Genetics of obesity: can an old dog teach us new tricks?

Diabetologia

Volumn 60, Issue 5, 2017, Pages 778-783

  Yeo, Giles S H ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Appetite; Body weight; Food intake; Genetics; Hypothalamus; Melanocortin; Obesity; Review

Indexed keywords

LEPTIN; MELANOCORTIN; PROOPIOMELANOCORTIN;

APPETITE; BODY MASS; DISEASE SEVERITY; EPIGENETICS; FOOD INTAKE; GENETIC DISORDER; GENETICS; GENOME-WIDE ASSOCIATION STUDY; HOMEOSTASIS; HUMAN; NONHUMAN; OBESITY; PRIORITY JOURNAL; REVIEW; ANIMAL; DOG; EATING; HYPOTHALAMUS; METABOLISM;

ANIMALS; BODY MASS INDEX; DOGS; EATING; GENOME-WIDE ASSOCIATION STUDY; HUMANS; HYPOTHALAMUS; MELANOCORTINS; OBESITY;

EID: 85007174205     PISSN: 0012186X     EISSN: 14320428     Source Type: Journal    
DOI: 10.1007/s00125-016-4187-x     Document Type: Review

References (29)

1. Stunkard AJ, Foch TT, Hrubec Z (1986) A twin study of human obesity. JAMA 256:51–54
2. Stunkard AJ, Harris JR, Pedersen NL, McClearn GE (1990) The body-mass index of twins who have been reared apart. N Engl J Med 322:1483–1487
3. Yeo GS, Heisler LK (2012) Unraveling the brain regulation of appetite: lessons from genetics. Nat Neurosci 15:1343–1349
4. Cone RD (2005) Anatomy and regulation of the central melanocortin system. Nat Neurosci 8:571–578
5. 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 372:425–432
6. Montague CT, Farooqi IS, Whitehead JP et al (1997) Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387:903–908
7. Farooqi IS, Jebb SA, Langmack G et al (1999) Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 341:879–884
8. Heymsfield SB, Greenberg AS, Fujioka K et al (1999) Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 282:1568–1575
9. Ahima RS, Prabakaran D, Mantzoros C et al (1996) Role of leptin in the neuroendocrine response to fasting. Nature 382:250–252
10. Challis BG, Coll AP, Yeo GS et al (2004) Mice lacking pro-opiomelanocortin are sensitive to high-fat feeding but respond normally to the acute anorectic effects of peptide-YY(3-36). Proc Natl Acad Sci U S A 101:4695–4700
11. 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 19:155–157
12. Huszar D, Lynch CA, Fairchild-Huntress V et al (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88:131–141
13. 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 20:113–114
14. 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 20:111–112
15. Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O’Rahilly S (2003) Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 348:1085–1095
16. Alharbi KK, Spanakis E, Tan K et al (2007) Prevalence and functionality of paucimorphic and private MC4R mutations in a large, unselected European British population, scanned by meltMADGE. Hum Mutat 28:294–302
17. Challis BG, Pritchard LE, Creemers JW et al (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 11:1997–2004
18. Lee YS, Challis BG, Thompson DA et al (2006) A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balance. Cell Metab 3:135–140
19. Raffan E, Dennis RJ, O’Donovan CJ et al (2016) A deletion in the canine POMC gene is associated with weight and appetite in obesity-prone labrador retriever dogs. Cell Metab 23:893–900
20. Sutter NB, Ostrander EA (2004) Dog star rising: the canine genetic system. Nat Rev Genet 5:900–910
21. Raffan E, Smith SP, O’Rahilly S, Wardle J (2015) Development, factor structure and application of the Dog Obesity Risk and Appetite (DORA) questionnaire. PeerJ 3, e1278
22. Kühnen P, Mischke M, Wiegand S et al (2012) An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity. PLoS Genet 8, e1002543
23. Kühnen P, Handke D, Waterland RA et al (2016) Interindividual variation in DNA methylation at a putative POMC metastable epiallele is associated with obesity. Cell Metab 24:502–509
24. Kühnen P, Clement K, Wiegand S et al (2016) Proopiomelanocortin deficiency treated with a melanocortin-4 receptor agonist. N Engl J Med 375:240–246
25. Greenfield JR, Miller JW, Keogh JM et al (2009) Modulation of blood pressure by central melanocortinergic pathways. N Engl J Med 360:44–52
26. Frayling TM, Timpson NJ, Weedon MN et al (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889–894
27. Loos RJ (2012) Genetic determinants of common obesity and their value in prediction. Best Pract Res Clin Endocrinol Metab 26:211–226
28. Shungin D, Winkler TW, Croteau-Chonka DC et al (2015) New genetic loci link adipose and insulin biology to body fat distribution. Nature 518:187–196
29. Locke AE, Kahali B, Berndt SI et al (2015) Genetic studies of body mass index yield new insights for obesity biology. Nature 518:197–206