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DOI: 10.1055/s-0030-1265130
© Georg Thieme Verlag KG Stuttgart · New York
Regulation of FTO and FTM Expression During Human Preadipocyte Differentiation
Publikationsverlauf
received 22.06.2010
accepted 10.08.2010
Publikationsdatum:
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.
Key words
fat cell - obesity - human adipose tissue - adipogenesis
References
- 1
Kahn SE, Hull RL, Utzschneider KM.
Mechanisms linking obesity to insulin resistance and type 2 diabetes.
Nature.
2006;
444
840-846
MissingFormLabel
- 2
Van Gaal LF, Mertens IL, De Block CE.
Mechanisms linking obesity with cardiovascular disease.
Nature.
2006;
444
875-880
MissingFormLabel
- 3
Bray GA, Bellanger T.
Epidemiology, trends, and morbidities of obesity and the metabolic syndrome.
Endocrine.
2006;
29
109-117
MissingFormLabel
- 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
MissingFormLabel
- 5
Maes HH, Neale MC, Eaves LJ.
Genetic and environmental factors in relative body weight and human adiposity.
Behav Genet.
1997;
27
325-351
MissingFormLabel
- 6
Tews D, Fischer-Posovszky P, Wabitsch M.
FTO – Friend or foe?.
Horm Metab Res.
2010;
42
75-80
MissingFormLabel
- 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
MissingFormLabel
- 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]
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 21
Hauner H, Skurk T, Wabitsch M.
Cultures of human adipose precursor cells.
Methods Mol Biol.
2001;
155
239-247
MissingFormLabel
- 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
MissingFormLabel
- 23
Marshall OJ.
PerlPrimer: cross-platform, graphical primer design for standard, bisulphite and real-time
PCR.
Bioinformatics.
2004;
20
2471-2472
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
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
Telefon: +49/731/500 57401
Fax: +49/731/500 57407
eMail: martin.wabitsch@uniklinik-ulm.de