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DOI: 10.1055/s-0029-1241831
© Georg Thieme Verlag KG Stuttgart · New York
FTO – Friend or Foe?
Publikationsverlauf
received 20.07.2009
accepted 08.10.2009
Publikationsdatum:
18. November 2009 (online)

Abstract
Fat mass and obesity associated gene (FTO) is the most relevant polygene for obesity to date. It has been identified by genome wide association studies concerning body weight regulation. However, its functional relevance for the pathogenesis of obesity remains elusive. Studies in rodents provide data pointing to a central role of FTO through regulation of food intake. In addition, peripheral effects of FTO are also discussed in the literature. This review highlights the possible relevance of FTO for weight regulation and obesity development in central and peripheral tissues with a special focus on adipose tissue.
Key words
adipose tissue - obesity - body weight
References
- 1
Wardle J, Carnell S, Haworth CM, Plomin R.
Evidence for a strong genetic influence on childhood adiposity despite the force of
the obesogenic environment.
Am J Clin Nutr.
2008;
87
398-404
Reference Ris Wihthout Link
- 2
Maes HH, Neale MC, Eaves LJ.
Genetic and environmental factors in relative body weight and human adiposity.
Behav Genet.
1997;
27
325-351
Reference Ris Wihthout Link
- 3
Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI.
A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity.
Science.
2007;
316
889-894
Reference Ris Wihthout Link
- 4
Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, Najjar S, Nagaraja R, Orru M, Usala G, Dei M, Lai S, Maschio A, Busonero F, Mulas A, Ehret GB, Fink AA, Weder AB, Cooper RS, Galan P, Chakravarti A, Schlessinger D, Cao A, Lakatta E, Abecasis GR.
Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits.
PLoS Genet.
2007;
3
e115
Reference Ris Wihthout Link
- 5
Dina C, Meyre D, Gallina S, Durand E, Korner A, Jacobson P, Carlsson LM, Kiess W, Vatin V, Lecoeur C, Delplanque J, Vaillant E, Pattou F, Ruiz J, Weill J, Levy-Marchal C, Horber F, Potoczna N, Hercberg S, Le Stunff C, Bougneres P, Kovacs P, Marre M, Balkau B, Cauchi S, Chevre JC, Froguel P.
Variation in FTO contributes to childhood obesity and severe adult obesity.
Nat Genet.
2007;
39
724-726
Reference Ris Wihthout Link
- 6
Hinney A, Nguyen TT, Scherag A, Friedel S, Bronner G, Muller TD, Grallert H, Illig T, Wichmann HE, Rief W, Schafer H, Hebebrand J.
Genome wide association (GWA) study for early onset extreme obesity supports the role
of fat mass and obesity associated gene (FTO) variants.
PLoS ONE.
2007;
2
e1361
Reference Ris Wihthout Link
- 7
Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, Styrkarsdottir U, Gretarsdottir S, Thorlacius S, Jonsdottir I, Jonsdottir T, Olafsdottir EJ, Olafsdottir GH, Jonsson T, Jonsson F, Borch-Johnsen K, Hansen T, Andersen G, Jorgensen T, Lauritzen T, Aben KK, Verbeek AL, Roeleveld N, Kampman E, Yanek LR, Becker LC, Tryggvadottir L, Rafnar T, Becker DM, Gulcher J, Kiemeney LA, Pedersen O, Kong A, Thorsteinsdottir U, Stefansson K.
Genome-wide association yields new sequence variants at seven loci that associate
with measures of obesity.
Nat Genet.
2009;
41
18-24
Reference Ris Wihthout Link
- 8
Li H, Wu Y, Loos RJ, Hu FB, Liu Y, Wang J, Yu Z, Lin X.
Variants in the fat mass- and obesity-associated (FTO) gene are not associated with obesity in a Chinese Han population.
Diabetes.
2008;
57
264-268
Reference Ris Wihthout Link
- 9
Ohashi J, Naka I, Kimura R, Natsuhara K, Yamauchi T, Furusawa T, Nakazawa M, Ataka Y, Patarapotikul J, Nuchnoi P, Tokunaga K, Ishida T, Inaoka T, Matsumura Y, Ohtsuka R.
FTO polymorphisms in oceanic populations.
J Hum Genet.
2007;
52
1031-1035
Reference Ris Wihthout Link
- 10
Horikoshi M, Hara K, Ito C, Shojima N, Nagai R, Ueki K, Froguel P, Kadowaki T.
Variations in the HHEX gene are associated with increased risk of type 2 diabetes
in the Japanese population.
Diabetologia.
2007;
50
2461-2466
Reference Ris Wihthout Link
- 11
Cha SW, Choi SM, Kim KS, Park BL, Kim JR, Kim JY, Shin HD.
Replication of Genetic Effects of FTO Polymorphisms on BMI in a Korean Population.
Obesity (Silver Spring).
2008;
16
2187-2189
Reference Ris Wihthout Link
- 12
Chang YC, Liu PH, Lee WJ, Chang TJ, Jiang YD, Li HY, Kuo SS, Lee KC, Chuang LM.
Common variation in the fat mass and obesity-associated (FTO) gene confers risk of obesity and modulates BMI in the Chinese population.
Diabetes.
2008;
57
2245-2252
Reference Ris Wihthout Link
- 13
Tan JT, Dorajoo R, Seielstad M, Sim XL, Ong RT, Chia KS, Wong TY, Saw SM, Chew SK, Aung T, Tai ES.
FTO variants are associated with obesity in the Chinese and Malay populations in Singapore.
Diabetes.
2008;
57
2851-2857
Reference Ris Wihthout Link
- 14
Hotta K, Nakata Y, Matsuo T, Kamohara S, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Masuzaki H, Yoneda M, Nakajima A, Miyazaki S, Tokunaga K, Kawamoto M, Funahashi T, Hamaguchi K, Yamada K, Hanafusa T, Oikawa S, Yoshimatsu H, Nakao K, Sakata T, Matsuzawa Y, Tanaka K, Kamatani N, Nakamura Y.
Variations in the FTO gene are associated with severe obesity in the Japanese.
J Hum Genet.
2008;
53
546-553
Reference Ris Wihthout Link
- 15
Al-Attar SA, Pollex RL, Ban MR, Young TK, Bjerregaard P, Anand SS, Yusuf S, Zinman B, Harris SB, Hanley AJ, Connelly PW, Huff MW, Hegele RA.
Association between the FTO rs9939609 polymorphism and the metabolic syndrome in a non-Caucasian multi-ethnic
sample.
Cardiovasc Diabetol.
2008;
7
5
Reference Ris Wihthout Link
- 16
Hennig BJ, Fulford AJ, Sirugo G, Rayco-Solon P, Hattersley AT, Frayling TM, Prentice AM.
FTO gene variation and measures of body mass in an African population.
BMC Med Genet.
2009;
10
21
Reference Ris Wihthout Link
- 17
Qi L, Kang K, Zhang C, van Dam RM, Kraft P, Hunter D, Lee CH, Hu FB.
Fat mass-and obesity-associated (FTO) gene variant is associated with obesity: longitudinal analyses in two cohort studies
and functional test.
Diabetes.
2008;
57
3145-3151
Reference Ris Wihthout Link
- 18
Lopez-Bermejo A, Petry CJ, Diaz M, Sebastiani G, de Zegher F, Dunger DB, Ibanez L.
The association between the FTO gene and fat mass in humans develops by the postnatal age of two weeks.
J Clin Endocrinol Metab.
2008;
93
1501-1505
Reference Ris Wihthout Link
- 19
Haworth CM, Carnell S, Meaburn EL, Davis OS, Plomin R, Wardle J.
Increasing heritability of BMI and stronger associations with the FTO gene over childhood.
Obesity (Silver Spring).
2008;
16
2663-2668
Reference Ris Wihthout Link
- 20
Peeters A, Beckers S, Verrijken A, Roevens P, Peeters P, Van Gaal L, Van Hul W.
Variants in the FTO gene are associated with common obesity in the Belgian population.
Mol Genet Metab.
2008;
93
481-484
Reference Ris Wihthout Link
- 21
Andreasen CH, Stender-Petersen KL, Mogensen MS, Torekov SS, Wegner L, Andersen G, Nielsen AL, Albrechtsen A, Borch-Johnsen K, Rasmussen SS, Clausen JO, Sandbaek A, Lauritzen T, Hansen L, Jorgensen T, Pedersen O, Hansen T.
Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation.
Diabetes.
2008;
57
95-101
Reference Ris Wihthout Link
- 22
Herder C, Rathmann W, Strassburger K, Finner H, Grallert H, Huth C, Meisinger C, Gieger C, Martin S, Giani G, Scherbaum WA, Wichmann HE, Illig T.
Variants of the PPARG, IGF2BP2, CDKAL1, HHEX, and TCF7L2 genes confer risk of type
2 diabetes independently of BMI in the German KORA studies.
Horm Metab Res.
2008;
40
722-726
Reference Ris Wihthout Link
- 23
Zimmermann E, Kring SI, Berentzen TL, Holst C, Pers TH, Hansen T, Pedersen O, Sorensen TI, Jess T.
Fatness-associated FTO gene variant increases mortality independent of fatness – in cohorts of Danish men.
PLoS ONE.
2009;
4
e4428
Reference Ris Wihthout Link
- 24
Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC, Ruther U.
Inactivation of the FTO gene protects from obesity.
Nature.
2009;
458
894-898
Reference Ris Wihthout Link
- 25
Peters T, Ausmeier K, Dildrop R, Ruther U.
The mouse Fused toes (Ft) mutation is the result of a 1.6-Mb deletion including the
entire Iroquois B gene cluster.
Mamm Genome.
2002;
13
186-188
Reference Ris Wihthout Link
- 26
Peters T, Ausmeier K, Ruther U.
Cloning of Fatso (FTO), a novel gene deleted by the Fused toes (Ft) mouse mutation.
Mamm Genome.
1999;
10
983-986
Reference Ris Wihthout Link
- 27
Gotz K, Briscoe J, Ruther U.
Homozygous Ft embryos are affected in floor plate maintenance and ventral neural tube
patterning.
Dev Dyn.
2005;
233
623-630
Reference Ris Wihthout Link
- 28
Grotewold L, Ruther U.
The Fused toes (Ft) mouse mutation causes anteroposterior and dorsoventral polydactyly.
Dev Biol.
2002;
251
129-141
Reference Ris Wihthout Link
- 29
Heymer J, Kuehn M, Ruther U.
The expression pattern of nodal and lefty in the mouse mutant Ft suggests a function
in the establishment of handedness.
Mech Dev.
1997;
66
5-11
Reference Ris Wihthout Link
- 30
van der , Schimmang T, Volkmann A, Mattei MG, Kyewski B, Ruther U.
Programmed cell death is affected in the novel mouse mutant Fused toes (Ft).
Development.
1994;
120
2601-2607
Reference Ris Wihthout Link
- 31
Church C, Lee S, Bagg EA, McTaggart JS, Deacon R, Gerken T, Lee A, Moir L, Mecinovic J, Quwailid MM, Schofield CJ, Ashcroft FM, Cox RD.
A mouse model for the metabolic effects of the human fat mass and obesity associated
FTO gene.
PLoS Genet.
2009;
5
e1000599
Reference Ris Wihthout Link
- 32
Boissel S, Reish O, Proulx K, Kawagoe-Takaki H, Sedgwick B, Yeo GS, Meyre D, Golzio C, Molinari F, Kadhom N, Etchevers HC, Saudek V, Farooqi IS, Froguel P, Lindahl T, O’Rahilly S, Munnich A, Colleaux L.
Loss-of-Function Mutation in the Dioxygenase-Encoding FTO Gene Causes Severe Growth Retardation and Multiple Malformations.
Am J Hum Genet.
2009;
85
106-111
Reference Ris Wihthout Link
- 33
Stratigopoulos G, Padilla SL, LeDuc CA, Watson E, Hattersley AT, McCarthy MI, Zeltser LM, Chung WK, Leibel RL.
Regulation of FTO/FTM gene expression in mice and humans.
Am J Physiol Regul Integr Comp Physiol.
2008;
294
R1185-R1196
Reference Ris Wihthout Link
- 34
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.
The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase.
Science.
2007;
318
1469-1472
Reference Ris Wihthout Link
- 35
Sanchez-Pulido L, Andrade-Navarro MA.
The FTO (fat mass and obesity associated) gene codes for a novel member of the non-heme dioxygenase
superfamily.
BMC Biochem.
2007;
8
23
Reference Ris Wihthout Link
- 36
Ozer A, Bruick RK.
Non-heme dioxygenases: cellular sensors and regulators jelly rolled into one?.
Nat Chem Biol.
2007;
3
144-153
Reference Ris Wihthout Link
- 37
Jia G, Yang CG, Yang S, Jian X, Yi C, Zhou Z, He C.
Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA
and RNA by mouse and human FTO.
FEBS Lett.
2008;
582
3313-3319
Reference Ris Wihthout Link
- 38
Gemma C, Sookoian S, Alvarinas J, Garcia SI, Quintana L, Kanevsky D, Gonzalez CD, Pirola CJ.
Maternal pregestational BMI is associated with methylation of the PPARGC1A promoter
in newborns.
Obesity (Silver Spring).
2009;
17
1032-1039
Reference Ris Wihthout Link
- 39
Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN.
An obesity-associated FTO gene variant and increased energy intake in children.
N Engl J Med.
2008;
359
2558-2566
Reference Ris Wihthout Link
- 40
Wardle J, Carnell S, Haworth CM, Farooqi IS, O’Rahilly S, Plomin R.
Obesity associated genetic variation in FTO is associated with diminished satiety.
J Clin Endocrinol Metab.
2008;
93
3640-3643
Reference Ris Wihthout Link
- 41
Wardle J, Llewellyn C, Sanderson S, Plomin R.
The FTO gene and measured food intake in children.
Int J Obes (Lond).
2009;
33
42-45
Reference Ris Wihthout Link
- 42
Berentzen T, Kring SI, Holst C, Zimmermann E, Jess T, Hansen T, Pedersen O, Toubro S, Astrup A, Sorensen TI.
Lack of association of fatness-related FTO gene variants with energy expenditure or physical activity.
J Clin Endocrinol Metab.
2008;
93
2904-2908
Reference Ris Wihthout Link
- 43
Fredriksson R, Hagglund M, Olszewski PK, Stephansson O, Jacobsson JA, Olszewska AM, Levine AS, Lindblom J, Schioth HB.
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.
2008;
149
2062-2071
Reference Ris Wihthout Link
- 44
Tschritter O, Preissl H, Hennige AM, Stumvoll M, Porubska K, Frost R, Marx H, Klosel B, Lutzenberger W, Birbaumer N, Haring HU, Fritsche A.
The cerebrocortical response to hyperinsulinemia is reduced in overweight humans:
a magnetoencephalographic study.
Proc Natl Acad Sci U S A.
2006;
103
12103-12108
Reference Ris Wihthout Link
- 45
Tschritter O, Preissl H, Yokoyama Y, Machicao F, Haring HU, Fritsche A.
Variation in the FTO gene locus is associated with cerebrocortical insulin resistance in humans.
Diabetologia.
2007;
50
2602-2603
Reference Ris Wihthout Link
- 46
Grunnet LG, Brons C, Jacobsen S, Nilsson E, Astrup A, Hansen T, Pedersen O, Poulsen P, Quistorff B, Vaag A.
Increased recovery rates of phosphocreatine and inorganic phosphate after isometric
contraction in oxidative muscle fibers and elevated hepatic insulin resistance in
homozygous carriers of the A-allele of FTO rs939609.
J Clin Endocrinol Metab.
2009;
94
596-602
Reference Ris Wihthout Link
- 47
Hotamisligil GS.
Inflammation and metabolic disorders.
Nature.
2006;
444
860-867
Reference Ris Wihthout Link
- 48
Fischer-Posovszky P, Wabitsch M, Hochberg Z.
Endocrinology of adipose tissue - an update.
Horm Metab Res.
2007;
39
314-321
Reference Ris Wihthout Link
- 49
Kloting N, Schleinitz D, Ruschke K, Berndt J, Fasshauer M, Tonjes A, Schon MR, Kovacs P, Stumvoll M, Bluher M.
Inverse relationship between obesity and FTO gene expression in visceral adipose tissue in humans.
Diabetologia.
2008;
51
641-647
Reference Ris Wihthout Link
- 50
Wahlen K, Sjolin E, Hoffstedt J.
The common rs9939609 gene variant of the fat mass- and obesity-associated gene FTO is related to fat cell lipolysis.
J Lipid Res.
2008;
49
607-611
Reference Ris Wihthout Link
Correspondence
Dr. D. Tews
Division of Pediatric
Endocrinology and Diabetes
Endocrine Research Laboratory
Department of Pediatrics and Adolescent Medicine
University of Ulm
Eythstraße24
89075 Ulm
Germany
Telefon: +49 731 500 57264
Fax: +49 731 500 57246
eMail: daniel.tews@uniklinik-ulm.de
