Horm Metab Res 2011; 43(1): 17-21
DOI: 10.1055/s-0030-1265130
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Regulation of FTO and FTM Expression During Human Preadipocyte Differentiation

D. Tews1 , P. Fischer-Posovszky1 , M. Wabitsch1
  • 1Division of Pediatric Endocrinology and Diabetes, Endocrine Research Laboratory, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany
Further Information

Publication History

received 22.06.2010

accepted 10.08.2010

Publication Date:
23 September 2010 (online)

Abstract

In genome-wide association studies (GWAS), polymorphisms in the first intron of FTO were shown to be associated with body fat mass. However, the functional properties of FTO and its nearby gene FTM are largely unknown. We examined the expression of these genes in subcutaneous adipose tissue and in isolated preadipocytes of lean and obese women. In in vitro differentiated primary human preadipocytes and in SGBS preadipocytes we found a decline in FTO and FTM expression during adipogenic differentiation. When investigating the hormonal regulation of FTO and FTM in adipocytes, insulin was identified as a key factor regulating FTM expression indicating a potential role of FTM in insulin regulated adipocyte metabolism.

References

  • 1 Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes.  Nature. 2006;  444 840-846
  • 2 Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease.  Nature. 2006;  444 875-880
  • 3 Bray GA, Bellanger T. Epidemiology, trends, and morbidities of obesity and the metabolic syndrome.  Endocrine. 2006;  29 109-117
  • 4 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
  • 5 Maes HH, Neale MC, Eaves LJ. Genetic and environmental factors in relative body weight and human adiposity.  Behav Genet. 1997;  27 325-351
  • 6 Tews D, Fischer-Posovszky P, Wabitsch M. FTO – Friend or foe?.  Horm Metab Res. 2010;  42 75-80
  • 7 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
  • 8 Berulava T, Horsthemke B. The obesity-associated SNPs in intron 1 of the FTO gene affect primary transcript levels.  Eur J Hum Genet. 2010;  May 26[Epub ahead of print]
  • 9 Berulava T, Horsthemke B. Comment on: Jowett et al. Genetic variation at the FTO locus influences RBL2 gene expression.  Diabetes. 2010;  59 726-732 Diabetes 2010; 59: e9; authors’ reply e10
  • 10 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
  • 11 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
  • 12 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
  • 13 Han Z, Niu T, Chang J, Lei X, Zhao M, Wang Q, Cheng W, Wang J, Feng Y, Chai J. Crystal structure of the FTO protein reveals basis for its substrate specificity.  Nature. 2010;  464 1205-1209
  • 14 Delous M, Baala L, Salomon R, Laclef C, Vierkotten J, Tory K, Golzio C, Lacoste T, Besse L, Ozilou C, Moutkine I, Hellman NE, Anselme I, Silbermann F, Vesque C, Gerhardt C, Rattenberry E, Wolf MT, Gubler MC, Martinovic J, Encha-Razavi F, Boddaert N, Gonzales M, Macher MA, Nivet H, Champion G, Bertheleme JP, Niaudet P, McDonald F, Hildebrandt F, Johnson CA, Vekemans M, Antignac C, Ruther U, Schneider-Maunoury S, Attie-Bitach T, Saunier S. The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome.  Nat Genet. 2007;  39 875-881
  • 15 Vierkotten J, Dildrop R, Peters T, Wang B, Ruther U. Ftm is a novel basal body protein of cilia involved in Shh signalling.  Development. 2007;  134 2569-2577
  • 16 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
  • 17 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
  • 18 Grunnet LG, Nilsson E, Ling C, Hansen T, Pedersen O, Groop L, Vaag A, Poulsen P. Regulation and function of FTO mRNA expression in human skeletal muscle and subcutaneous adipose tissue.  Diabetes. 2009;  58 2402-2408
  • 19 Zabena C, Gonzalez-Sanchez JL, Martinez-Larrad MT, Torres-Garcia A, Alvarez-Fernandez-Represa J, Corbaton-Anchuelo A, Perez-Barba M, Serrano-Rios M. The FTO Obesity Gene. Genotyping and Gene Expression Analysis in Morbidly Obese Patients.  Obes Surg. 2009;  19 87-95
  • 20 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
  • 21 Hauner H, Skurk T, Wabitsch M. Cultures of human adipose precursor cells.  Methods Mol Biol. 2001;  155 239-247
  • 22 Wabitsch M, Brenner RE, Melzner I, Braun M, Möller P, Heinze E, Debatin KM, Hauner H. Characterization of a human preadipocyte cell strain with high capacity for adipose differentiation.  Int J Obes Relat Metab Disord. 2001;  25 8-15
  • 23 Marshall OJ. PerlPrimer: cross-platform, graphical primer design for standard, bisulphite and real-time PCR.  Bioinformatics. 2004;  20 2471-2472
  • 24 Fischer-Posovszky P, Newell FS, Wabitsch M, Tornqvist HE. Human SGBS Cells – a Unique Tool for Studies of Human Fat Cell Biology.  Obes Facts. 2008;  1 184-189
  • 25 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
  • 26 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
  • 27 Liu F, Fan H, Qiu J, Wang B, Zhang M, Gu N, Zhang C, Fei L, Pan X, Guo M, Chen R, Guo X. A paradox: insulin inhibits expression and secretion of resistin which induces insulin resistance.  World J Gastroenterol. 2008;  14 95-100
  • 28 Ahlzen M, Johansson LE, Cervin C, Tornqvist H, Groop L, Ridderstrale M. Expression of the transcription factor 7-like 2 gene (TCF7L2) in human adipocytes is down regulated by insulin.  Biochem Biophys Res Commun. 2008;  370 49-52
  • 29 Zhu D, Shi S, Wang H, Liao K. Growth arrest induces primary-cilium formation and sensitizes IGF-1-receptor signaling during differentiation induction of 3T3-L1 preadipocytes.  J Cell Sci. 2009;  122 (Pt 15) 2760-2768
  • 30 Spinella-Jaegle S, Rawadi G, Kawai S, Gallea S, Faucheu C, Mollat P, Courtois B, Bergaud B, Ramez V, Blanchet AM, Adelmant G, Baron R, Roman-Roman S. Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation.  J Cell Sci. 2001;  114 (Pt 11) 2085-2094
  • 31 Riobó NA, Lu K, Ai X, Haines GM, Emerson CP. Phosphoinositide 3-kinase and Akt are essential for Sonic Hedgehog signaling.  Proc Natl Acad Sci USA. 2006;  103 4505-4510

Correspondence

Prof. Dr. M. Wabitsch

Division of Pediatric Endocrinology

and Diabetes

Department of Pediatrics and

Adolescent Medicine

University of Ulm

Eythstraße 24

89075 Ulm

Germany

Phone: +49/731/500 57401

Fax: +49/731/500 57407

Email: martin.wabitsch@uniklinik-ulm.de

    >