Genes and the hypothalamic control of metabolism in humans

Best Practice and Research: Clinical Endocrinology and Metabolism

Volumn 28, Issue 5, 2014, Pages 635-647

  Hinney, Anke ^a   Volckmar, Anna Lena ^a   Antel, Jochen ^a  

^a UNIVERSITY HOSPITAL ESSEN   (Germany)

Author keywords

heritability; major gene; monogenic; obesity; polygenic variants

Indexed keywords

BODY WEIGHT; GENE MUTATION; GENETIC ANALYSIS; HERITABILITY; HUMAN; HYPOTHALAMUS; METABOLIC REGULATION; MULTIFACTORIAL INHERITANCE; OBESITY; PHENOTYPE; REVIEW; WEIGHT CONTROL; ENERGY METABOLISM; GENETIC PREDISPOSITION; GENETIC VARIABILITY; GENETICS; METABOLISM;

BODY WEIGHT; ENERGY METABOLISM; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; HUMANS; HYPOTHALAMUS; OBESITY; PHENOTYPE;

EID: 84924034918     PISSN: 1521690X     EISSN: 15321908     Source Type: Journal    
DOI: 10.1016/j.beem.2014.04.007     Document Type: Review

References (144)

1. J. Hebebrand, A. Scherag, and B.G. Schimmelmann Child and adolescent psychiatric genetics Eur Child Adolesc Psychiatry 19 2010 259 279
2. C.M. Brooks The history of thought concerning the hypothalamus and its functions Brain Res Bull 20 1988 657 667
3. L. Rinaman Visceral sensory inputs to the endocrine hypothalamus Front Neuroendocrinol 28 2007 50 60
4. D.A. Denton, M.J. McKinley, and R.S. Weisinger Hypothalamic integration of body fluid regulation Proc Natl Acad Sci U S A 93 1996 7397 7404
5. A. Rolls Hypothalamic control of sleep in aging Neuromol Med 14 2012 139 153
6. J.T. George, and S.B. Seminara Kisspeptin and the hypothalamic control of reproduction: lessons from the human Endocrinology 153 2012 5130 5136
7. I. Antal-Zimanyi, and X. Khawaja The role of melanin-concentrating hormone in energy homeostasis and mood disorders J Mol Neurosci 39 2009 86 98
8. F. Xiong, and L. Zhang Role of the hypothalamic-pituitary-adrenal axis in developmental programming of health and disease Front Neuroendocrinol 34 2013 27 46
9. N.R. Lenard, and H.R. Berthoud Central and peripheral regulation of food intake and physical activity: pathways and genes Obesity 16 Suppl. 3 2008 S11 S22
10. H.R. Berthoud, and H. Munzberg The lateral hypothalamus as integrator of metabolic and environmental needs: from electrical self-stimulation to opto-genetics Physiol Behav 104 2011 29 39
11. B.K. Anand, and J.R. Brobeck Localization of a "feeding center" in the hypothalamus of the rat Proc Soc Exp Biol Med Soc Exp Biol Med 77 1951 323 324
12. J.R. Brobeck Mechanism of the development of obesity in animals with hypothalamic lesions Physiol Rev 26 1946 541 559
13. B.M. King The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight Physiol Behav 87 2006 221 244
14. L.W. Swanson, G. Sanchez-Watts, and A.G. Watts Comparison of melanin-concentrating hormone and hypocretin/orexin mRNA expression patterns in a new parceling scheme of the lateral hypothalamic zone Neurosci Lett 387 2005 80 84
15. K.W. Williams, and J.K. Elmquist Lighting up the hypothalamus: coordinated control of feeding behavior Nat Neurosci 14 2011 277 278
16. H.R. Berthoud, H. Munzberg, and B.K. Richards Neural and metabolic regulation of macronutrient intake and selection Proc Nutr Soc 71 2012 390 400
17. H. Zheng, N.R. Lenard, and A.C. Shin Appetite control and energy balance regulation in the modern world: reward-driven brain overrides repletion signals Int J Obes 33 Suppl. 2 2009 S8 S13
18. J.E. Wikberg, and F. Mutulis Targeting melanocortin receptors: an approach to treat weight disorders and sexual dysfunction Nat Rev Drug Discov 7 2008 307 323
19. M.G. Myers Jr., and D.P. Olson Central nervous system control of metabolism Nature 491 2012 357 363
20. A. Hinney, A.L. Volckmar, and N. Knoll Melanocortin-4 receptor in energy homeostasis and obesity pathogenesis Prog Mol Biol Transl Sci 114 2013 147 191
21. B. Xu, E.H. Goulding, and K. Zang Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor Nat Neurosci 6 2003 736 742
22. H.R. Berthoud, and C. Morrison The brain, appetite, and obesity Annu Rev Psychol 59 2008 55 92
23. H.R. Berthoud Metabolic and hedonic drives in the neural control of appetite: who is the boss? Curr Opin Neurobiol 21 2011 888 896
24. E. Egecioglu, K.P. Skibicka, and C. Hansson Hedonic and incentive signals for body weight control Rev Endocr Metab Disord 12 2011 141 151
25. G.J. Wang, N.D. Volkow, and J.S. Fowler The role of dopamine in motivation for food in humans: implications for obesity Expert Opin Ther Targets 6 2002 601 609
26. H.L. Fehm, W. Kern, and A. Peters The selfish brain: competition for energy resources Prog Brain Res 153 2006 129 140
27. E.J. Nunes, P.A. Randall, and S. Podurgiel Nucleus accumbens neurotransmission and effort-related choice behavior in food motivation: effects of drugs acting on dopamine, adenosine, and muscarinic acetylcholine receptors Neurosci Biobehav Rev 37 2013 2015 2025
28. F.J. Meye, and R.A. Adan Feelings about food: the ventral tegmental area in food reward and emotional eating Trends Pharmacol Sci 35 2014 31 40
29. K.C. Berridge, C.Y. Ho, and J.M. Richard The tempted brain eats: pleasure and desire circuits in obesity and eating disorders Brain Res 1350 2010 43 64
30. M.L. Kringelbach Food for thought: hedonic experience beyond homeostasis in the human brain Neuroscience 126 2004 807 819
31. N. Weltens, D. Zhao, and L. Van Oudenhove Where is the comfort in comfort foods? Mechanisms linking fat signaling, reward, and emotion Neurogastroenterol Motil - Off J Eur Gastrointest Motil Soc 26 2014 303 315
32. G.D. Petrovich, and M. Gallagher Control of food consumption by learned cues: a forebrain-hypothalamic network Physiol Behav 91 2007 397 403
33. K.C. Berridge 'Liking' and 'wanting' food rewards: brain substrates and roles in eating disorders Physiol Behav 97 2009 537 550
34. D.M. Opland, G.M. Leinninger, and M.G. Myers Jr. Modulation of the mesolimbic dopamine system by leptin Brain Res 1350 2010 65 70
35. R. van Zessen, G. van der Plasse, and R.A. Adan Contribution of the mesolimbic dopamine system in mediating the effects of leptin and ghrelin on feeding Proc Nutr Soc 71 2012 435 445
36. S.H. Lockie, and Z.B. Andrews The hormonal signature of energy deficit: increasing the value of food reward Mol Metab 2 2013 329 336
37. M.A. Cornier, K.L. McFadden, and E.A. Thomas Differences in the neuronal response to food in obesity-resistant as compared to obesity-prone individuals Physiol Behav 110-111 2013 122 128
38. O. Albayrak, S.M. Wolfle, and J. Hebebrand Does food addiction exist? A phenomenological discussion based on the psychiatric classification of substance-related disorders and addiction Obes Facts 5 2012 165 179
39. P. Sumithran, L.A. Prendergast, and E. Delbridge Long-term persistence of hormonal adaptations to weight loss N Engl J Med 365 2011 1597 1604
40. C.T. Montague, I.S. Farooqi, and J.P. Whitehead Congenital leptin deficiency is associated with severe early-onset obesity in humans Nature 387 1997 903 908
41. K. Clement, C. Vaisse, and N. Lahlou A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction Nature 392 1998 398 401
42. A. Hinney, T. Bettecken, and P. Tarnow Prevalence, spectrum, and functional characterization of melanocortin-4 receptor gene mutations in a representative population-based sample and obese adults from Germany J Clin Endocrinol Metab 91 2006 1761 1769
43. I.S. Farooqi, and S. O'Rahilly Monogenic obesity in humans Annu Rev Med 56 2005 443 458
44. I.S. Farooqi, and S. O'Rahilly Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity Nat Clin Pract Endocrinol Metabol 4 2008 569 577
45. H. Rosas-Vargas, J.D. Martinez-Ezquerro, and T. Bienvenu Brain-derived neurotrophic factor, food intake regulation, and obesity Arch Med Res 42 2011 482 494
46. G.S. Yeo, C.C. Connie Hung, and J. Rochford A de novo mutation affecting human TrkB associated with severe obesity and developmental delay Nat Neurosci 7 2004 1187 1189
47. J. Gray, G. Yeo, and C. Hung Functional characterization of human NTRK2 mutations identified in patients with severe early-onset obesity Int J Obes 31 2007 359 364
48. Y.S. Lee The role of leptin-melanocortin system and human weight regulation: lessons from experiments of nature Ann Acad Med Singap 38 2009 34-11
49. M.E. Doche, E.G. Bochukova, and H.W. Su Human SH2B1 mutations are associated with maladaptive behaviors and obesity J Clin Invest 122 2012 4732 4736
50. A.L. Volckmar, C. Putter, and J.Y. Song Analyses of non-synonymous obesity risk alleles in SH2B1 (rs7498665) and APOB48R (rs180743) in obese children and adolescents undergoing a 1-year lifestyle intervention Exp Clin Endocrinol Diabetes - Off J Ger Soc Endocrinol, Ger Diabetes Assoc 121 2013 334 337
51. A.D. Borman, L.R. Pearce, and D.S. Mackay A homozygous mutation in the TUB gene associated with retinal dystrophy and obesity Hum Mutat 35 2014 289 293
52. A. Strobel, T. Issad, and L. Camoin A leptin missense mutation associated with hypogonadism and morbid obesity Nat Genet 18 1998 213 215
53. M.K. Karvonen, U. Pesonen, and P. Heinonen Identification of new sequence variants in the leptin gene J Clin Endocrinol Metab 83 1998 3239 3242
54. I.S. Farooqi, S.A. Jebb, and G. Langmack Effects of recombinant leptin therapy in a child with congenital leptin deficiency N Engl J Med 341 1999 879 884
55. G. Paz-Filho, K. Esposito, and B. Hurwitz Changes in insulin sensitivity during leptin replacement therapy in leptin-deficient patients Am J Physiol Endocrinol Metab 295 2008 E1401 E1408
56. I. Mazen, M. El-Gammal, and M. Abdel-Hamid A novel homozygous missense mutation of the leptin gene (N103K) in an obese Egyptian patient Mol Genet Metabol 97 2009 305 308
57. S. Saeed, T.A. Butt, and M. Anwer High prevalence of leptin and melanocortin-4 receptor gene mutations in children with severe obesity from Pakistani consanguineous families Mol Genet Metabol 106 2012 121 126
58. B. Dubern, and K. Clement Leptin and leptin receptor-related monogenic obesity Biochimie 94 2012 2111 2115
59. R.S. Jackson, J.W. Creemers, and S. Ohagi Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene Nat Genet 16 1997 303 306
60. R.S. Jackson, J.W. Creemers, and I.S. Farooqi Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency J Clin Invest 112 2003 1550 1560
61. H. Krude, H. Biebermann, and W. Luck Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans Nat Genet 19 1998 155 157
62. B.G. Challis, L.E. Pritchard, and J.W. Creemers 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 2002 1997 2004
63. E. Miraglia del Giudice, G. Cirillo, and N. Santoro Molecular screening of the proopiomelanocortin (POMC) gene in Italian obese children: report of three new mutations Int J Obes Relat Metabol Disord - J Int Assoc Study Obes 25 2001 61 67
64. M. Mencarelli, A. Zulian, and R. Cancello A novel missense mutation in the signal peptide of the human POMC gene: a possible additional link between early-onset type 2 diabetes and obesity Eur J Hum Genet 20 2012 1290 1294
65. H. Biebermann, P. Kuhnen, and G. Kleinau The neuroendocrine circuitry controlled by POMC, MSH, and AGRP Handb Exp Pharmacol 2012 47 75
66. T. Rankinen, A. Zuberi, and Y.C. Chagnon The human obesity gene map: the 2005 update Obesity 14 2006 529 644
67. I.S. Farooqi, and S. O'Rahilly New advances in the genetics of early onset obesity Int J Obes 29 2005 1149 1152
68. S. Farooqi, and S. O'Rahilly Genetics of obesity in humans Endocr Rev 27 2006 710 718
69. A. Hinney, C.I. Vogel, and J. Hebebrand From monogenic to polygenic obesity: recent advances Eur Child Adolesc Psychiatry 19 2010 297 310
70. W.T. Gibson, I.S. Farooqi, and M. Moreau Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapy J Clin Endocrinol Metab 89 2004 4821 4826
71. J. Licinio, S. Caglayan, and M. Ozata Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults Proc Natl Acad Sci U S A 101 2004 4531 4536
72. I.S. Farooqi, G. Matarese, and G.M. Lord Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency J Clin Invest 110 2002 1093 1103
73. I.S. Farooqi, E. Bullmore, and J. Keogh Leptin regulates striatal regions and human eating behavior Science 317 2007 1355
74. I.S. Farooqi, T. Wangensteen, and S. Collins Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor N Engl J Med 356 2007 237 247
75. I.S. Farooqi, and S. O'Rahilly Leptin: a pivotal regulator of human energy homeostasis Am J Clin Nutr 89 2009 980S 984S
76. D. Huszar, C.A. Lynch, and V. Fairchild-Huntress Targeted disruption of the melanocortin-4 receptor results in obesity in mice Cell 88 1997 131 141
77. G.S. Yeo, I.S. Farooqi, and S. Aminian A frameshift mutation in MC4R associated with dominantly inherited human obesity Nat Genet 20 1998 111 112
78. C. Vaisse, K. Clement, and B. Guy-Grand A frameshift mutation in human MC4R is associated with a dominant form of obesity Nat Genet 20 1998 113 114
79. A. Hinney, A. Schmidt, and K. Nottebom Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans J Clin Endocrinol Metab 84 1999 1483 1486
80. E. Rettenbacher, P. Tarnow, and H. Brumm A novel non-synonymous mutation in the melanocortin-4 receptor gene (MC4R) in a 2-year-old Austrian girl with extreme obesity Exp Clin Endocrinol Diabetes - Off J Ger Soc Endocrinol, Ger Diabetes Assoc 115 2007 7 12
81. A. Hinney, S. Hohmann, and F. Geller Melanocortin-4 receptor gene: case-control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesity J Clin Endocrinol Metab 88 2003 4258 4267
82. C. Vaisse, K. Clement, and E. Durand Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity J Clin Invest 106 2000 253 262
83. Y.X. Tao Molecular mechanisms of the neural melanocortin receptor dysfunction in severe early onset obesity Mol Cell Endocrinol 239 2005 1 14
84. Y.X. Tao, and D.L. Segaloff Functional characterization of melanocortin-4 receptor mutations associated with childhood obesity Endocrinology 144 2003 4544 4551
85. I.S. Farooqi, J.M. Keogh, and G.S. Yeo Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene N Engl J Med 348 2003 1085 1095
86. G. Cai, S.A. Cole, and N. Butte A quantitative trait locus on chromosome 18q for physical activity and dietary intake in Hispanic children Obesity 14 2006 1596 1604
87. I.S. Farooqi, G.S. Yeo, and S. O'Rahilly Binge eating as a phenotype of melanocortin 4 receptor gene mutations N Engl J Med 349 2003 606 609 [author reply-9]
88. J. Hebebrand, F. Geller, and A. Dempfle Binge-eating episodes are not characteristic of carriers of melanocortin-4 receptor gene mutations Mol Psychiatry 9 2004 796 800
89. N. Potoczna, R. Branson, and J.G. Kral Gene variants and binge eating as predictors of comorbidity and outcome of treatment in severe obesity J Gastrointest Surg - Off J Soc Surg Aliment Tract 8 2004 971 981 [discussion 81-2]
90. S. Herpertz, W. Siffert, and J. Hebebrand Binge eating as a phenotype of melanocortin 4 receptor gene mutations N Engl J Med 349 2003 606 609 [author reply-9]
91. A. Dempfle, A. Hinney, and M. Heinzel-Gutenbrunner Large quantitative effect of melanocortin-4 receptor gene mutations on body mass index J Med Genet 41 2004 795 800
92. A. Hinney, and J. Hebebrand Polygenic obesity in humans Obes Facts 1 2008 35 42
93. R.J. Loos, C.M. Lindgren, and S. Li Common variants near MC4R are associated with fat mass, weight and risk of obesity Nat Genet 40 2008 768 775
94. M. Hofker, and C. Wijmenga A supersized list of obesity genes Nat Genet 41 2009 139 140
95. C.J. Willer, E.K. Speliotes, and R.J. Loos Six new loci associated with body mass index highlight a neuronal influence on body weight regulation Nat Genet 41 2009 25 34
96. E.K. Speliotes, C.J. Willer, and S.I. Berndt Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index Nat Genet 42 2010 937 948
97. J.P. Bradfield, H.R. Taal, and N.J. Timpson A genome-wide association meta-analysis identifies new childhood obesity loci Nat Genet 44 2012 526 531
98. Y. Okada, M. Kubo, and H. Ohmiya Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations Nat Genet 44 2012 302 306
99. W. Wen, Y.S. Cho, and W. Zheng Meta-analysis identifies common variants associated with body mass index in east Asians Nat Genet 44 2012 307 311
100. S.I. Berndt, S. Gustafsson, and R. Magi Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture Nat Genet 45 2013 501 512
101. G. Thorleifsson, G.B. Walters, and D.F. Gudbjartsson Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity Nat Genet 41 2009 18 24
102. K.L. Monda, G.K. Chen, and K.C. Taylor A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry Nat Genet 45 2013 690 696
103. E. Wheeler, N. Huang, and E.G. Bochukova Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity Nat Genet 45 2013 513 517
104. R.G. Walters, S. Jacquemont, and A. Valsesia A new highly penetrant form of obesity due to deletions on chromosome 16p11.2 Nature 463 2010 671 675
105. F. Geller, K. Reichwald, and A. Dempfle Melanocortin-4 receptor gene variant I103 is negatively associated with obesity Am J Hum Genet 74 2004 572 581
106. F. Stutzmann, V. Vatin, and S. Cauchi Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: the two facets of a Janus obesity gene Hum Mol Genet 16 2007 1837 1844
107. I.M. Heid, C. Vollmert, and A. Hinney Association of the 103I MC4R allele with decreased body mass in 7937 participants of two population based surveys J Med Genet 42 2005 e21
108. E.H. Young, N.J. Wareham, and S. Farooqi The V103I polymorphism of the MC4R gene and obesity: population based studies and meta-analysis of 29 563 individuals Int J Obes 31 2007 1437 1441
109. D. Wang, J. Ma, and S. Zhang Association of the MC4R V103I polymorphism with obesity: a Chinese case-control study and meta-analysis in 55,195 individuals Obesity 18 2010 573 579
110. Z. Xiang, S.A. Litherland, and N.B. Sorensen Pharmacological characterization of 40 human melanocortin-4 receptor polymorphisms with the endogenous proopiomelanocortin-derived agonists and the agouti-related protein (AGRP) antagonist Biochemistry 45 2006 7277 7288
111. T.M. Frayling, N.J. Timpson, and M.N. Weedon A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity Science 316 2007 889 894
112. C.H. Sandholt, M.A. Vestmar, and D.S. Bille Studies of metabolic phenotypic correlates of 15 obesity associated gene variants PLoS One 6 2011 e23531
113. J. Hebebrand, A. Hinney, and N. Knoll Molecular genetic aspects of weight regulation Dtsch Arzteblatt Int 110 2013 338 344
114. C. Dina, D. Meyre, and S. Gallina Variation in FTO contributes to childhood obesity and severe adult obesity Nat Genet 39 2007 724 726
115. A. Scuteri, S. Sanna, and W.M. Chen Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits PLoS Genet 3 2007 e115
116. A. Hinney, T.T. Nguyen, and A. Scherag Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants PLoS One 2 2007 e1361
117. D. Meyre, K. Proulx, and H. Kawagoe-Takaki Prevalence of loss-of-function FTO mutations in lean and obese individuals Diabetes 59 2010 311 318
118. P. Rzehak, A. Scherag, and H. Grallert Associations between BMI and the FTO gene are age dependent: results from the GINI and LISA birth cohort studies up to age 6 years Obes Facts 3 2010 173 180
119. M. Hakanen, O.T. Raitakari, and T. Lehtimaki FTO genotype is associated with body mass index after the age of seven years but not with energy intake or leisure-time physical activity J Clin Endocrinol Metab 94 2009 1281 1287
120. J.R. Speakman, K.A. Rance, and A.M. Johnstone Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure Obesity 16 2008 1961 1965
121. J.E. Cecil, R. Tavendale, and P. Watt An obesity-associated FTO gene variant and increased energy intake in children N Engl J Med 359 2008 2558 2566
122. J. Wardle, S. Carnell, and C.M. Haworth Obesity associated genetic variation in FTO is associated with diminished satiety J Clin Endocrinol Metab 93 2008 3640 3643
123. S.L. Park, I. Cheng, and S.A. Pendergrass Association of the FTO obesity risk variant rs8050136 with percentage of energy intake from fat in multiple racial/ethnic populations: the PAGE study Am J Epidemiol 178 2013 780 790
124. A. Jonsson, F. Renstrom, and V. Lyssenko Assessing the effect of interaction between an FTO variant (rs9939609) and physical activity on obesity in 15,925 Swedish and 2,511 Finnish adults Diabetologia 52 2009 1334 1338
125. A.S. Richardson, K.E. North, and M. Graff Moderate to vigorous physical activity interactions with genetic variants and body mass index in a large US ethnically diverse cohort Pediatr Obes 9 2014 e35 e46
126. V. Ott, H. Oster, and H. Lehnert FTO-genotype affects postprandial neuronal responses to visual food cues Mol Metab 3 2014 84 85
127. M. Heni, S. Kullmann, and R. Veit Variation in the obesity risk gene FTO determines the postprandial cerebral processing of food stimuli in the prefrontal cortex Mol Metab 3 2014 109 113
128. T. Berulava, and B. Horsthemke The obesity-associated SNPs in intron 1 of the FTO gene affect primary transcript levels Eur J Hum Genet 18 2010 1054 1056
129. T. Gerken, C.A. Girard, and Y.C. Tung The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase Science 318 2007 1469 1472
130. L. Sanchez-Pulido, and M.A. Andrade-Navarro The FTO (fat mass and obesity associated) gene codes for a novel member of the non-heme dioxygenase superfamily BMC Biochem 8 2007 23
131. K. Wahlen, E. Sjolin, and J. Hoffstedt The common rs9939609 gene variant of the fat mass- and obesity-associated gene FTO is related to fat cell lipolysis J Lipid Res 49 2008 607 611
132. G. Jia, C.G. Yang, and S. Yang Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO FEBS Lett 582 2008 3313 3319
133. J. Fischer, L. Koch, and C. Emmerling Inactivation of the Fto gene protects from obesity Nature 458 2009 894 898
134. C. Church, S. Lee, and E.A. Bagg A mouse model for the metabolic effects of the human fat mass and obesity associated FTO gene PLoS Genet 5 2009 e1000599
135. C. Church, L. Moir, and F. McMurray Overexpression of Fto leads to increased food intake and results in obesity Nat Genet 42 2010 1086 1092
136. F. McMurray, C.D. Church, and R. Larder Adult onset global loss of the fto gene alters body composition and metabolism in the mouse PLoS Genet 9 2013 e1003166
137. E. Fisher, M.B. Schulze, and N. Stefan Association of the FTO rs9939609 single nucleotide polymorphism with C-reactive protein levels Obesity 17 2009 330 334
138. T.D. Muller, M.H. Tschop, and S. Hofmann Emerging function of fat mass and obesity-associated protein (fto) PLoS Genet 9 2013 e1003223
139. S. Smemo, J.J. Tena, and K.H. Kim Obesity-associated variants within FTO form long-range functional connections with IRX3 Nature 507 2014 371 375
140. S. Friedel, F.F. Horro, and A.K. Wermter Mutation screen of the brain derived neurotrophic factor gene (BDNF): identification of several genetic variants and association studies in patients with obesity, eating disorders, and attention-deficit/hyperactivity disorder Am J Med Genet Part B - Neuropsychiatr Genet Off Publ Int Soc Psychiatric Genet 132B 2005 96 99
141. J. Gray, G.S. Yeo, and J.J. Cox Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene Diabetes 55 2006 3366 3371
142. H. Jiao, P. Arner, and J. Hoffstedt Genome wide association study identifies KCNMA1 contributing to human obesity BMC Med Genomics 4 2011 51
143. Y.J. Liu, X.G. Liu, and L. Wang Genome-wide association scans identified CTNNBL1 as a novel gene for obesity Hum Mol Genet 17 2008 1803 1813
144. A. Scherag, I. Jarick, and J. Grothe Investigation of a genome wide association signal for obesity: synthetic association and haplotype analyses at the melanocortin 4 receptor gene locus PLoS One 5 2010 e13967