Adult Onset Global Loss of the Fto Gene Alters Body Composition and Metabolism in the Mouse

PLoS Genetics

Volumn 9, Issue 1, 2013, Pages

  McMurray, Fiona ^a   Church, Chris D ^a   Larder, Rachel ^b   Nicholson, George ^a,c   Wells, Sara ^a   Teboul, Lydia ^a   Tung, Y C Loraine ^b   Rimmington, Debra ^b   Bosch, Fatima ^d,e   Jimenez, Veronica ^d,e   Yeo, Giles S H ^b   O'Rahilly, Stephen ^b   Ashcroft, Frances M ^f   Coll, Anthony P ^b   Cox, Roger D ^a  

^a MRC Harwell   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^e INSTITUTO DE SALUD CARLOS III   (Spain)

^f UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CRE RECOMBINASE; PARVOVIRUS VECTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY COMPOSITION; BODY HEIGHT; CONTROLLED STUDY; ENERGY EXPENDITURE; ENERGY METABOLISM; FAT MASS; FEMALE; FOOD INTAKE; FTO GENE; GENE; GENE DELETION; GENE EXPRESSION; GENE LOSS; GERM LINE; LEAN BODY WEIGHT; MALE; MEDIOBASAL HYPOTHALAMUS; MOUSE; NONHUMAN; PERINATAL DEATH; PERINATAL PERIOD; PHENOTYPE; WEIGHT GAIN; WEIGHT REDUCTION;

ANIMALS; BODY COMPOSITION; BODY WEIGHT; EATING; EMBRYONIC DEVELOPMENT; ENERGY METABOLISM; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GERM CELLS; HOMEOSTASIS; HUMANS; MALE; MICE; MIXED FUNCTION OXYGENASES; OBESITY; OXO-ACID-LYASES;

EID: 84873520661     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1003166     Document Type: Article

References (47)

1. Gerken T, Girard CA, Tung YCL, Webby CJ, Saudek V, et al. (2007) The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318: 1469-1472.
2. Han ZF, Niu TH, Chang JB, Lei XG, Zhao MY, et al. (2010) Crystal structure of the FTO protein reveals basis for its substrate specificity. Nature 464: 1205-U1129.
3. Jia GF, Fu Y, Zhao X, Dai Q, Zheng GQ, et al. (2011) N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nature Chemical Biology 7: 885-887.
4. Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, et al. (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316: 1341-1345.
5. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, 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.
6. Dina C, Meyre D, Gallina S, Durand E, Korner A, et al. (2007) Variation in FTO contributes to childhood obesity and severe adult obesity. Nature genetics 39: 724-726.
7. Scuteri A, Sanna S, Chen WM, Uda M, Albai G, et al. (2007) Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 3: e115 doi:10.1371/journal.pgen.0030115.
8. Fawcett KA, Barroso I, (2010) The genetics of obesity: FTO leads the way. Trends in genetics: TIG 26: 266-274.
9. Tung YC, Yeo GS, (2011) From GWAS to biology: lessons from FTO. Annals of the New York Academy of Sciences 1220: 162-171.
10. Sovio U, Mook-Kanamori DO, Warrington NM, Lawrence R, Briollais L, et al. (2011) Association between Common Variation at the FTO Locus and Changes in Body Mass Index from Infancy to Late Childhood: The Complex Nature of Genetic Association through Growth and Development. PLoS Genet 7: e1001307 doi:10.1371/journal.pgen.1001307.
11. Frayling TM, Ong K, (2011) Piecing together the FTO jigsaw. Genome biology 12: 104.
12. Hardy R, Wills AK, Wong A, Elks CE, Wareham NJ, et al. (2010) Life course variations in the associations between FTO and MC4R gene variants and body size. Human Molecular Genetics 19: 545-552.
13. Boissel S, Reish O, Proulx K, Kawagoe-Takaki H, Sedgwick B, et al. (2009) Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. American journal of human genetics 85: 106-111.
14. Meyre D, Proulx K, Kawagoe-Takaki H, Vatin V, Gutierrez-Aguilar R, et al. (2010) Prevalence of Loss-of-Function FTO Mutations in Lean and Obese Individuals. Diabetes 59: 311-318.
15. Timpson NJ, Emmett PM, Frayling TM, Rogers I, Hattersley AT, et al. (2008) The fat mass- and obesity-associated locus and dietary intake in children. American Journal of Clinical Nutrition 88: 971-978.
16. Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN, (2008) An obesity-associated FTO gene variant and increased energy intake in children. The New England journal of medicine 359: 2558-2566.
17. Tanofsky-Kraff M, Han JC, Anandalingam K, Shomaker LB, Columbo KM, et al. (2009) The FTO gene rs9939609 obesity-risk allele and loss of control over eating. American Journal of Clinical Nutrition 90: 1483-1488.
18. Wardle J, Carnell S, Haworth CMA, Farooqi IS, O'Rahilly S, et al. (2008) Obesity associated genetic variation in FTO is associated with diminished satiety. Journal of Clinical Endocrinology & Metabolism 93: 3640-3643.
19. den Hoed M, Westerterp-Plantenga MS, Bouwman FG, Mariman ECM, Westerterp KR, (2009) Postprandial responses in hunger and satiety are associated with the rs9939609 single nucleotide polymorphism in FTO. American Journal of Clinical Nutrition 90: 1426-1432.
20. Speakman JR, Rance KA, Johnstone AM, (2008) Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity 16: 1961-1965.
21. Haupt A, Thamer C, Staiger H, Tschritter O, Kirchhoff K, et al. (2009) Variation in the FTO Gene Influences Food Intake but not Energy Expenditure. Experimental and Clinical Endocrinology & Diabetes 117: 194-197.
22. Wardle J, Llewellyn C, Sanderson S, Plomin R, (2009) The FTO gene and measured food intake in children. International Journal of Obesity 33: 42-45.
23. Sonestedt E, Roos C, Gullberg B, Ericson U, Wirfalt E, et al. (2009) Fat and carbohydrate intake modify the association between genetic variation in the FTO genotype and obesity. American Journal of Clinical Nutrition 90: 1418-1425.
24. Lappalainen T, Lindstrom J, Paananen J, Eriksson JG, Karhunen L, et al. (2012) Association of the fat mass and obesity-associated (FTO) gene variant (rs9939609) with dietary intake in the Finnish Diabetes Prevention Study. The British journal of nutrition pp. 1-7 DOI: http://dx.doi.org/10.1017/S0007114511007410, Published online: 23 January 2012.
25. Ahmad T, Lee IM, Pare G, Chasman DI, Rose L, et al. (2011) Lifestyle interaction with fat mass and obesity-associated (FTO) genotype and risk of obesity in apparently healthy U.S. women. Diabetes care 34: 675-680.
26. Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, et al. (2009) Inactivation of the Fto gene protects from obesity. Nature 458: 894-U810.
27. Gao X, Shin YH, Li M, Wang F, Tong QA, et al. (2010) The Fat Mass and Obesity Associated Gene FTO Functions in the Brain to Regulate Postnatal Growth in Mice. PLoS ONE 5: e14005 doi:10.1371/journal.pone.0014005.
28. Speakman JR, (2010) FTO effect on energy demand versus food intake. Nature 464: E1; discussion E2.
29. Tschop MH, Speakman JR, Arch JRS, Auwerx J, Bruning JC, et al. (2012) A guide to analysis of mouse energy metabolism. Nature Methods 9: 57-63.
30. Kaiyala KJ, Schwartz MW, (2011) Toward a more complete (and less controversial) understanding of energy expenditure and its role in obesity pathogenesis. Diabetes 60: 17-23.
31. Church C, Lee S, Bagg EAL, McTaggart JS, Deacon R, et al. (2009) A Mouse Model for the Metabolic Effects of the Human Fat Mass and Obesity Associated FTO Gene. PLoS Genet 5: e1000599 doi:10.1371/journal.pgen.1000599.
32. Church C, Moir L, McMurray F, Girard C, Banks GT, et al. (2010) Overexpression of Fto leads to increased food intake and results in obesity. Nature genetics 42: 1086-U1147.
33. Tung YC, Ayuso E, Shan X, Bosch F, O'Rahilly S, et al. (2010) Hypothalamic-specific manipulation of Fto, the ortholog of the human obesity gene FTO, affects food intake in rats. PLoS ONE 5: e8771 doi:10.1371/journal.pone.0008771.
34. Butler AA, Kozak LP, (2010) A recurring problem with the analysis of energy expenditure in genetic models expressing lean and obese phenotypes. Diabetes 59: 323-329.
35. Choi SJ, Yablonka-Reuveni Z, Kaiyala KJ, Ogimoto K, Schwartz MW, et al. (2011) Increased energy expenditure and leptin sensitivity account for low fat mass in myostatin-deficient mice. American journal of physiology Endocrinology and metabolism 300: E1031-1037.
36. Cheung MK, Gulati P, O'Rahilly S, Yeo GS, (2012) FTO expression is regulated by availability of essential amino acids. International Journal of Obesity doi:10.1038/ijo.2012.77.
37. Dahlstrand J, Lardelli M, Lendahl U, (1995) Nestin mRNA expression correlates with the central nervous system progenitor cell state in many, but not all, regions of developing central nervous system. Brain research Developmental brain research 84: 109-129.
38. McTaggart JS, Lee S, Iberl M, Church C, Cox RD, et al. (2011) FTO Is Expressed in Neurones throughout the Brain and Its Expression Is Unaltered by Fasting. PLoS ONE 6: e27968 doi:10.1371/journal.pone.0027968.
39. Wang P, Yang FJ, Du H, Guan YF, Xu TY, et al. (2011) Involvement of leptin receptor long isoform (LepRb)-STAT3 signaling pathway in brain fat mass- and obesity-associated (FTO) downregulation during energy restriction. Molecular medicine 17: 523-532.
40. Stratigopoulos G, Padilla SL, LeDuc CA, Watson E, Hattersley AT, et al. (2008) Regulation of Fto/Ftm gene expression in mice and humans. American Journal of Physiology-Regulatory Integrative and Comparative Physiology 295: R1360-R1363.
41. Fredriksson R, Hagglund M, Olszewski PK, Stephansson O, Jacobsson JA, et al. (2008) The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. Endocrinology 149: 2062-2071.
42. Olszewski PK, Fredriksson R, Olszewska AM, Stephansson O, Alsio J, et al. (2009) Hypothalamic FTO is associated with the regulation of energy intake not feeding reward. BMC neuroscience 10: 129 doi:10.1186/1471-2202-10-129.
43. Wan ES, Cho MH, Boutaoui N, Klanderman BJ, Sylvia JS, et al. (2011) Genome-wide association analysis of body mass in chronic obstructive pulmonary disease. American journal of respiratory cell and molecular biology 45: 304-310.
44. Rodriguez CI, Buchholz F, Galloway J, Sequerra R, Kasper J, et al. (2000) High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nat Genet 25: 139-140.
45. Paxinos G, Franklin KBJ (2001) The Mouse Brain in Stereotaxic Coordinates. New York: Academic Press.
46. Diggle P, Heagerty P, Liang K-Y, Zeger SL (2002) Analysis of Longitudinal Data. Oxford: Oxford University press.
47. Pinheiro JC, Bates DM (2000) Mixed-Effects Models in S and S-Plus; Chambers J, Eddy W, Hardle W, Sheather S, Tierney L, editors. New York: Springer Verlag.