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Acta Neuropathologica
Erschienen in: Acta Neuropathologica 1/2014

01.01.2014 | Review

The neuropathology of obesity: insights from human disease

verfasst von: Edward B. Lee, Mark P. Mattson

Erschienen in: Acta Neuropathologica | Ausgabe 1/2014

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Abstract

Obesity, a pathologic state defined by excess adipose tissue, is a significant public health problem as it affects a large proportion of individuals and is linked with increased risk for numerous chronic diseases. Obesity is the result of fundamental changes associated with modern society including overnutrition and sedentary lifestyles. Proper energy homeostasis is dependent on normal brain function as the master metabolic regulator, which integrates peripheral signals, modulates autonomic outflow and controls feeding behavior. Therefore, many human brain diseases are associated with obesity. This review explores the neuropathology of obesity by examining brain diseases which either cause or are influenced by obesity. First, several genetic and acquired brain diseases are discussed as a means to understand the central regulation of peripheral metabolism. These diseases range from monogenetic causes of obesity (leptin deficiency, MC4R deficiency, Bardet–Biedl syndrome and others) to complex neurodevelopmental disorders (Prader–Willi syndrome and Sim1 deficiency) and neurodegenerative conditions (frontotemporal dementia and Gourmand’s syndrome) and serve to highlight the central regulatory mechanisms which have evolved to maintain energy homeostasis. Next, to examine the effect of obesity on the brain, chronic neuropathologic conditions (epilepsy, multiple sclerosis and Alzheimer’s disease) are discussed as examples of obesity leading to maladaptive processes which exacerbate chronic disease. Thus, obesity is associated with multiple pathways including abnormal metabolism, altered hormonal signaling and increased inflammation which act in concert to promote downstream neuropathology. Finally, the effect of anti-obesity interventions is discussed in terms of brain structure and function. Together, understanding human diseases and anti-obesity interventions leads to insights into the bidirectional interaction between peripheral metabolism and central brain function, highlighting the need for continued clinicopathologic and mechanistic studies of the neuropathology of obesity.
Literatur
1.
2.
3.
Ahima RS, Bjorbaek C, Osei S, Flier JS (1999) Regulation of neuronal and glial proteins by leptin: implications for brain development. Endocrinology 140(6):2755–2762PubMedCrossRef
4.
Ahima RS, Hileman SM (2000) Postnatal regulation of hypothalamic neuropeptide expression by leptin: implications for energy balance and body weight regulation. Regul Pept 92(1–3):1–7PubMedCrossRef
5.
Ahima RS, Prabakaran D, Flier JS (1998) Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding. Implications for energy homeostasis and neuroendocrine function. J Clin Invest 101(5):1020–1027. doi:10.​1172/​JCI1176 PubMedCentralPubMedCrossRef
6.
Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS (1996) Role of leptin in the neuroendocrine response to fasting. Nature 382(6588):250–252. doi:10.​1038/​382250a0 PubMedCrossRef
7.
Ahituv N, Kavaslar N, Schackwitz W, Ustaszewska A, Martin J, Hebert S, Doelle H, Ersoy B, Kryukov G, Schmidt S, Yosef N, Ruppin E, Sharan R, Vaisse C, Sunyaev S, Dent R, Cohen J, McPherson R, Pennacchio LA (2007) Medical sequencing at the extremes of human body mass. Am J Hum Genet 80(4):779–791. doi:10.​1086/​513471 PubMedCentralPubMedCrossRef
8.
Aksoy A, Karaguzel G, Akbulut U, Turk A (2011) Two sisters with Bardet–Biedl syndrome: brain abnormalities and unusual facial findings. Turk J Pediatr 53(4):460–463PubMed
9.
10.
11.
Alharbi KK, Spanakis E, Tan K, Smith MJ, Aldahmesh MA, O’Dell SD, Sayer AA, Lawlor DA, Ebrahim S, Davey Smith G, O’Rahilly S, Farooqi S, Cooper C, Phillips DI, Day IN (2007) Prevalence and functionality of paucimorphic and private MC4R mutations in a large, unselected European British population, scanned by meltMADGE. Hum Mutat 28(3):294–302. doi:10.​1002/​humu.​20404 PubMedCrossRef
12.
Anand BK, Brobeck JR (1951) Localization of a “feeding center” in the hypothalamus of the rat. Proc Soc Exp Biol Med 77(2):323–324PubMedCrossRef
13.
Arletti R, Benelli A, Bertolini A (1990) Oxytocin inhibits food and fluid intake in rats. Physiol Behav 48(6):825–830PubMedCrossRef
14.
15.
Arunabh S, Pollack S, Yeh J, Aloia JF (2003) Body fat content and 25-hydroxyvitamin D levels in healthy women. J Clin Endocrinol Metab 88(1):157–161PubMedCrossRef
16.
17.
18.
19.
20.
Babinski JP (1993) Tumor of the body of the pituitary without acromegaly and with arrest of development of the genital organs. 1900. Obes Res 1(4):332–333PubMedCrossRef
21.
Baicy K, London ED, Monterosso J, Wong ML, Delibasi T, Sharma A, Licinio J (2007) Leptin replacement alters brain response to food cues in genetically leptin-deficient adults. Proc Natl Acad Sci USA 104(46):18276–18279. doi:10.​1073/​pnas.​0706481104 PubMedCrossRef
22.
Bailey AR, von Engelhardt N, Leng G, Smith RG, Dickson SL (2000) Growth hormone secretagogue activation of the arcuate nucleus and brainstem occurs via a non-noradrenergic pathway. J Neuroendocrinol 12(3):191–197PubMedCrossRef
23.
Baker K, Northam GB, Chong WK, Banks T, Beales P, Baldeweg T (2011) Neocortical and hippocampal volume loss in a human ciliopathy: a quantitative MRI study in Bardet–Biedl syndrome. Am J Med Genet A 155A(1):1–8. doi:10.​1002/​ajmg.​a.​33773 PubMedCrossRef
24.
25.
Barrett-Connor E (1996) The menopause, hormone replacement, and cardiovascular disease: the epidemiologic evidence. Maturitas 23(2):227–234PubMedCrossRef
26.
Baskin E, Kayiran SM, Oto S, Alehan F, Agildere AM, Saatci U (2002) Cerebellar vermis hypoplasia in a patient with Bardet–Biedl syndrome. J Child Neurol 17(5):385–387PubMedCrossRef
27.
Beeri MS, Silverman JM, Davis KL, Marin D, Grossman HZ, Schmeidler J, Purohit DP, Perl DP, Davidson M, Mohs RC, Haroutunian V (2005) Type 2 diabetes is negatively associated with Alzheimer’s disease neuropathology. J Gerontol A Biol Sci Med Sci 60(4):471–475PubMedCentralPubMedCrossRef
28.
29.
Bennouna-Greene V, Kremer S, Stoetzel C, Christmann D, Schuster C, Durand M, Verloes A, Sigaudy S, Holder-Espinasse M, Godet J, Brandt C, Marion V, Danion A, Dietemann JL, Dollfus H (2011) Hippocampal dysgenesis and variable neuropsychiatric phenotypes in patients with Bardet–Biedl syndrome underline complex CNS impact of primary cilia. Clin Genet 80(6):523–531. doi:10.​1111/​j.​1399-0004.​2011.​01688.​x PubMedCrossRef
30.
Berbari NF, Pasek RC, Malarkey EB, Yazdi SM, McNair AD, Lewis WR, Nagy TR, Kesterson RA, Yoder BK (2013) Leptin resistance is a secondary consequence of the obesity in ciliopathy mutant mice. Proc Natl Acad Sci USA. doi:10.​1073/​pnas.​1210192110 PubMed
31.
32.
Biag J, Huang Y, Gou L, Hintiryan H, Askarinam A, Hahn JD, Toga AW, Dong HW (2012) Cyto- and chemoarchitecture of the hypothalamic paraventricular nucleus in the C57BL/6J male mouse: a study of immunostaining and multiple fluorescent tract tracing. J Comp Neurol 520(1):6–33. doi:10.​1002/​cne.​22698 PubMedCrossRef
33.
Biton V, Mirza W, Montouris G, Vuong A, Hammer AE, Barrett PS (2001) Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy. Neurology 56(2):172–177PubMedCrossRef
34.
35.
36.
Bray GA (1993) Commentary on classics of obesity. 4. Hypothalamic obesity. Obes Res 1(4):325–328PubMedCrossRef
37.
38.
Bruce-Keller AJ, Umberger G, McFall R, Mattson MP (1999) Food restriction reduces brain damage and improves behavioral outcome following excitotoxic and metabolic insults. Ann Neurol 45(1):8–15PubMedCrossRef
39.
Bruch H (1993) The Frohlich syndrome: report of the original case. 1939. Obes Res 1(4):329–331PubMedCrossRef
40.
41.
42.
43.
44.
45.
Cantorna MT, Hayes CE, DeLuca HF (1996) 1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci USA 93(15):7861–7864PubMedCrossRef
46.
47.
Challis BG, Pritchard LE, Creemers JW, Delplanque J, Keogh JM, Luan J, Wareham NJ, Yeo GS, Bhattacharyya S, Froguel P, White A, Farooqi IS, O’Rahilly S (2002) A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism. Hum Mol Genet 11(17):1997–2004PubMedCrossRef
48.
49.
Church C, Moir L, McMurray F, Girard C, Banks GT, Teboul L, Wells S, Bruning JC, Nolan PM, Ashcroft FM, Cox RD (2010) Overexpression of Fto leads to increased food intake and results in obesity. Nat Genet 42(12):1086–1092. doi:10.​1038/​ng.​713 PubMedCentralPubMedCrossRef
50.
Clancy B, Darlington RB, Finlay BL (2001) Translating developmental time across mammalian species. Neuroscience 105(1):7–17PubMedCrossRef
51.
Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A, Bougneres P, Lebouc Y, Froguel P, Guy-Grand B (1998) A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392(6674):398–401. doi:10.​1038/​32911 PubMedCrossRef
52.
Cockerell OC, Eckle I, Goodridge DM, Sander JW, Shorvon SD (1995) Epilepsy in a population of 6000 re-examined: secular trends in first attendance rates, prevalence, and prognosis. J Neurol Neurosurg Psychiatry 58(5):570–576PubMedCrossRef
53.
Compston JE, Vedi S, Ledger JE, Webb A, Gazet JC, Pilkington TR (1981) Vitamin D status and bone histomorphometry in gross obesity. Am J Clin Nutr 34(11):2359–2363PubMed
54.
55.
56.
57.
Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ (2002) Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 346(21):1623–1630. doi:10.​1056/​NEJMoa012908 PubMedCrossRef
58.
Cushing H (1994) The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). 1932. Obes Res 2(5):486–508PubMedCrossRef
59.
Cutler RG, Kelly J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, Troncoso JC, Mattson MP (2004) Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer’s disease. Proc Natl Acad Sci USA 101(7):2070–2075. doi:10.​1073/​pnas.​0305799101 PubMedCrossRef
60.
Ogden CL, Carroll MD, Kit BK, Flegal KM (2012) Prevalence of obesity in the United States, 2009–2010. NCHS Data Brief 82:1–7PubMed
61.
62.
63.
64.
65.
66.
Drake C, Boutin H, Jones MS, Denes A, McColl BW, Selvarajah JR, Hulme S, Georgiou RF, Hinz R, Gerhard A, Vail A, Prenant C, Julyan P, Maroy R, Brown G, Smigova A, Herholz K, Kassiou M, Crossman D, Francis S, Proctor SD, Russell JC, Hopkins SJ, Tyrrell PJ, Rothwell NJ, Allan SM (2011) Brain inflammation is induced by co-morbidities and risk factors for stroke. Brain Behav Immun 25(6):1113–1122. doi:10.​1016/​j.​bbi.​2011.​02.​008 PubMedCentralPubMedCrossRef
67.
Duan W, Guo Z, Jiang H, Ware M, Li XJ, Mattson MP (2003) Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice. Proc Natl Acad Sci USA 100(5):2911–2916. doi:10.​1073/​pnas.​0536856100 PubMedCrossRef
68.
Duan W, Guo Z, Mattson MP (2001) Brain-derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice. J Neurochem 76(2):619–626PubMedCrossRef
69.
Duan W, Mattson MP (1999) Dietary restriction and 2-deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson’s disease. J Neurosci Res 57(2):195–206PubMedCrossRef
70.
71.
Elia M, Folmer P, Schlatmann A, Goren A, Austin S (1988) Carbohydrate, fat, and protein metabolism in muscle and in the whole body after mixed meal ingestion. Metabolism 37(6):542–551PubMedCrossRef
72.
73.
74.
Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF (2011) Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci USA 108(7):3017–3022. doi:10.​1073/​pnas.​1015950108 PubMedCrossRef
75.
Ewers M, Schmitz S, Hansson O, Walsh C, Fitzpatrick A, Bennett D, Minthon L, Trojanowski JQ, Shaw LM, Faluyi YO, Vellas B, Dubois B, Blennow K, Buerger K, Teipel SJ, Weiner M, Hampel H (2012) Body mass index is associated with biological CSF markers of core brain pathology of Alzheimer’s disease. Neurobiol Aging 33(8):1599–1608. doi:10.​1016/​j.​neurobiolaging.​2011.​05.​005 PubMedCentralPubMedCrossRef
76.
Faivre L, Cormier-Daire V, Lapierre JM, Colleaux L, Jacquemont S, Genevieve D, Saunier P, Munnich A, Turleau C, Romana S, Prieur M, De Blois MC, Vekemans M (2002) Deletion of the SIM1 gene (6q16.2) in a patient with a Prader–Willi-like phenotype. J Med Genet 39(8):594–596PubMedCrossRef
77.
78.
79.
Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, Hughes IA, McCamish MA, O’Rahilly S (1999) Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 341(12):879–884. doi:10.​1056/​NEJM199909163411​204 PubMedCrossRef
80.
Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, Sanna V, Jebb SA, Perna F, Fontana S, Lechler RI, DePaoli AM, O’Rahilly S (2002) Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 110(8):1093–1103. doi:10.​1172/​JCI15693 PubMedCentralPubMed
81.
82.
Feuillan PP, Ng D, Han JC, Sapp JC, Wetsch K, Spaulding E, Zheng YC, Caruso RC, Brooks BP, Johnston JJ, Yanovski JA, Biesecker LG (2011) Patients with Bardet–Biedl syndrome have hyperleptinemia suggestive of leptin resistance. J Clin Endocrinol Metab 96(3):E528–E535. doi:10.​1210/​jc.​2010-2290 PubMedCrossRef
83.
84.
85.
86.
87.
88.
Frisullo G, Mirabella M, Angelucci F, Caggiula M, Morosetti R, Sancricca C, Patanella AK, Nociti V, Iorio R, Bianco A, Tomassini V, Pozzilli C, Tonali PA, Matarese G, Batocchi AP (2007) The effect of disease activity on leptin, leptin receptor and suppressor of cytokine signalling-3 expression in relapsing-remitting multiple sclerosis. J Neuroimmunol 192(1–2):174–183. doi:10.​1016/​j.​jneuroim.​2007.​08.​008 PubMedCrossRef
89.
Froidevaux F, Schutz Y, Christin L, Jequier E (1993) Energy expenditure in obese women before and during weight loss, after refeeding, and in the weight-relapse period. Am J Clin Nutr 57(1):35–42PubMed
90.
Galgani J, Ravussin E (2011) Principles of human energy metabolism. In: Ahima RS (ed) Metabolic basis of obesity. Springer, New York, pp 1–23CrossRef
91.
Gerken T, Girard CA, Tung YC, Webby CJ, Saudek V, Hewitson KS, Yeo GS, McDonough MA, Cunliffe S, McNeill LA, Galvanovskis J, Rorsman P, Robins P, Prieur X, Coll AP, Ma M, Jovanovic Z, Farooqi IS, Sedgwick B, Barroso I, Lindahl T, Ponting CP, Ashcroft FM, O’Rahilly S, Schofield CJ (2007) The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318(5855):1469–1472. doi:10.​1126/​science.​1151710 PubMedCentralPubMedCrossRef
92.
93.
Gilhuis HJ, van Ravenswaaij CM, Hamel BJ, Gabreels FJ (2000) Interstitial 6q deletion with a Prader–Willi-like phenotype: a new case and review of the literature. Eur J Paediatr Neurol 4(1):39–43. doi:10.​1053/​ejpn.​1999.​0259 PubMedCrossRef
94.
Gillette Guyonnet S, Abellan Van Kan G, Alix E, Andrieu S, Belmin J, Berrut G, Bonnefoy M, Brocker P, Constans T, Ferry M, Ghisolfi-Marque A, Girard L, Gonthier R, Guerin O, Hervy MP, Jouanny P, Laurain MC, Lechowski L, Nourhashemi F, Raynaud-Simon A, Ritz P, Roche J, Rolland Y, Salva T, Vellas B (2007) IANA (International Academy on Nutrition and Aging) Expert Group: weight loss and Alzheimer’s disease. J Nutr Health Aging 11(1):38–48PubMed
95.
Gold RM (1973) Hypothalamic obesity: the myth of the ventromedial nucleus. Science 182(4111):488–490PubMedCrossRef
96.
97.
98.
Green JS, Parfrey PS, Harnett JD, Farid NR, Cramer BC, Johnson G, Heath O, McManamon PJ, O’Leary E, Pryse-Phillips W (1989) The cardinal manifestations of Bardet–Biedl syndrome, a form of Laurence–Moon–Biedl syndrome. N Engl J Med 321(15):1002–1009. doi:10.​1056/​NEJM198910123211​503 PubMedCrossRef
99.
Griffioen KJ, Wan R, Brown TR, Okun E, Camandola S, Mughal MR, Phillips TM, Mattson MP (2012) Aberrant heart rate and brainstem brain-derived neurotrophic factor (BDNF) signaling in a mouse model of Huntington’s disease. Neurobiol Aging 33(7):1481.e1–1481.e5. doi:10.​1016/​j.​neurobiolaging.​2011.​11.​030 CrossRef
100.
101.
Grundman M, Corey-Bloom J, Jernigan T, Archibald S, Thal LJ (1996) Low body weight in Alzheimer’s disease is associated with mesial temporal cortex atrophy. Neurology 46(6):1585–1591PubMedCrossRef
102.
Guan XM, Yu H, Palyha OC, McKee KK, Feighner SD, Sirinathsinghji DJ, Smith RG, Van der Ploeg LH, Howard AD (1997) Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res Mol Brain Res 48(1):23–29PubMedCrossRef
103.
104.
105.
Gwon AR, Park JS, Arumugam TV, Kwon YK, Chan SL, Kim SH, Baik SH, Yang S, Yun YK, Choi Y, Kim S, Tang SC, Hyun DH, Cheng A, Dann CE 3rd, Bernier M, Lee J, Markesbery WR, Mattson MP, Jo DG (2012) Oxidative lipid modification of nicastrin enhances amyloidogenic gamma-secretase activity in Alzheimer’s disease. Aging Cell 11(4):559–568. doi:10.​1111/​j.​1474-9726.​2012.​00817.​x PubMedCrossRef
106.
Halagappa VK, Guo Z, Pearson M, Matsuoka Y, Cutler RG, Laferla FM, Mattson MP (2007) Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer’s disease. Neurobiol Dis 26(1):212–220. doi:10.​1016/​j.​nbd.​2006.​12.​019 PubMedCrossRef
107.
108.
Han JC, Liu QR, Jones M, Levinn RL, Menzie CM, Jefferson-George KS, Adler-Wailes DC, Sanford EL, Lacbawan FL, Uhl GR, Rennert OM, Yanovski JA (2008) Brain-derived neurotrophic factor and obesity in the WAGR syndrome. N Engl J Med 359(9):918–927. doi:10.​1056/​NEJMoa0801119 PubMedCentralPubMedCrossRef
109.
Han JC, Muehlbauer MJ, Cui HN, Newgard CB, Haqq AM (2010) Lower brain-derived neurotrophic factor in patients with Prader–Willi syndrome compared to obese and lean control subjects. J Clin Endocrinol Metab 95(7):3532–3536. doi:10.​1210/​jc.​2010-0127 PubMedCrossRef
110.
111.
112.
Hauser WA, Annegers JF, Kurland LT (1993) Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984. Epilepsia 34(3):453–468PubMedCrossRef
113.
Hayes CE, Nashold FE, Spach KM, Pedersen LB (2003) The immunological functions of the vitamin D endocrine system. Cell Mol Biol 49(2):277–300PubMed
114.
Heitner J, Dickson D (1997) Diabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects. A retrospective postmortem immunocytochemical and histofluorescent study. Neurology 49(5):1306–1311PubMedCrossRef
115.
Hey H, Stokholm KH, Lund B, Sorensen OH (1982) Vitamin D deficiency in obese patients and changes in circulating vitamin D metabolites following jejunoileal bypass. Int J Obes 6(5):473–479PubMed
116.
Ho AJ, Stein JL, Hua X, Lee S, Hibar DP, Leow AD, Dinov ID, Toga AW, Saykin AJ, Shen L, Foroud T, Pankratz N, Huentelman MJ, Craig DW, Gerber JD, Allen AN, Corneveaux JJ, Stephan DA, DeCarli CS, DeChairo BM, Potkin SG, Jack CR Jr, Weiner MW, Raji CA, Lopez OL, Becker JT, Carmichael OT, Thompson PM (2010) A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly. Proc Natl Acad Sci USA 107(18):8404–8409. doi:10.​1073/​pnas.​0910878107 PubMedCrossRef
117.
Holder JL Jr, Butte NF, Zinn AR (2000) Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. Hum Mol Genet 9(1):101–108PubMedCrossRef
118.
119.
120.
Jaquet D, Leger J, Levy-Marchal C, Oury JF, Czernichow P (1998) Ontogeny of leptin in human fetuses and newborns: effect of intrauterine growth retardation on serum leptin concentrations. J Clin Endocrinol Metab 83(4):1243–1246PubMedCrossRef
121.
122.
Karamanakos SN, Vagenas K, Kalfarentzos F, Alexandrides TK (2008) Weight loss, appetite suppression, and changes in fasting and postprandial ghrelin and peptide-YY levels after Roux-en-Y gastric bypass and sleeve gastrectomy: a prospective, double blind study. Ann Surg 247(3):401–407. doi:10.​1097/​SLA.​0b013e318156f012​ PubMedCrossRef
123.
124.
125.
126.
127.
128.
Kleinridders A, Schenten D, Konner AC, Belgardt BF, Mauer J, Okamura T, Wunderlich FT, Medzhitov R, Bruning JC (2009) MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. Cell Metab 10(4):249–259. doi:10.​1016/​j.​cmet.​2009.​08.​013 PubMedCrossRef
129.
Kopin AS, Mathes WF, McBride EW, Nguyen M, Al-Haider W, Schmitz F, Bonner-Weir S, Kanarek R, Beinborn M (1999) The cholecystokinin-A receptor mediates inhibition of food intake yet is not essential for the maintenance of body weight. J Clin Invest 103(3):383–391. doi:10.​1172/​JCI4901 PubMedCentralPubMedCrossRef
130.
Koutcherov Y, Mai JK, Paxinos G (2003) Hypothalamus of the human fetus. J Chem Neuroanat 26(4):253–270PubMedCrossRef
131.
Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A (1998) Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 19(2):155–157. doi:10.​1038/​509 PubMedCrossRef
132.
Krude H, Biebermann H, Schnabel D, Tansek MZ, Theunissen P, Mullis PE, Gruters A (2003) Obesity due to proopiomelanocortin deficiency: three new cases and treatment trials with thyroid hormone and ACTH4-10. J Clin Endocrinol Metab 88(10):4633–4640PubMedCrossRef
133.
134.
135.
Laurenius A, Larsson I, Bueter M, Melanson KJ, Bosaeus I, Forslund HB, Lonroth H, Fandriks L, Olbers T (2012) Changes in eating behaviour and meal pattern following Roux-en-Y gastric bypass. Int J Obes 36(3):348–355. doi:10.​1038/​ijo.​2011.​217 CrossRef
136.
Laurenius A, Larsson I, Melanson KJ, Lindroos AK, Lonroth H, Bosaeus I, Olbers T (2013) Decreased energy density and changes in food selection following Roux-en-Y gastric bypass. Eur J Clin Nutr 67(2):168–173. doi:10.​1038/​ejcn.​2012.​208 PubMedCrossRef
137.
138.
Lee EB, Ahima RS (2011) Central regulation of appetite and satiety behavior. In: Preedy VR, Marin CR, Watson RR (eds) Handbook of behavior, food and nutrition. Springer, New York, pp 1023–1034CrossRef
139.
140.
Lee J, Duan W, Mattson MP (2002) Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J Neurochem 82(6):1367–1375PubMedCrossRef
141.
142.
143.
144.
145.
Licinio J, Caglayan S, Ozata M, Yildiz BO, de Miranda PB, O’Kirwan F, Whitby R, Liang L, Cohen P, Bhasin S, Krauss RM, Veldhuis JD, Wagner AJ, DePaoli AM, McCann SM, Wong ML (2004) Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc Natl Acad Sci USA 101(13):4531–4536. doi:10.​1073/​pnas.​0308767101 PubMedCrossRef
146.
Liel Y, Ulmer E, Shary J, Hollis BW, Bell NH (1988) Low circulating vitamin D in obesity. Calcif Tissue Int 43(4):199–201PubMedCrossRef
147.
Livingstone MB, Black AE (2003) Markers of the validity of reported energy intake. J Nutr 133(Suppl 3):895S–920SPubMed
148.
Luiten PG, ter Horst GJ, Steffens AB (1987) The hypothalamus, intrinsic connections and outflow pathways to the endocrine system in relation to the control of feeding and metabolism. Prog Neurobiol 28(1):1–54PubMedCrossRef
149.
150.
151.
152.
Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S et al (1995) Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1(11):1155–1161PubMedCrossRef
153.
Malek-Ahmadi M, Beach T, Obradov A, Sue L, Belden C, Davis K, Walker DG, Lue L, Adem A, Sabbagh MN (2013) Type 2 diabetes is associated with increased Alzheimer’s disease neuropathology in ApoE epsilon4 carriers. Curr Alzheimer Res 10(6):654–659
154.
Mark RJ, Pang Z, Geddes JW, Uchida K, Mattson MP (1997) Amyloid beta-peptide impairs glucose transport in hippocampal and cortical neurons: involvement of membrane lipid peroxidation. J Neurosci 17(3):1046–1054PubMed
155.
156.
157.
Matarese G, Carrieri PB, La Cava A, Perna F, Sanna V, De Rosa V, Aufiero D, Fontana S, Zappacosta S (2005) Leptin increase in multiple sclerosis associates with reduced number of CD4(+)CD25+ regulatory T cells. Proc Natl Acad Sci USA 102(14):5150–5155. doi:10.​1073/​pnas.​0408995102 PubMedCrossRef
158.
159.
Matarese G, Di Giacomo A, Sanna V, Lord GM, Howard JK, Di Tuoro A, Bloom SR, Lechler RI, Zappacosta S, Fontana S (2001) Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J Immunol 166(10):5909–5916PubMed
160.
Matochik JA, London ED, Yildiz BO, Ozata M, Caglayan S, DePaoli AM, Wong ML, Licinio J (2005) Effect of leptin replacement on brain structure in genetically leptin-deficient adults. J Clin Endocrinol Metab 90(5):2851–2854. doi:10.​1210/​jc.​2004-1979 PubMedCrossRef
161.
Matsuzaki T, Sasaki K, Tanizaki Y, Hata J, Fujimi K, Matsui Y, Sekita A, Suzuki SO, Kanba S, Kiyohara Y, Iwaki T (2010) Insulin resistance is associated with the pathology of Alzheimer disease: the Hisayama study. Neurology 75(9):764–770. doi:10.​1212/​WNL.​0b013e3181eee25f​ PubMedCrossRef
162.
163.
164.
165.
McAllister CJ, Whittington JE, Holland AJ (2011) Development of the eating behaviour in Prader–Willi syndrome: advances in our understanding. Int J Obes 35(2):188–197. doi:10.​1038/​ijo.​2010.​139 CrossRef
166.
167.
168.
Melka MG, Gillis J, Bernard M, Abrahamowicz M, Chakravarty MM, Leonard GT, Perron M, Richer L, Veillette S, Banaschewski T, Barker GJ, Buchel C, Conrod P, Flor H, Heinz A, Garavan H, Bruhl R, Mann K, Artiges E, Lourdusamy A, Lathrop M, Loth E, Schwartz Y, Frouin V, Rietschel M, Smolka MN, Strohle A, Gallinat J, Struve M, Lattka E, Waldenberger M, Schumann G, Pavlidis P, Gaudet D, Paus T, Pausova Z (2013) FTO, obesity and the adolescent brain. Hum Mol Genet 22(5):1050–1058. doi:10.​1093/​hmg/​dds504 PubMedCrossRef
169.
Michaud JL, Boucher F, Melnyk A, Gauthier F, Goshu E, Levy E, Mitchell GA, Himms-Hagen J, Fan CM (2001) Sim1 haploinsufficiency causes hyperphagia, obesity and reduction of the paraventricular nucleus of the hypothalamus. Hum Mol Genet 10(14):1465–1473PubMedCrossRef
170.
Michaud JL, Rosenquist T, May NR, Fan CM (1998) Development of neuroendocrine lineages requires the bHLH-PAS transcription factor SIM1. Genes Dev 12(20):3264–3275PubMedCrossRef
171.
Mohr B (1993) Neuropathology communication from Dr. Mohr, privat docent in Wurzburg. 1840. Obes Res 1(4):334–335PubMedCrossRef
172.
Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohammed SN, Hurst JA, Cheetham CH, Earley AR, Barnett AH, Prins JB, O’Rahilly S (1997) Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387(6636):903–908. doi:10.​1038/​43185 PubMedCrossRef
173.
174.
175.
176.
177.
178.
Munger KL, Zhang SM, O’Reilly E, Hernan MA, Olek MJ, Willett WC, Ascherio A (2004) Vitamin D intake and incidence of multiple sclerosis. Neurology 62(1):60–65PubMedCrossRef
179.
Nakagawa T, Tsuchida A, Itakura Y, Nonomura T, Ono M, Hirota F, Inoue T, Nakayama C, Taiji M, Noguchi H (2000) Brain-derived neurotrophic factor regulates glucose metabolism by modulating energy balance in diabetic mice. Diabetes 49(3):436–444PubMedCrossRef
180.
Nashold FE, Hoag KA, Goverman J, Hayes CE (2001) Rag-1-dependent cells are necessary for 1,25-dihydroxyvitamin D(3) prevention of experimental autoimmune encephalomyelitis. J Neuroimmunol 119(1):16–29PubMedCrossRef
181.
Nashold FE, Miller DJ, Hayes CE (2000) 1,25-dihydroxyvitamin D3 treatment decreases macrophage accumulation in the CNS of mice with experimental autoimmune encephalomyelitis. J Neuroimmunol 103(2):171–179PubMedCrossRef
182.
Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, Whitney A, Cross JH (2008) The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol 7(6):500–506. doi:10.​1016/​S1474-4422(08)70092-9 PubMedCrossRef
183.
184.
Norgan NG (2005) Laboratory and field measurements of body composition. Public Health Nutr 8 (7A):1108-1122
185.
Nourhashemi F, Deschamps V, Larrieu S, Letenneur L, Dartigues JF, Barberger-Gateau P (2003) Body mass index and incidence of dementia: the PAQUID study. Neurology 60(1):117–119PubMedCrossRef
186.
187.
188.
189.
Obeid M, Frank J, Medina M, Finckbone V, Bliss R, Bista B, Majmudar S, Hurst D, Strahlendorf H, Strahlendorf J (2010) Neuroprotective effects of leptin following kainic acid-induced status epilepticus. Epilepsy Behav. doi:10.​1016/​j.​yebeh.​2010.​07.​023 PubMed
190.
Organization WH (2013) Obesity and overweight. Fact Sheet 311
191.
Ozata M, Ozdemir IC, Licinio J (1999) Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J Clin Endocrinol Metab 84(10):3686–3695PubMedCrossRef
192.
Pan L, Blanck HM, Sherry B, Dalenius K, Grummer-Strawn LM (2012) Trends in the prevalence of extreme obesity among US preschool-aged children living in low-income families, 1998–2010. JAMA 308(24):2563–2565. doi:10.​1001/​jama.​2012.​108099 PubMedCrossRef
193.
194.
195.
Pedersen LB, Nashold FE, Spach KM, Hayes CE (2007) 1,25-Dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by inhibiting chemokine synthesis and monocyte trafficking. J Neurosci Res 85(11):2480–2490. doi:10.​1002/​jnr.​21382 PubMedCrossRef
196.
Pedersen WA, Chan SL, Mattson MP (2000) A mechanism for the neuroprotective effect of apolipoprotein E: isoform-specific modification by the lipid peroxidation product 4-hydroxynonenal. J Neurochem 74(4):1426–1433PubMedCrossRef
197.
Peila R, Rodriguez BL, Launer LJ (2002) Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: the Honolulu–Asia Aging Study. Diabetes 51(4):1256–1262PubMedCrossRef
198.
Pericak-Vance MA, Bebout JL, Gaskell PC Jr, Yamaoka LH, Hung WY, Alberts MJ, Walker AP, Bartlett RJ, Haynes CA, Welsh KA et al (1991) Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. Am J Hum Genet 48(6):1034–1050PubMedCentralPubMed
199.
200.
Pinkney J, Wilding J, Williams G, MacFarlane I (2002) Hypothalamic obesity in humans: what do we know and what can be done? Obes Rev 3(1):27–34PubMedCrossRef
201.
Principles and Practice of Endocrinology and Metabolism (2001). 3rd edn. Lippincott Williams & Wilkins, Philadelphia
202.
203.
Rahmouni K, Fath MA, Seo S, Thedens DR, Berry CJ, Weiss R, Nishimura DY, Sheffield VC (2008) Leptin resistance contributes to obesity and hypertension in mouse models of Bardet–Biedl syndrome. J Clin Invest 118(4):1458–1467. doi:10.​1172/​JCI32357 PubMedCentralPubMedCrossRef
204.
205.
Rauchenzauner M, Laimer M, Luef G, Kaser S, Engl J, Tatarczyk T, Ciardi C, Tschoner A, Lechleitner M, Patsch J, Ebenbichler CF (2008) Adiponectin receptor R1 is upregulated by valproic acid but not by topiramate in human hepatoma cell line, HepG2. Seizure 17(8):723–726. doi:10.​1016/​j.​seizure.​2008.​03.​002 PubMedCrossRef
206.
207.
208.
Regard M, Landis T (1997) “Gourmand syndrome”: eating passion associated with right anterior lesions. Neurology 48(5):1185–1190PubMedCrossRef
209.
Reinehr T, de Sousa G, Alexy U, Kersting M, Andler W (2007) Vitamin D status and parathyroid hormone in obese children before and after weight loss. Eur J Endocrinol 157(2):225–232. doi:10.​1530/​EJE-07-0188 PubMedCrossRef
210.
211.
212.
213.
Sachs GS, Guille C (1999) Weight gain associated with use of psychotropic medications. J Clin Psychiatry 60(Suppl 21):16–19PubMed
214.
Sagare AP, Bell RD, Srivastava A, Sengillo JD, Singh I, Nishida Y, Chow N, Zlokovic BV (2013) A lipoprotein receptor cluster IV mutant preferentially binds amyloid-beta and regulates its clearance from the mouse brain. J Biol Chem. doi:10.​1074/​jbc.​M112.​439570 PubMed
215.
Sander JW, Hart YM, Johnson AL, Shorvon SD (1990) National General Practice Study of Epilepsy: newly diagnosed epileptic seizures in a general population. Lancet 336(8726):1267–1271PubMedCrossRef
216.
Sander JW, Shorvon SD (1996) Epidemiology of the epilepsies. J Neurol Neurosurg Psychiatry 61(5):433–443PubMedCrossRef
217.
218.
219.
Seo S, Guo DF, Bugge K, Morgan DA, Rahmouni K, Sheffield VC (2009) Requirement of Bardet–Biedl syndrome proteins for leptin receptor signaling. Hum Mol Genet 18(7):1323–1331. doi:10.​1093/​hmg/​ddp031 PubMedCrossRef
220.
Shanley LJ, O’Malley D, Irving AJ, Ashford ML, Harvey J (2002) Leptin inhibits epileptiform-like activity in rat hippocampal neurones via PI 3-kinase-driven activation of BK channels. J Physiol 545(Pt 3):933–944. doi:PHY_​029488 PubMedCrossRef
221.
222.
223.
224.
225.
Soliman AT, Rajab A, AlSalmi I, Asfour MG (1996) Empty sellae, impaired testosterone secretion, and defective hypothalamic-pituitary growth and gonadal axes in children with Bardet–Biedl syndrome. Metabolism 45(10):1230–1234PubMedCrossRef
226.
Spach KM, Hayes CE (2005) Vitamin D3 confers protection from autoimmune encephalomyelitis only in female mice. J Immunol 175(6):4119–4126PubMed
227.
Spach KM, Nashold FE, Dittel BN, Hayes CE (2006) IL-10 signaling is essential for 1,25-dihydroxyvitamin D3-mediated inhibition of experimental autoimmune encephalomyelitis. J Immunol 177(9):6030–6037PubMed
228.
Spach KM, Pedersen LB, Nashold FE, Kayo T, Yandell BS, Prolla TA, Hayes CE (2004) Gene expression analysis suggests that 1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by stimulating inflammatory cell apoptosis. Physiol Genomics 18(2):141–151. doi:10.​1152/​physiolgenomics.​00003.​2004 PubMedCrossRef
229.
Spanier JA, Nashold FE, Olson JK, Hayes CE (2012) The Ifng gene is essential for Vdr gene expression and vitamin D(3)-mediated reduction of the pathogenic T cell burden in the central nervous system in experimental autoimmune encephalomyelitis, a multiple sclerosis model. J Immunol 189(6):3188–3197. doi:10.​4049/​jimmunol.​1102925 PubMedCrossRef
230.
231.
Sriram K, Benkovic SA, Miller DB, O’Callaghan JP (2002) Obesity exacerbates chemically induced neurodegeneration. Neuroscience 115(4):1335–1346PubMedCrossRef
232.
Stewart R, Masaki K, Xue QL, Peila R, Petrovitch H, White LR, Launer LJ (2005) A 32-year prospective study of change in body weight and incident dementia: the Honolulu–Asia Aging Study. Arch Neurol 62(1):55–60. doi:10.​1001/​archneur.​62.​1.​55 PubMedCrossRef
233.
234.
Stranahan AM, Lee K, Martin B, Maudsley S, Golden E, Cutler RG, Mattson MP (2009) Voluntary exercise and caloric restriction enhance hippocampal dendritic spine density and BDNF levels in diabetic mice. Hippocampus 19(10):951–961. doi:10.​1002/​hipo.​20577 PubMedCentralPubMedCrossRef
235.
Stranahan AM, Mattson MP (2012) Recruiting adaptive cellular stress responses for successful brain ageing. Nat Rev Neurosci 13(3):209–216
236.
Stricker EM (1984) Biological bases of hunger and satiety: therapeutic implications. Nutr Rev 42(10):333–340PubMedCrossRef
237.
Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD (1993) Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 90(5):1977–1981PubMedCrossRef
238.
239.
Stutzmann F, Ghoussaini M, Couturier C, Marchand M, Vatin V, Corset L, Lecoeur C, Balkau B, Horber F, Driscoll DJ, Goldstone AP, Weill J, Michaud JL, Meyre D, Froguel P (2009) Loss-of-function mutations in SIM1 cause a specific form of Prader–Willi-like syndrome. In: Diabetologia, vol 52. pp S104–S104
240.
Sun H, Huang Y, Yu X, Li Y, Yang J, Li R, Deng Y, Zhao G (2008) Peroxisome proliferator-activated receptor gamma agonist, rosiglitazone, suppresses CD40 expression and attenuates inflammatory responses after lithium pilocarpine-induced status epilepticus in rats. Int J Dev Neurosci 26(5):505–515. doi:10.​1016/​j.​ijdevneu.​2008.​01.​009 PubMedCrossRef
241.
Swaab DF (1997) Prader–Willi syndrome and the hypothalamus. Acta Paediatr Suppl 423:50–54PubMedCrossRef
242.
Swaab DF, Purba JS, Hofman MA (1995) Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader–Willi syndrome: a study of five cases. J Clin Endocrinol Metab 80(2):573–579PubMedCrossRef
243.
Swanson LW, Sawchenko PE, Wiegand SJ, Price JL (1980) Separate neurons in the paraventricular nucleus project to the median eminence and to the medulla or spinal cord. Brain Res 198(1):190–195PubMedCrossRef
244.
245.
Szabo AN, McAuley E, Erickson KI, Voss M, Prakash RS, Mailey EL, Wojcicki TR, White SM, Gothe N, Olson EA, Kramer AF (2011) Cardiorespiratory fitness, hippocampal volume, and frequency of forgetting in older adults. Neuropsychology 25(5):545–553. doi:10.​1037/​a0022733 PubMedCentralPubMedCrossRef
246.
Temkin O (1945) The falling sickness: a history of epilepsy from the Greeks to the beginnings of modern neurology, 2nd edn. Johns Hopkins Univ. Press, Baltimore
247.
Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR, Nguyen HT, Fischer JD, Matsen ME, Wisse BE, Morton GJ, Horvath TL, Baskin DG, Tschop MH, Schwartz MW (2012) Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest 122(1):153–162. doi:10.​1172/​JCI59660 PubMedCentralPubMedCrossRef
248.
249.
Ungerstedt U (1971) Stereotaxic mapping of the monoamine pathways in the rat brain. Acta Physiol Scand Suppl 367:1–48PubMed
250.
Vaisse C, Clement K, Guy-Grand B, Froguel P (1998) A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat Genet 20(2):113–114. doi:10.​1038/​2407 PubMedCrossRef
251.
van de Sande-Lee S, Pereira FR, Cintra DE, Fernandes PT, Cardoso AR, Garlipp CR, Chaim EA, Pareja JC, Geloneze B, Li LM, Cendes F, Velloso LA (2011) Partial reversibility of hypothalamic dysfunction and changes in brain activity after body mass reduction in obese subjects. Diabetes 60(6):1699–1704. doi:10.​2337/​db10-1614 PubMedCrossRef
252.
van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ (2009) Cold-activated brown adipose tissue in healthy men. N Engl J Med 360(15):1500–1508. doi:10.​1056/​NEJMoa0808718 PubMedCrossRef
253.
254.
Verghese PB, Castellano JM, Garai K, Wang Y, Jiang H, Shah A, Bu G, Frieden C, Holtzman DM (2013) ApoE influences amyloid-beta (Abeta) clearance despite minimal apoE/Abeta association in physiological conditions. Proc Natl Acad Sci USA 110(19):E1807–E1816. doi:10.​1073/​pnas.​1220484110 PubMedCrossRef
255.
256.
257.
Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerback S, Nuutila P (2009) Functional brown adipose tissue in healthy adults. N Engl J Med 360(15):1518–1525. doi:10.​1056/​NEJMoa0808949 PubMedCrossRef
258.
259.
Wansink B, Chandon P (2006) Meal size, not body size, explains errors in estimating the calorie content of meals. Ann Intern Med 145(5):326–332PubMedCrossRef
260.
261.
262.
263.
Willette AA, Bendlin BB, Colman RJ, Kastman EK, Field AS, Alexander AL, Sridharan A, Allison DB, Anderson R, Voytko ML, Kemnitz JW, Weindruch RH, Johnson SC (2012) Calorie restriction reduces the influence of glucoregulatory dysfunction on regional brain volume in aged rhesus monkeys. Diabetes 61(5):1036–1042. doi:10.​2337/​db11-1187 PubMedCrossRef
264.
Willette AA, Xu G, Johnson SC, Birdsill AC, Jonaitis EM, Sager MA, Hermann BP, La Rue A, Asthana S, Bendlin BB (2013) Insulin resistance, brain atrophy, and cognitive performance in late middle-aged adults. Diabetes Care 36(2):443–449. doi:10.​2337/​dc12-0922 PubMedCrossRef
265.
266.
267.
Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF (2000) Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 72(3):690–693PubMed
268.
Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR, Tecott LH, Reichardt LF (2003) Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci 6(7):736–742. doi:10.​1038/​nn1073 PubMedCentralPubMedCrossRef
269.
Xu L, Rensing N, Yang XF, Zhang HX, Thio LL, Rothman SM, Weisenfeld AE, Wong M, Yamada KA (2008) Leptin inhibits 4-aminopyridine- and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in rodents. J Clin Invest 118(1):272–280. doi:10.​1172/​JCI33009 PubMedCentralPubMedCrossRef
270.
Yarchoan M, Xie SX, Kling MA, Toledo JB, Wolk DA, Lee EB, Van Deerlin V, Lee VM, Trojanowski JQ, Arnold SE (2012) Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias. Brain 135(Pt 12):3749–3756. doi:10.​1093/​brain/​aws271 PubMedCrossRef
271.
Yeo GS, Connie Hung CC, Rochford J, Keogh J, Gray J, Sivaramakrishnan S, O’Rahilly S, Farooqi IS (2004) A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat Neurosci 7(11):1187–1189. doi:10.​1038/​nn1336 PubMedCrossRef
272.
Yeo GS, Farooqi IS, Aminian S, Halsall DJ, Stanhope RG, O’Rahilly S (1998) A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet 20(2):111–112. doi:10.​1038/​2404 PubMedCrossRef
273.
Yu X, Shao XG, Sun H, Li YN, Yang J, Deng YC, Huang YG (2008) Activation of cerebral peroxisome proliferator-activated receptors gamma exerts neuroprotection by inhibiting oxidative stress following pilocarpine-induced status epilepticus. Brain Res 1200:146–158. doi:10.​1016/​j.​brainres.​2008.​01.​047 PubMedCrossRef
274.
Yura S, Itoh H, Sagawa N, Yamamoto H, Masuzaki H, Nakao K, Kawamura M, Takemura M, Kakui K, Ogawa Y, Fujii S (2005) Role of premature leptin surge in obesity resulting from intrauterine undernutrition. Cell Metab 1(6):371–378. doi:10.​1016/​j.​cmet.​2005.​05.​005 PubMedCrossRef
275.
276.
Metadaten
Titel
The neuropathology of obesity: insights from human disease
verfasst von
Edward B. Lee
Mark P. Mattson
Publikationsdatum
01.01.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Acta Neuropathologica / Ausgabe 1/2014
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-013-1190-x

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