P R O D UC T FLYERFTO

A Gene Contributing to Human Obesity

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To date it is known that genetic factors play a decisiverole in influencing which individuals become obese ina particular environment [1, 2]. A major breakthroughin this field was the recent discovery of the FTO (fatmass and obesity associated) gene through genomewide association, the latest gene-finding strategy [3].
Widely replicated evidence has reconfirmed that variants of the FTO gene are associated with obesity in thecommon population.
The identification of the FTO gene was reported first inconjunction with a mutation in mice characterized byfused toes (FTO) [4]. The connection of the FTO genewith obesity was discovered only recently in a type2 diabetes study with over 2000 diabetics [3]. It was
found that sequence variants of the FTO gene can belinked to increased bodyweight of the tested subjects
and that the effect of the FTO gene variants on obesity
is dose dependent. This finding was reproduced formany caucasian populations [1, 5, 6, 7, 8]. The influence of the FTO gene variants on obesity is relatively
consistent throughout all these studies.
Particular FTO gene variants are also associated withother diseases such as the metabolic syndrome (MetS)
and diabetes [3, 9, 10, 11]. However all these effects
appear to be secondary to weight increase since theassociation is completely abolished after adjusting thebody mass index (BMI).
It is not clear yet how the observed effect of the FTO
gene variants on obesity is exerted. The FTO gene is avery large gene of more than 400kb on human chromosome 16 and is well conserved in vertebrates andalgae [12, 13, 14]. Four regions in the gene are particularly well conserved and three of them are homologous to AlkB, a member of the 2OG-Fe(II) oxygenase superfamily that oxidatively demethylates DNA[12, 13]. 2OG-Fe(II) oxygenases are involved in diverse
processes such as DNA repair, fatty acid metabolism,and posttranslational modifications [15]. Indeed, invitro studies with the recombinant FTO protein showthat 3-methylthymine DNA seems to be a substrateof FTO [12]. Consistent with a potential role in nucleic
acid demethylation, the FTO protein was found to lo-International Edition

calize to the nucleus [12]. However, it remains to beshown if an altered demethylase activity causes thelink of BMI with the FTO gene variants.
On the level of the whole organism the FTO protein
shows wide expression patterns in peripheral as wellas central tissues with a high expression in the brain[3, 12, 16, 17]. In mice it was observed that the mRNAwas up-regulated by feeding and down-regulated byfasting [16, 12]. These findings together hint that theFTO protein may be involved in regulating food intake
by its action in the corresponding brain areas. Otherstudies that investigated the relative rates of the FTO
protein expression in adipose tissue subfractions, however, point to a role of FTO on the level of the adipose
tissue [18, 19].
LIT: [1] FTO: the first gene contributing to common forms of human obesity: R.J.
Loos & C. Bouchard; Obes. Rev. 9, 246 (2008)  [2] Obesity--is it a genetic disorder?: R.J. Loos & C. Bouchard; J. Intern. Med. 254, 401 (2003)  [3] A common
variant in the FTO gene is associated with body mass index and predisposes
to childhood and adult obesity: T.M. Frayling, et al., Science 316, 889 (2007) [4] Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse
mutation: T. Peters, et al.; Mamm. Genome 10, 983 (1999)  [5] Genome-wide
association scan shows genetic variants in the FTO gene are associated withobesity-related traits: A. Scuteri, et al.; PLoS Genet. 3, e115 (2007)  [6] Variation
in FTO contributes to childhood obesity and severe adult obesity: C. Dina, etal.; Nat. Genet. 39, 724 (2007)  [7] A genome-wide association study of type2 diabetes in Finns detects multiple susceptibility variants: L.J. Scott, et al.;Science 316, 1341 (2007)  [8] Major gender difference in association of FTO
gene variant among severely obese children with obesity and obesity related
phenotypes: J.A. Jacobsson, et al.; BBRC 368, 476 (2008)  [9] Association between the FTO rs9939609 polymorphism and the metabolic syndrome in a
non-Caucasian multi-ethnic sample: S.A. Al-Attar, et al.; Cardiovasc. Diabetol.
7, 5 (2008)  [10] Common variation in the FTO gene alters diabetes-related
metabolic traits to the extent expected given its effect on BMI: R.M. Freathy,et al.; Diabetes 57, 1419 (2008)  [11] Variations in the HHEX gene are associated with increased risk of type 2 diabetes in the Japanese population: M.
Horikoshi, et al.; Diabetologia 50, 2461 (2007)  [12] The obesity-associated
FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase: T.
Gerken, et al.; Science 318, 1469 (2007)  [13] The FTO (fat mass and obesityassociated) gene codes for a novel member of the non-heme dioxygenase superfamily: L. Sanchez-Pulido, et al.; BMC Biochem. 8, 23 (2007)  [14] The FTO
gene, implicated in human obesity, is found only in vertebrates and marine
algae: S. Robbens, et al.; J. Mol. Evol. 66, 80 (2008)  [15] Structural studies on
2-oxoglutarate oxygenases and related double-stranded beta-helix fold proteins: I.J. Clifton, et al.; J. Inorg. Biochem. 100, 644 (2006)  [16] Regulation ofFto/Ftm gene expression in mice and humans: G. Stratigopoulos, et al.; Am.
J. Physiol. Regul. Integr. Comp. Physiol. 294, R1185 (2008)  [17] The obesity
gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain: R. Fredriksson, et al.;Endocrinology 149, 2062 (2008)  [18] The common rs9939609 gene variantof the fat mass- and obesity-associated gene FTO is related to fat cell lipolysis: K. Wahlen, et al.; J. Lipid Res. 49, 607 (2008)  [19] Inverse relationship between obesity and FTO gene expression in visceral adipose tissue in humans:
N. Klöting, et al.; Diabetologia 51, 641 (2008)

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FTO (human) (rec.) (His)[Fat Mass and Obesity-associated Protein (human) (rec.)(His); FATSO (human) (rec.) (His)]

ALX-201-421-C010
10 μg
ALX-201-421-C050
50 μg
SOURCE/HOST: Expressed in E. coli. The mature
peptide of human FTP (aa 2-505) is fused atthe N-terminus to a His-tag.
PURITY: ≥90% (SDS-PAGE).
ENDOTOXIN CONTENT: <1EU/μg protein (LAL-test).
CONCENTRATION: 0.5mg/ml.
FIGURE: SDS-PAGE of FTO (human) (rec.) (His) (Prod. No. ALX-201-421)

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