, Angelopoulos TJ, et al. MC4R variant is associated with BMI but not response to resistance training in young females. Obesity (Silver Spring). 2011;19(3):662–6.PubMed
250.
Zurück zum Zitat Hester JM, Wing MR, Li J, Palmer ND, Xu J, Hicks PJ, et al. Implication of European-derived adiposity loci in African Americans. Int J Obes (Lond). 2012;36(3):465–73. Hester JM, Wing MR, Li J, Palmer ND, Xu J, Hicks PJ, et al. Implication of European-derived adiposity loci in African Americans. Int J Obes (Lond). 2012;36(3):465–73.
251.
Zurück zum Zitat Bochukova EG, Huang N, Keogh J, Henning E, Purmann C, Blaszczyk K, et al. Large, rare chromosomal deletions associated with severe early-onset obesity. Nature. 2010;463(7281):666–70.PubMed Bochukova EG, Huang N, Keogh J, Henning E, Purmann C, Blaszczyk K, et al. Large, rare chromosomal deletions associated with severe early-onset obesity. Nature. 2010;463(7281):666–70.PubMed
252.
Zurück zum Zitat Doche ME, Bochukova EG, Su HW, Pearce LR, Keogh JM, Henning E, et al. Human SH2B1 mutations are associated with maladaptive behaviors and obesity. J Clin Invest. 2012;122(12):4732–6.PubMed Doche ME, Bochukova EG, Su HW, Pearce LR, Keogh JM, Henning E, et al. Human SH2B1 mutations are associated with maladaptive behaviors and obesity. J Clin Invest. 2012;122(12):4732–6.PubMed
253.
Zurück zum Zitat Duan C, Li M, Rui L. SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin. J Biol Chem. 2004;279(42):43684–91.PubMed Duan C, Li M, Rui L. SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin. J Biol Chem. 2004;279(42):43684–91.PubMed
254.
Zurück zum Zitat Li Z, Zhou Y, Carter-Su C, Myers Jr MG, Rui L. SH2B1 Enhances Leptin Signaling by Both Janus Kinase 2 Tyr813 Phosphorylation-Dependent and -Independent Mechanisms. Mol Endocrinol. 2007;21(9):2270–81.PubMed Li Z, Zhou Y, Carter-Su C, Myers Jr MG, Rui L. SH2B1 Enhances Leptin Signaling by Both Janus Kinase 2 Tyr813 Phosphorylation-Dependent and -Independent Mechanisms. Mol Endocrinol. 2007;21(9):2270–81.PubMed
255.
Zurück zum Zitat Huang H, Kong D, Byun KH, Ye C, Koda S, Lee DH, et al. Rho-kinase regulates energy balance by targeting hypothalamic leptin receptor signaling. Nat Neurosci. 2012;15(10):1391–8.PubMed Huang H, Kong D, Byun KH, Ye C, Koda S, Lee DH, et al. Rho-kinase regulates energy balance by targeting hypothalamic leptin receptor signaling. Nat Neurosci. 2012;15(10):1391–8.PubMed
256.
Zurück zum Zitat Liu Q, Zhang J, Zerbinatti C, Zhan Y, Kolber BJ, Herz J, et al. Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system. PLoS Biol. 2011;9(1):e1000575.PubMed Liu Q, Zhang J, Zerbinatti C, Zhan Y, Kolber BJ, Herz J, et al. Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system. PLoS Biol. 2011;9(1):e1000575.PubMed
257.
Zurück zum Zitat Cone RD. Studies on the physiological functions of the melanocortin system. Endocr Rev. 2006;27(7):736–49.PubMed Cone RD. Studies on the physiological functions of the melanocortin system. Endocr Rev. 2006;27(7):736–49.PubMed
258.
Zurück zum Zitat Mountjoy KG, Mortrud MT, Low MJ, Simerly RB, Cone RD. Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol Endocrinol. 1994;8(10):1298–308.PubMed Mountjoy KG, Mortrud MT, Low MJ, Simerly RB, Cone RD. Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol Endocrinol. 1994;8(10):1298–308.PubMed
259.
Zurück zum Zitat Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. 1998;19(2):155–7.PubMed Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. 1998;19(2):155–7.PubMed
260.
Zurück zum Zitat Gao S, Kinzig KP, Aja S, Scott KA, Keung W, Kelly S, et al. Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intake. Proc Natl Acad Sci U S A. 2007;104(44):17358–63.PubMed Gao S, Kinzig KP, Aja S, Scott KA, Keung W, Kelly S, et al. Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intake. Proc Natl Acad Sci U S A. 2007;104(44):17358–63.PubMed
261.
Zurück zum Zitat Havrankova J, Roth J, Brownstein M. Insulin receptors are widely distributed in the central nervous system of the rat. Nature. 1978;272(5656):827–9.PubMed Havrankova J, Roth J, Brownstein M. Insulin receptors are widely distributed in the central nervous system of the rat. Nature. 1978;272(5656):827–9.PubMed
262.
Zurück zum Zitat Spanswick D, Smith MA, Mirshamsi S, Routh VH, Ashford ML. Insulin activates ATP-sensitive K + channels in hypothalamic neurons of lean, but not obese rats. Nat Neurosci. 2000;3(8):757–8.PubMed Spanswick D, Smith MA, Mirshamsi S, Routh VH, Ashford ML. Insulin activates ATP-sensitive K + channels in hypothalamic neurons of lean, but not obese rats. Nat Neurosci. 2000;3(8):757–8.PubMed
263.
Zurück zum Zitat Woods SC, Lotter EC, McKay LD, Porte Jr D. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature. 1979;282(5738):503–5.PubMed Woods SC, Lotter EC, McKay LD, Porte Jr D. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature. 1979;282(5738):503–5.PubMed
264.
Zurück zum Zitat Sipols AJ, Baskin DG, Schwartz MW. Effect of intracerebroventricular insulin infusion on diabetic hyperphagia and hypothalamic neuropeptide gene expression. Diabetes. 1995;44(2):147–51.PubMed Sipols AJ, Baskin DG, Schwartz MW. Effect of intracerebroventricular insulin infusion on diabetic hyperphagia and hypothalamic neuropeptide gene expression. Diabetes. 1995;44(2):147–51.PubMed
265.
Zurück zum Zitat Schwartz MW, Sipols AJ, Marks JL, Sanacora G, White JD, Scheurink A, et al. Inhibition of hypothalamic neuropeptide Y gene expression by insulin. Endocrinology. 1992;130(6):3608–16.PubMed Schwartz MW, Sipols AJ, Marks JL, Sanacora G, White JD, Scheurink A, et al. Inhibition of hypothalamic neuropeptide Y gene expression by insulin. Endocrinology. 1992;130(6):3608–16.PubMed
266.
Zurück zum Zitat Bruning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, et al. Role of brain insulin receptor in control of body weight and reproduction. Science. 2000;289(5487):2122–5.PubMed Bruning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, et al. Role of brain insulin receptor in control of body weight and reproduction. Science. 2000;289(5487):2122–5.PubMed
267.
Zurück zum Zitat Obici S, Feng Z, Karkanias G, Baskin DG, Rossetti L. Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Nat Neurosci. 2002;5(6):566–72. Obici S, Feng Z, Karkanias G, Baskin DG, Rossetti L. Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Nat Neurosci. 2002;5(6):566–72.
268.
Zurück zum Zitat Begg DP, Mul JD, Liu M, Reedy BM, D’Alessio DA, Seeley RJ, et al. Reversal of diet-induced obesity increases insulin transport into cerebrospinal fluid and restores sensitivity to the anorexic action of central insulin in male rats. Endocrinology. 2013;154(3):1047–54.PubMed Begg DP, Mul JD, Liu M, Reedy BM, D’Alessio DA, Seeley RJ, et al. Reversal of diet-induced obesity increases insulin transport into cerebrospinal fluid and restores sensitivity to the anorexic action of central insulin in male rats. Endocrinology. 2013;154(3):1047–54.PubMed
269.
Zurück zum Zitat Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860–7.PubMed Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860–7.PubMed
270.
Zurück zum Zitat Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, et al. Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest. 2012;122(1):153–62.PubMed Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, et al. Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest. 2012;122(1):153–62.PubMed
271.
Zurück zum Zitat Milanski M, Degasperi G, Coope A, Morari J, Denis R, Cintra DE, et al. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. J Neurosci. 2009;29(2):359–70.PubMed Milanski M, Degasperi G, Coope A, Morari J, Denis R, Cintra DE, et al. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. J Neurosci. 2009;29(2):359–70.PubMed
272.
Zurück zum Zitat Milanski M, Arruda AP, Coope A, Ignacio-Souza LM, Nunez CE, Roman EA, et al. Inhibition of hypothalamic inflammation reverses diet-induced insulin resistance in the liver. Diabetes. 2012;61(6):1455–62.PubMed Milanski M, Arruda AP, Coope A, Ignacio-Souza LM, Nunez CE, Roman EA, et al. Inhibition of hypothalamic inflammation reverses diet-induced insulin resistance in the liver. Diabetes. 2012;61(6):1455–62.PubMed
273.
Zurück zum Zitat Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D. Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell. 2008;135(1):61–73.PubMed Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D. Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell. 2008;135(1):61–73.PubMed
274.
Zurück zum Zitat Li J, Tang Y, Cai D. IKKbeta/NF-kappaB disrupts adult hypothalamic neural stem cells to mediate a neurodegenerative mechanism of dietary obesity and pre-diabetes. Nat Cell Biol. 2012;14(10):999–1012.PubMed Li J, Tang Y, Cai D. IKKbeta/NF-kappaB disrupts adult hypothalamic neural stem cells to mediate a neurodegenerative mechanism of dietary obesity and pre-diabetes. Nat Cell Biol. 2012;14(10):999–1012.PubMed
275.
Zurück zum Zitat Ozcan L, Ergin AS, Lu A, Chung J, Sarkar S, Nie D, et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 2009;9(1):35–51.PubMed Ozcan L, Ergin AS, Lu A, Chung J, Sarkar S, Nie D, et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 2009;9(1):35–51.PubMed
276.
Zurück zum Zitat Zhang H, Zhang G, Gonzalez FJ, Park SM, Cai D. Hypoxia-inducible factor directs POMC gene to mediate hypothalamic glucose sensing and energy balance regulation. PLoS Biol. 2011;9(7):e1001112.PubMed Zhang H, Zhang G, Gonzalez FJ, Park SM, Cai D. Hypoxia-inducible factor directs POMC gene to mediate hypothalamic glucose sensing and energy balance regulation. PLoS Biol. 2011;9(7):e1001112.PubMed
277.
Zurück zum Zitat McNay DE, Briancon N, Kokoeva MV, Maratos-Flier E, Flier JS. Remodeling of the arcuate nucleus energy-balance circuit is inhibited in obese mice. J Clin Invest. 2012;122(1):142–52.PubMed McNay DE, Briancon N, Kokoeva MV, Maratos-Flier E, Flier JS. Remodeling of the arcuate nucleus energy-balance circuit is inhibited in obese mice. J Clin Invest. 2012;122(1):142–52.PubMed
278.
Zurück zum Zitat Horvath TL, Sarman B, Garcia-Caceres C, Enriori PJ, Sotonyi P, Shanabrough M, et al. Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proc Natl Acad Sci U S A. 2010;107(33):14875–80.PubMed Horvath TL, Sarman B, Garcia-Caceres C, Enriori PJ, Sotonyi P, Shanabrough M, et al. Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proc Natl Acad Sci U S A. 2010;107(33):14875–80.PubMed
279.
Zurück zum Zitat Pierce AA, Xu AW. De novo neurogenesis in adult hypothalamus as a compensatory mechanism to regulate energy balance. J Neurosci. 2010;30(2):723–30.PubMed Pierce AA, Xu AW. De novo neurogenesis in adult hypothalamus as a compensatory mechanism to regulate energy balance. J Neurosci. 2010;30(2):723–30.PubMed
280.
Zurück zum Zitat Gage FH. Mammalian neural stem cells. Science. 2000;287(5457):1433–8.PubMed Gage FH. Mammalian neural stem cells. Science. 2000;287(5457):1433–8.PubMed
281.
Zurück zum Zitat Lee DA, Bedont JL, Pak T, Wang H, Song J, Miranda-Angulo A, et al. Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche. Nat Neurosci. 2012;15(5):700–2.PubMed Lee DA, Bedont JL, Pak T, Wang H, Song J, Miranda-Angulo A, et al. Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche. Nat Neurosci. 2012;15(5):700–2.PubMed
282.
Zurück zum Zitat Haan N, Goodman T, Najdi-Samiei A, Stratford CM, Rice R, El Agha E, et al. Fgf10-expressing tanycytes add new neurons to the appetite/energy-balance regulating centers of the postnatal and adult hypothalamus. J Neurosci. 2013;33(14):6170–80.PubMed Haan N, Goodman T, Najdi-Samiei A, Stratford CM, Rice R, El Agha E, et al. Fgf10-expressing tanycytes add new neurons to the appetite/energy-balance regulating centers of the postnatal and adult hypothalamus. J Neurosci. 2013;33(14):6170–80.PubMed
283.
Zurück zum Zitat Kokoeva MV, Yin H, Flier JS. Neurogenesis in the hypothalamus of adult mice: potential role in energy balance. Science. 2005;310(5748):679–83.PubMed Kokoeva MV, Yin H, Flier JS. Neurogenesis in the hypothalamus of adult mice: potential role in energy balance. Science. 2005;310(5748):679–83.PubMed
284.
Zurück zum Zitat Kasischke KA, Vishwasrao HD, Fisher PJ, Zipfel WR, Webb WW. Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science. 2004;305(5680):99–103.PubMed Kasischke KA, Vishwasrao HD, Fisher PJ, Zipfel WR, Webb WW. Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science. 2004;305(5680):99–103.PubMed
285.
Zurück zum Zitat Fuente-Martin E, Garcia-Caceres C, Granado M, de Ceballos ML, Sanchez-Garrido MA, Sarman B, et al. Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes. J Clin Invest. 2012;122(11):3900–13.PubMed Fuente-Martin E, Garcia-Caceres C, Granado M, de Ceballos ML, Sanchez-Garrido MA, Sarman B, et al. Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes. J Clin Invest. 2012;122(11):3900–13.PubMed
286.
Zurück zum Zitat Buckman LB, Thompson MM, Moreno HN, Ellacott KL. Regional astrogliosis in the mouse hypothalamus in response to obesity. J Comp Neurol. 2013;521(6):1322–33. Buckman LB, Thompson MM, Moreno HN, Ellacott KL. Regional astrogliosis in the mouse hypothalamus in response to obesity. J Comp Neurol. 2013;521(6):1322–33.
287.
Zurück zum Zitat Lanfray D, Arthaud S, Ouellet J, Compere V, Do Rego JL, Leprince J, et al. Gliotransmission and brain glucose sensing: critical role of endozepines. Diabetes. 2013;62(3):801–10.PubMed Lanfray D, Arthaud S, Ouellet J, Compere V, Do Rego JL, Leprince J, et al. Gliotransmission and brain glucose sensing: critical role of endozepines. Diabetes. 2013;62(3):801–10.PubMed
288.
Zurück zum Zitat Langlet F, Levin BE, Luquet S, Mazzone M, Messina A, Dunn-Meynell AA, et al. Tanycytic VEGF-A Boosts Blood-Hypothalamus Barrier Plasticity and Access of Metabolic Signals to the Arcuate Nucleus in Response to Fasting. Cell Metab. 2013;17(4):607–17.PubMed Langlet F, Levin BE, Luquet S, Mazzone M, Messina A, Dunn-Meynell AA, et al. Tanycytic VEGF-A Boosts Blood-Hypothalamus Barrier Plasticity and Access of Metabolic Signals to the Arcuate Nucleus in Response to Fasting. Cell Metab. 2013;17(4):607–17.PubMed
Metadaten
Titel
Brain regulation of energy balance and body weight
verfasst von
Liangyou Rui
Publikationsdatum
01.12.2013
Verlag
Springer US
Erschienen in
Reviews in Endocrine and Metabolic Disorders / Ausgabe 4/2013
Print ISSN: 1389-9155
Elektronische ISSN: 1573-2606
DOI
https://doi.org/10.1007/s11154-013-9261-9

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