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Erschienen in: Diabetologia 2/2017

16.12.2016 | Review

Glia: silent partners in energy homeostasis and obesity pathogenesis

verfasst von: John D. Douglass, Mauricio D. Dorfman, Joshua P. Thaler

Erschienen in: Diabetologia | Ausgabe 2/2017

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Abstract

Body weight stability requires homeostatic regulation to balance energy intake and energy expenditure. Research on this system and how it is affected by obesity has largely focused on the role of hypothalamic neurons as integrators of information about long-term fuel storage, short-term nutrient availability and metabolic demand. Recent studies have uncovered glial cells as additional contributors to energy balance regulation and obesity pathogenesis. Beginning with early work on leptin signalling in astrocytes, this area of research rapidly emerged after the discovery of hypothalamic inflammation and gliosis in obese rodents and humans. Current studies have revealed the involvement of a wide variety of glial cell types in the modulation of neuronal activity, regulation of hormone and nutrient availability, and participation in the physiological regulation of feeding behaviour. In addition, one glial type, microglia, has recently been implicated in susceptibility to diet-induced obesity. Together, these exciting new findings deepen our understanding of energy homeostasis regulation and raise the possibility of identifying novel mechanisms that contribute to the pathogenesis of obesity.
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Literatur
1.
Zurück zum Zitat Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404:661–671PubMed Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404:661–671PubMed
2.
Zurück zum Zitat Barsh GS, Farooqi IS, O’Rahilly S (2000) Genetics of body-weight regulation. Nature 404:644–651PubMed Barsh GS, Farooqi IS, O’Rahilly S (2000) Genetics of body-weight regulation. Nature 404:644–651PubMed
3.
Zurück zum Zitat Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432PubMedCrossRef Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432PubMedCrossRef
5.
Zurück zum Zitat Thaler JP, Yi CX, Schur EA et al (2012) Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest 122:153–162PubMedCrossRef Thaler JP, Yi CX, Schur EA et al (2012) Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest 122:153–162PubMedCrossRef
6.
Zurück zum Zitat Valdearcos M, Robblee MM, Benjamin DI, Nomura DK, Xu AW, Koliwad SK (2014) Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function. Cell Rep 9:2124–2138PubMedPubMedCentralCrossRef Valdearcos M, Robblee MM, Benjamin DI, Nomura DK, Xu AW, Koliwad SK (2014) Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function. Cell Rep 9:2124–2138PubMedPubMedCentralCrossRef
7.
Zurück zum Zitat Valdearcos M, Xu AW, Koliwad SK (2015) Hypothalamic inflammation in the control of metabolic function. Annu Rev Physiol 77:131–160PubMedCrossRef Valdearcos M, Xu AW, Koliwad SK (2015) Hypothalamic inflammation in the control of metabolic function. Annu Rev Physiol 77:131–160PubMedCrossRef
8.
Zurück zum Zitat Thaler JP, Guyenet SJ, Dorfman MD, Wisse BE, Schwartz MW (2013) Hypothalamic inflammation: marker or mechanism of obesity pathogenesis? Diabetes 62:2629–2634PubMedPubMedCentralCrossRef Thaler JP, Guyenet SJ, Dorfman MD, Wisse BE, Schwartz MW (2013) Hypothalamic inflammation: marker or mechanism of obesity pathogenesis? Diabetes 62:2629–2634PubMedPubMedCentralCrossRef
9.
Zurück zum Zitat Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW (2006) Central nervous system control of food intake and body weight. Nature 443:289–295PubMedCrossRef Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW (2006) Central nervous system control of food intake and body weight. Nature 443:289–295PubMedCrossRef
10.
Zurück zum Zitat De Souza CT, Araujo EP, Bordin S et al (2005) Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology 146:4192–4199PubMedCrossRef De Souza CT, Araujo EP, Bordin S et al (2005) Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology 146:4192–4199PubMedCrossRef
11.
14.
Zurück zum Zitat Li JM, Ge CX, Xu MX et al (2015) Betaine recovers hypothalamic neural injury by inhibiting astrogliosis and inflammation in fructose-fed rats. Mol Nutr Food Res 59:189–202PubMedCrossRef Li JM, Ge CX, Xu MX et al (2015) Betaine recovers hypothalamic neural injury by inhibiting astrogliosis and inflammation in fructose-fed rats. Mol Nutr Food Res 59:189–202PubMedCrossRef
15.
Zurück zum Zitat Grayson BE, Levasseur PR, Williams SM, Smith MS, Marks DL, Grove KL (2010) Changes in melanocortin expression and inflammatory pathways in fetal offspring of nonhuman primates fed a high-fat diet. Endocrinology 151:1622–1632PubMedPubMedCentralCrossRef Grayson BE, Levasseur PR, Williams SM, Smith MS, Marks DL, Grove KL (2010) Changes in melanocortin expression and inflammatory pathways in fetal offspring of nonhuman primates fed a high-fat diet. Endocrinology 151:1622–1632PubMedPubMedCentralCrossRef
16.
Zurück zum Zitat Posey KA, Clegg DJ, Printz RL et al (2009) Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet. Am J Physiol Endocrinol Metab 296:E1003–E1012PubMedCrossRef Posey KA, Clegg DJ, Printz RL et al (2009) Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet. Am J Physiol Endocrinol Metab 296:E1003–E1012PubMedCrossRef
17.
Zurück zum Zitat Milanski M, Degasperi G, Coope A et al (2009) Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. J Neurosci 29:359–370 Milanski M, Degasperi G, Coope A et al (2009) Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. J Neurosci 29:359–370
18.
Zurück zum Zitat Morselli E, Fuente-Martin E, Finan B et al (2014) Hypothalamic PGC-1alpha protects against high-fat diet exposure by regulating ERalpha. Cell Rep 9:633–645PubMedPubMedCentralCrossRef Morselli E, Fuente-Martin E, Finan B et al (2014) Hypothalamic PGC-1alpha protects against high-fat diet exposure by regulating ERalpha. Cell Rep 9:633–645PubMedPubMedCentralCrossRef
19.
Zurück zum Zitat Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D (2008) Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell 135:61–73PubMedPubMedCentralCrossRef Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D (2008) Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell 135:61–73PubMedPubMedCentralCrossRef
20.
Zurück zum Zitat Munzberg H, Flier JS, Bjorbaek C (2004) Region-specific leptin resistance within the hypothalamus of diet-induced obese mice. Endocrinology 145:4880–4889PubMedCrossRef Munzberg H, Flier JS, Bjorbaek C (2004) Region-specific leptin resistance within the hypothalamus of diet-induced obese mice. Endocrinology 145:4880–4889PubMedCrossRef
21.
Zurück zum Zitat Kleinridders A, Schenten D, Konner AC et al (2009) MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. Cell Metab 10:249–259PubMedPubMedCentralCrossRef Kleinridders A, Schenten D, Konner AC et al (2009) MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. Cell Metab 10:249–259PubMedPubMedCentralCrossRef
22.
Zurück zum Zitat Hong J, Stubbins RE, Smith RR, Harvey AE, Nunez NP (2009) Differential susceptibility to obesity between male, female and ovariectomized female mice. Nutr J 8:11PubMedPubMedCentralCrossRef Hong J, Stubbins RE, Smith RR, Harvey AE, Nunez NP (2009) Differential susceptibility to obesity between male, female and ovariectomized female mice. Nutr J 8:11PubMedPubMedCentralCrossRef
23.
Zurück zum Zitat Gao Y, Ottaway N, Schriever SC et al (2014) Hormones and diet, but not body weight, control hypothalamic microglial activity. Glia 62:17–25PubMedCrossRef Gao Y, Ottaway N, Schriever SC et al (2014) Hormones and diet, but not body weight, control hypothalamic microglial activity. Glia 62:17–25PubMedCrossRef
24.
Zurück zum Zitat Garcia-Caceres C, Fuente-Martin E, Diaz F et al (2014) The opposing effects of ghrelin on hypothalamic and systemic inflammatory processes are modulated by its acylation status and food intake in male rats. Endocrinology 155:2868–2880PubMedCrossRef Garcia-Caceres C, Fuente-Martin E, Diaz F et al (2014) The opposing effects of ghrelin on hypothalamic and systemic inflammatory processes are modulated by its acylation status and food intake in male rats. Endocrinology 155:2868–2880PubMedCrossRef
25.
Zurück zum Zitat Wang X, Ge A, Cheng M et al (2012) Increased hypothalamic inflammation associated with the susceptibility to obesity in rats exposed to high-fat diet. Exp Diabetes Res 2012:847246PubMedPubMedCentral Wang X, Ge A, Cheng M et al (2012) Increased hypothalamic inflammation associated with the susceptibility to obesity in rats exposed to high-fat diet. Exp Diabetes Res 2012:847246PubMedPubMedCentral
26.
Zurück zum Zitat Barres BA (2008) The mystery and magic of glia: a perspective on their roles in health and disease. Neuron 60:430–440PubMedCrossRef Barres BA (2008) The mystery and magic of glia: a perspective on their roles in health and disease. Neuron 60:430–440PubMedCrossRef
27.
Zurück zum Zitat Pfrieger FW, Slezak M (2012) Genetic approaches to study glial cells in the rodent brain. Glia 60:681–701PubMedCrossRef Pfrieger FW, Slezak M (2012) Genetic approaches to study glial cells in the rodent brain. Glia 60:681–701PubMedCrossRef
28.
Zurück zum Zitat Wieghofer P, Prinz M (2016) Genetic manipulation of microglia during brain development and disease. Biochim Biophys Acta 1862:299–309PubMedCrossRef Wieghofer P, Prinz M (2016) Genetic manipulation of microglia during brain development and disease. Biochim Biophys Acta 1862:299–309PubMedCrossRef
29.
Zurück zum Zitat Goodman T, Hajihosseini MK (2015) Hypothalamic tanycytes-masters and servants of metabolic, neuroendocrine, and neurogenic functions. Front Neurosci 9:387PubMedPubMedCentralCrossRef Goodman T, Hajihosseini MK (2015) Hypothalamic tanycytes-masters and servants of metabolic, neuroendocrine, and neurogenic functions. Front Neurosci 9:387PubMedPubMedCentralCrossRef
30.
Zurück zum Zitat Fenno L, Yizhar O, Deisseroth K (2011) The development and application of optogenetics. Annu Rev Neurosci 34:389–412PubMedCrossRef Fenno L, Yizhar O, Deisseroth K (2011) The development and application of optogenetics. Annu Rev Neurosci 34:389–412PubMedCrossRef
31.
Zurück zum Zitat Sternson SM, Roth BL (2014) Chemogenetic tools to interrogate brain functions. Annu Rev Neurosci 37:387–407PubMedCrossRef Sternson SM, Roth BL (2014) Chemogenetic tools to interrogate brain functions. Annu Rev Neurosci 37:387–407PubMedCrossRef
32.
Zurück zum Zitat Yang L, Qi Y, Yang Y (2015) Astrocytes control food intake by inhibiting AGRP neuron activity via adenosine A1 receptors. Cell Rep 11:798–807PubMedCrossRef Yang L, Qi Y, Yang Y (2015) Astrocytes control food intake by inhibiting AGRP neuron activity via adenosine A1 receptors. Cell Rep 11:798–807PubMedCrossRef
33.
Zurück zum Zitat Ransohoff RM, Cardona AE (2010) The myeloid cells of the central nervous system parenchyma. Nature 468:253–262PubMedCrossRef Ransohoff RM, Cardona AE (2010) The myeloid cells of the central nervous system parenchyma. Nature 468:253–262PubMedCrossRef
34.
Zurück zum Zitat Ginhoux F, Greter M, Leboeuf M et al (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841–845PubMedPubMedCentralCrossRef Ginhoux F, Greter M, Leboeuf M et al (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841–845PubMedPubMedCentralCrossRef
35.
Zurück zum Zitat Ajami B, Bennett JL, Krieger C, McNagny KM, Rossi FM (2011) Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat Neurosci 14:1142–1149PubMedCrossRef Ajami B, Bennett JL, Krieger C, McNagny KM, Rossi FM (2011) Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat Neurosci 14:1142–1149PubMedCrossRef
37.
38.
Zurück zum Zitat Baufeld C, Osterloh A, Prokop S, Miller KR, Heppner FL (2016) High-fat diet-induced brain region-specific phenotypic spectrum of CNS resident microglia. Acta Neuropathol 132:361–375PubMedPubMedCentralCrossRef Baufeld C, Osterloh A, Prokop S, Miller KR, Heppner FL (2016) High-fat diet-induced brain region-specific phenotypic spectrum of CNS resident microglia. Acta Neuropathol 132:361–375PubMedPubMedCentralCrossRef
39.
Zurück zum Zitat Djogo T, Robins SC, Schneider S et al (2016) Adult NG2-Glia are required for median eminence-mediated leptin sensing and body weight control. Cell Metab 23:797–810PubMedCrossRef Djogo T, Robins SC, Schneider S et al (2016) Adult NG2-Glia are required for median eminence-mediated leptin sensing and body weight control. Cell Metab 23:797–810PubMedCrossRef
40.
Zurück zum Zitat Reis WL, Yi CX, Gao Y, Tschop MH, Stern JE (2015) Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior. Endocrinology 156:1303–1315PubMedPubMedCentralCrossRef Reis WL, Yi CX, Gao Y, Tschop MH, Stern JE (2015) Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior. Endocrinology 156:1303–1315PubMedPubMedCentralCrossRef
41.
43.
Zurück zum Zitat Cardona AE, Pioro EP, Sasse ME et al (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9:917–924PubMedCrossRef Cardona AE, Pioro EP, Sasse ME et al (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9:917–924PubMedCrossRef
44.
Zurück zum Zitat Morris DL, Oatmen KE, Wang T, DelProposto JL, Lumeng CN (2012) CX3CR1 deficiency does not influence trafficking of adipose tissue macrophages in mice with diet-induced obesity. Obesity 20:1189–1199PubMedPubMedCentralCrossRef Morris DL, Oatmen KE, Wang T, DelProposto JL, Lumeng CN (2012) CX3CR1 deficiency does not influence trafficking of adipose tissue macrophages in mice with diet-induced obesity. Obesity 20:1189–1199PubMedPubMedCentralCrossRef
45.
Zurück zum Zitat Polyak A, Ferenczi S, Denes A et al (2014) The fractalkine/Cx3CR1 system is implicated in the development of metabolic visceral adipose tissue inflammation in obesity. Brain Behav Immun 38:25–35PubMedCrossRef Polyak A, Ferenczi S, Denes A et al (2014) The fractalkine/Cx3CR1 system is implicated in the development of metabolic visceral adipose tissue inflammation in obesity. Brain Behav Immun 38:25–35PubMedCrossRef
46.
Zurück zum Zitat Morari J, Anhe GF, Nascimento LF et al (2014) Fractalkine (CX3CL1) is involved in the early activation of hypothalamic inflammation in experimental obesity. Diabetes 63:3770–3784PubMedCrossRef Morari J, Anhe GF, Nascimento LF et al (2014) Fractalkine (CX3CL1) is involved in the early activation of hypothalamic inflammation in experimental obesity. Diabetes 63:3770–3784PubMedCrossRef
48.
49.
Zurück zum Zitat Imai T, Hieshima K, Haskell C et al (1997) Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 91:521–530PubMedCrossRef Imai T, Hieshima K, Haskell C et al (1997) Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 91:521–530PubMedCrossRef
50.
Zurück zum Zitat Jung S, Aliberti J, Graemmel P et al (2000) Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol 20:4106–4114PubMedPubMedCentralCrossRef Jung S, Aliberti J, Graemmel P et al (2000) Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol 20:4106–4114PubMedPubMedCentralCrossRef
51.
Zurück zum Zitat Butovsky O, Jedrychowski MP, Moore CS et al (2014) Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat Neurosci 17:131–143PubMedCrossRef Butovsky O, Jedrychowski MP, Moore CS et al (2014) Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat Neurosci 17:131–143PubMedCrossRef
52.
Zurück zum Zitat Zhang Y, Chen K, Sloan SA et al (2014) An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci 34:11929–11947 Zhang Y, Chen K, Sloan SA et al (2014) An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci 34:11929–11947
53.
Zurück zum Zitat Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7–35PubMedCrossRef Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7–35PubMedCrossRef
54.
Zurück zum Zitat Garcia-Caceres C, Quarta C, Varela L et al (2016) Astrocytic insulin signaling couples brain glucose uptake with nutrient availability. Cell 166:867–880PubMedCrossRef Garcia-Caceres C, Quarta C, Varela L et al (2016) Astrocytic insulin signaling couples brain glucose uptake with nutrient availability. Cell 166:867–880PubMedCrossRef
55.
Zurück zum Zitat Rothstein JD, Dykes-Hoberg M, Pardo CA et al (1996) Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675–686PubMedCrossRef Rothstein JD, Dykes-Hoberg M, Pardo CA et al (1996) Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675–686PubMedCrossRef
56.
Zurück zum Zitat Cataldo AM, Broadwell RD (1986) Cytochemical identification of cerebral glycogen and glucose-6-phosphatase activity under normal and experimental conditions. II. Choroid plexus and ependymal epithelia, endothelia and pericytes. J Neurocytol 15:511–524PubMedCrossRef Cataldo AM, Broadwell RD (1986) Cytochemical identification of cerebral glycogen and glucose-6-phosphatase activity under normal and experimental conditions. II. Choroid plexus and ependymal epithelia, endothelia and pericytes. J Neurocytol 15:511–524PubMedCrossRef
57.
Zurück zum Zitat Leloup C, Arluison M, Lepetit N et al (1994) Glucose transporter 2 (GLUT 2): expression in specific brain nuclei. Brain Res 638:221–226PubMedCrossRef Leloup C, Arluison M, Lepetit N et al (1994) Glucose transporter 2 (GLUT 2): expression in specific brain nuclei. Brain Res 638:221–226PubMedCrossRef
58.
Zurück zum Zitat Suh SW, Bergher JP, Anderson CM, Treadway JL, Fosgerau K, Swanson RA (2007) Astrocyte glycogen sustains neuronal activity during hypoglycemia: studies with the glycogen phosphorylase inhibitor CP-316,819 ([R-R*, S*]-5-chloro-N-[2-hydroxy-3-(methoxymethylamino)-3-oxo-1-(phenylmethyl)pro pyl]-1H-indole-2-carboxamide). J Pharmacol Exp Ther 321:45–50PubMedCrossRef Suh SW, Bergher JP, Anderson CM, Treadway JL, Fosgerau K, Swanson RA (2007) Astrocyte glycogen sustains neuronal activity during hypoglycemia: studies with the glycogen phosphorylase inhibitor CP-316,819 ([R-R*, S*]-5-chloro-N-[2-hydroxy-3-(methoxymethylamino)-3-oxo-1-(phenylmethyl)pro pyl]-1H-indole-2-carboxamide). J Pharmacol Exp Ther 321:45–50PubMedCrossRef
59.
Zurück zum Zitat Brown AM, Sickmann HM, Fosgerau K et al (2005) Astrocyte glycogen metabolism is required for neural activity during aglycemia or intense stimulation in mouse white matter. J Neurosci Res 79:74–80PubMedCrossRef Brown AM, Sickmann HM, Fosgerau K et al (2005) Astrocyte glycogen metabolism is required for neural activity during aglycemia or intense stimulation in mouse white matter. J Neurosci Res 79:74–80PubMedCrossRef
62.
63.
Zurück zum Zitat Le Foll C, Dunn-Meynell AA, Miziorko HM, Levin BE (2014) Regulation of hypothalamic neuronal sensing and food intake by ketone bodies and fatty acids. Diabetes 63:1259–1269PubMedPubMedCentralCrossRef Le Foll C, Dunn-Meynell AA, Miziorko HM, Levin BE (2014) Regulation of hypothalamic neuronal sensing and food intake by ketone bodies and fatty acids. Diabetes 63:1259–1269PubMedPubMedCentralCrossRef
64.
Zurück zum Zitat Le Foll C, Levin BE (2016) Fatty acid-induced astrocyte ketone production and the control of food intake. Am J Physiol Regul Integr Comp Physiol 310:R1186–R1192PubMedCrossRef Le Foll C, Levin BE (2016) Fatty acid-induced astrocyte ketone production and the control of food intake. Am J Physiol Regul Integr Comp Physiol 310:R1186–R1192PubMedCrossRef
65.
Zurück zum Zitat Cheunsuang O, Morris R (2005) Astrocytes in the arcuate nucleus and median eminence that take up a fluorescent dye from the circulation express leptin receptors and neuropeptide Y Y1 receptors. Glia 52:228–233PubMedCrossRef Cheunsuang O, Morris R (2005) Astrocytes in the arcuate nucleus and median eminence that take up a fluorescent dye from the circulation express leptin receptors and neuropeptide Y Y1 receptors. Glia 52:228–233PubMedCrossRef
66.
Zurück zum Zitat Fuente-Martin E, Garcia-Caceres C, Granado M et al (2012) Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes. J Clin Invest 122:3900–3913PubMedPubMedCentralCrossRef Fuente-Martin E, Garcia-Caceres C, Granado M et al (2012) Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes. J Clin Invest 122:3900–3913PubMedPubMedCentralCrossRef
67.
Zurück zum Zitat Kim JG, Suyama S, Koch M et al (2014) Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding. Nat Neurosci 17:908–910PubMedCrossRef Kim JG, Suyama S, Koch M et al (2014) Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding. Nat Neurosci 17:908–910PubMedCrossRef
69.
Zurück zum Zitat Hsuchou H, He Y, Kastin AJ et al (2009) Obesity induces functional astrocytic leptin receptors in hypothalamus. Brain: J Neurol 132:889–902CrossRef Hsuchou H, He Y, Kastin AJ et al (2009) Obesity induces functional astrocytic leptin receptors in hypothalamus. Brain: J Neurol 132:889–902CrossRef
70.
Zurück zum Zitat Jayaram B, Pan W, Wang Y et al (1985) (2013) Astrocytic leptin-receptor knockout mice show partial rescue of leptin resistance in diet-induced obesity. J Appl Physiol 114:734–741CrossRef Jayaram B, Pan W, Wang Y et al (1985) (2013) Astrocytic leptin-receptor knockout mice show partial rescue of leptin resistance in diet-induced obesity. J Appl Physiol 114:734–741CrossRef
71.
Zurück zum Zitat Fuente-Martin E, Garcia-Caceres C, Argente-Arizon P et al (2016) Ghrelin regulates glucose and glutamate transporters in hypothalamic astrocytes. Sci Rep 6:23673PubMedPubMedCentralCrossRef Fuente-Martin E, Garcia-Caceres C, Argente-Arizon P et al (2016) Ghrelin regulates glucose and glutamate transporters in hypothalamic astrocytes. Sci Rep 6:23673PubMedPubMedCentralCrossRef
72.
Zurück zum Zitat Reiner DJ, Mietlicki-Baase EG, McGrath LE et al (2016) Astrocytes regulate GLP-1 receptor-mediated effects on energy balance. J Neurosci 36:3531–3540 Reiner DJ, Mietlicki-Baase EG, McGrath LE et al (2016) Astrocytes regulate GLP-1 receptor-mediated effects on energy balance. J Neurosci 36:3531–3540
73.
Zurück zum Zitat Chen N, Sugihara H, Kim J et al (2016) Direct modulation of GFAP-expressing glia in the arcuate nucleus bi-directionally regulates feeding. Elife 5, e18716PubMedPubMedCentral Chen N, Sugihara H, Kim J et al (2016) Direct modulation of GFAP-expressing glia in the arcuate nucleus bi-directionally regulates feeding. Elife 5, e18716PubMedPubMedCentral
74.
Zurück zum Zitat Guyenet SJ, Nguyen HT, Hwang BH, Schwartz MW, Baskin DG, Thaler JP (2013) High-fat diet feeding causes rapid, non-apoptotic cleavage of caspase-3 in astrocytes. Brain Res 1512:97–105PubMedPubMedCentralCrossRef Guyenet SJ, Nguyen HT, Hwang BH, Schwartz MW, Baskin DG, Thaler JP (2013) High-fat diet feeding causes rapid, non-apoptotic cleavage of caspase-3 in astrocytes. Brain Res 1512:97–105PubMedPubMedCentralCrossRef
75.
Zurück zum Zitat Buckman LB, Thompson MM, Lippert RN, Blackwell TS, Yull FE, Ellacott KL (2015) Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice. Mol Metab 4:58–63PubMedCrossRef Buckman LB, Thompson MM, Lippert RN, Blackwell TS, Yull FE, Ellacott KL (2015) Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice. Mol Metab 4:58–63PubMedCrossRef
76.
Zurück zum Zitat Buckman LB, Thompson MM, Moreno HN, Ellacott KL (2013) Regional astrogliosis in the mouse hypothalamus in response to obesity. J Comp Neurol 521:1322–1333PubMedPubMedCentralCrossRef Buckman LB, Thompson MM, Moreno HN, Ellacott KL (2013) Regional astrogliosis in the mouse hypothalamus in response to obesity. J Comp Neurol 521:1322–1333PubMedPubMedCentralCrossRef
77.
Zurück zum Zitat Berkseth KE, Guyenet SJ, Melhorn SJ et al (2014) Hypothalamic gliosis associated with high-fat diet feeding is reversible in mice: a combined immunohistochemical and magnetic resonance imaging study. Endocrinology 155:2858–2867PubMedPubMedCentralCrossRef Berkseth KE, Guyenet SJ, Melhorn SJ et al (2014) Hypothalamic gliosis associated with high-fat diet feeding is reversible in mice: a combined immunohistochemical and magnetic resonance imaging study. Endocrinology 155:2858–2867PubMedPubMedCentralCrossRef
78.
Zurück zum Zitat Lee D, Thaler JP, Berkseth KE, Melhorn SJ, Schwartz MW, Schur EA (2013) Longer T(2) relaxation time is a marker of hypothalamic gliosis in mice with diet-induced obesity. Am J Physiol Endocrinol Metab 304:E1245–E1250PubMedPubMedCentralCrossRef Lee D, Thaler JP, Berkseth KE, Melhorn SJ, Schwartz MW, Schur EA (2013) Longer T(2) relaxation time is a marker of hypothalamic gliosis in mice with diet-induced obesity. Am J Physiol Endocrinol Metab 304:E1245–E1250PubMedPubMedCentralCrossRef
79.
Zurück zum Zitat Schur EA, Melhorn SJ, Oh SK et al (2015) Radiologic evidence that hypothalamic gliosis is associated with obesity and insulin resistance in humans. Obesity 23:2142–2148PubMedPubMedCentralCrossRef Schur EA, Melhorn SJ, Oh SK et al (2015) Radiologic evidence that hypothalamic gliosis is associated with obesity and insulin resistance in humans. Obesity 23:2142–2148PubMedPubMedCentralCrossRef
81.
Zurück zum Zitat Bull C, Freitas KC, Zou S et al (2014) Rat nucleus accumbens core astrocytes modulate reward and the motivation to self-administer ethanol after abstinence. Neuropsychopharmacol 39:2835–2845 Bull C, Freitas KC, Zou S et al (2014) Rat nucleus accumbens core astrocytes modulate reward and the motivation to self-administer ethanol after abstinence. Neuropsychopharmacol 39:2835–2845
82.
Zurück zum Zitat Horvath TL, Sarman B, Garcia-Caceres C et al (2010) Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proc Natl Acad Sci U S A 107:14875–14880PubMedPubMedCentralCrossRef Horvath TL, Sarman B, Garcia-Caceres C et al (2010) Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proc Natl Acad Sci U S A 107:14875–14880PubMedPubMedCentralCrossRef
83.
Zurück zum Zitat Elizondo-Vega R, Cortes-Campos C, Barahona MJ, Oyarce KA, Carril CA, Garcia-Robles MA (2015) The role of tanycytes in hypothalamic glucosensing. J Cell Mol Med 19:1471–1482PubMedPubMedCentralCrossRef Elizondo-Vega R, Cortes-Campos C, Barahona MJ, Oyarce KA, Carril CA, Garcia-Robles MA (2015) The role of tanycytes in hypothalamic glucosensing. J Cell Mol Med 19:1471–1482PubMedPubMedCentralCrossRef
84.
Zurück zum Zitat Morgello S, Uson RR, Schwartz EJ, Haber RS (1995) The human blood-brain barrier glucose transporter (GLUT1) is a glucose transporter of gray matter astrocytes. Glia 14:43–54PubMedCrossRef Morgello S, Uson RR, Schwartz EJ, Haber RS (1995) The human blood-brain barrier glucose transporter (GLUT1) is a glucose transporter of gray matter astrocytes. Glia 14:43–54PubMedCrossRef
85.
Zurück zum Zitat Garcia M, Millan C, Balmaceda-Aguilera C et al (2003) Hypothalamic ependymal-glial cells express the glucose transporter GLUT2, a protein involved in glucose sensing. J Neurochem 86:709–724PubMedCrossRef Garcia M, Millan C, Balmaceda-Aguilera C et al (2003) Hypothalamic ependymal-glial cells express the glucose transporter GLUT2, a protein involved in glucose sensing. J Neurochem 86:709–724PubMedCrossRef
86.
Zurück zum Zitat Millan C, Martinez F, Cortes-Campos C et al (2010) Glial glucokinase expression in adult and post-natal development of the hypothalamic region. ASN Neuro 2:e00035PubMedPubMedCentralCrossRef Millan C, Martinez F, Cortes-Campos C et al (2010) Glial glucokinase expression in adult and post-natal development of the hypothalamic region. ASN Neuro 2:e00035PubMedPubMedCentralCrossRef
87.
Zurück zum Zitat Cortes-Campos C, Elizondo R, Llanos P, Uranga RM, Nualart F, Garcia MA (2011) MCT expression and lactate influx/efflux in tanycytes involved in glia-neuron metabolic interaction. PLoS One 6:e16411PubMedPubMedCentralCrossRef Cortes-Campos C, Elizondo R, Llanos P, Uranga RM, Nualart F, Garcia MA (2011) MCT expression and lactate influx/efflux in tanycytes involved in glia-neuron metabolic interaction. PLoS One 6:e16411PubMedPubMedCentralCrossRef
88.
Zurück zum Zitat Langlet F, Levin BE, Luquet S et al (2013) Tanycytic VEGF-A boosts blood-hypothalamus barrier plasticity and access of metabolic signals to the arcuate nucleus in response to fasting. Cell Metab 17:607–617PubMedPubMedCentralCrossRef Langlet F, Levin BE, Luquet S et al (2013) Tanycytic VEGF-A boosts blood-hypothalamus barrier plasticity and access of metabolic signals to the arcuate nucleus in response to fasting. Cell Metab 17:607–617PubMedPubMedCentralCrossRef
89.
90.
Zurück zum Zitat Lee DA, Bedont JL, Pak T et al (2012) Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche. Nat Neurosci 15:700–702PubMedPubMedCentralCrossRef Lee DA, Bedont JL, Pak T et al (2012) Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche. Nat Neurosci 15:700–702PubMedPubMedCentralCrossRef
91.
Zurück zum Zitat Robins SC, Stewart I, McNay DE et al (2013) Alpha-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors. Nat Commun 4:2049PubMedCrossRef Robins SC, Stewart I, McNay DE et al (2013) Alpha-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors. Nat Commun 4:2049PubMedCrossRef
92.
93.
Zurück zum Zitat Levine JM, Stallcup WB (1987) Plasticity of developing cerebellar cells in vitro studied with antibodies against the NG2 antigen. J Neurosci 7:2721–2731 Levine JM, Stallcup WB (1987) Plasticity of developing cerebellar cells in vitro studied with antibodies against the NG2 antigen. J Neurosci 7:2721–2731
95.
Zurück zum Zitat Rhee W, Ray S, Yokoo H et al (2009) Quantitative analysis of mitotic Olig2 cells in adult human brain and gliomas: implications for glioma histogenesis and biology. Glia 57:510–523PubMedPubMedCentralCrossRef Rhee W, Ray S, Yokoo H et al (2009) Quantitative analysis of mitotic Olig2 cells in adult human brain and gliomas: implications for glioma histogenesis and biology. Glia 57:510–523PubMedPubMedCentralCrossRef
96.
Zurück zum Zitat Geha S, Pallud J, Junier MP et al (2010) NG2+/Olig2+ cells are the major cycle-related cell population of the adult human normal brain. Brain Pathol 20:399–411PubMedCrossRef Geha S, Pallud J, Junier MP et al (2010) NG2+/Olig2+ cells are the major cycle-related cell population of the adult human normal brain. Brain Pathol 20:399–411PubMedCrossRef
97.
Zurück zum Zitat Nishiyama A, Komitova M, Suzuki R, Zhu X (2009) Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nat Rev Neurosci 10:9–22PubMedCrossRef Nishiyama A, Komitova M, Suzuki R, Zhu X (2009) Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nat Rev Neurosci 10:9–22PubMedCrossRef
98.
99.
Zurück zum Zitat Mueller K, Anwander A, Moller HE et al (2011) Sex-dependent influences of obesity on cerebral white matter investigated by diffusion-tensor imaging. PLoS One 6:e18544PubMedPubMedCentralCrossRef Mueller K, Anwander A, Moller HE et al (2011) Sex-dependent influences of obesity on cerebral white matter investigated by diffusion-tensor imaging. PLoS One 6:e18544PubMedPubMedCentralCrossRef
100.
Zurück zum Zitat Stanek KM, Grieve SM, Brickman AM et al (2011) Obesity is associated with reduced white matter integrity in otherwise healthy adults. Obesity 19:500–504PubMedCrossRef Stanek KM, Grieve SM, Brickman AM et al (2011) Obesity is associated with reduced white matter integrity in otherwise healthy adults. Obesity 19:500–504PubMedCrossRef
101.
Zurück zum Zitat Karlsson HK, Tuulari JJ, Hirvonen J et al (2013) Obesity is associated with white matter atrophy: a combined diffusion tensor imaging and voxel-based morphometric study. Obesity 21:2530–2537PubMedCrossRef Karlsson HK, Tuulari JJ, Hirvonen J et al (2013) Obesity is associated with white matter atrophy: a combined diffusion tensor imaging and voxel-based morphometric study. Obesity 21:2530–2537PubMedCrossRef
102.
Zurück zum Zitat Yokum S, Ng J, Stice E (2012) Relation of regional gray and white matter volumes to current BMI and future increases in BMI: a prospective MRI study. Int J Obes 36:656–664CrossRef Yokum S, Ng J, Stice E (2012) Relation of regional gray and white matter volumes to current BMI and future increases in BMI: a prospective MRI study. Int J Obes 36:656–664CrossRef
103.
Zurück zum Zitat Shott ME, Cornier MA, Mittal VA et al (2015) Orbitofrontal cortex volume and brain reward response in obesity. Int J Obes 39:214–221CrossRef Shott ME, Cornier MA, Mittal VA et al (2015) Orbitofrontal cortex volume and brain reward response in obesity. Int J Obes 39:214–221CrossRef
104.
Zurück zum Zitat Puig J, Blasco G, Daunis IEJ et al (2015) Hypothalamic damage is associated with inflammatory markers and worse cognitive performance in obese subjects. J Clin Endocrinol Metab 100:E276–E281PubMedCrossRef Puig J, Blasco G, Daunis IEJ et al (2015) Hypothalamic damage is associated with inflammatory markers and worse cognitive performance in obese subjects. J Clin Endocrinol Metab 100:E276–E281PubMedCrossRef
105.
Zurück zum Zitat Cazettes F, Cohen JI, Yau PL, Talbot H, Convit A (2011) Obesity-mediated inflammation may damage the brain circuit that regulates food intake. Brain Res 1373:101–109PubMedCrossRef Cazettes F, Cohen JI, Yau PL, Talbot H, Convit A (2011) Obesity-mediated inflammation may damage the brain circuit that regulates food intake. Brain Res 1373:101–109PubMedCrossRef
106.
107.
Zurück zum Zitat Zhang Y, Sloan SA, Clarke LE et al (2016) Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron 89:37–53PubMedCrossRef Zhang Y, Sloan SA, Clarke LE et al (2016) Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron 89:37–53PubMedCrossRef
108.
Zurück zum Zitat Han X, Chen M, Wang F et al (2013) Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice. Cell Stem Cell 12:342–353PubMedPubMedCentralCrossRef Han X, Chen M, Wang F et al (2013) Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice. Cell Stem Cell 12:342–353PubMedPubMedCentralCrossRef
Metadaten
Titel
Glia: silent partners in energy homeostasis and obesity pathogenesis
verfasst von
John D. Douglass
Mauricio D. Dorfman
Joshua P. Thaler
Publikationsdatum
16.12.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Diabetologia / Ausgabe 2/2017
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-016-4181-3

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