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J. Lipid Res.
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A more recent version of this article appeared on March 1, 2008

Papers In Press, published online ahead of print November 29, 2007
J. Lipid Res., doi:10.1194/jlr.M700448-JLR200
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Submitted on October 9, 2007
Revised on November 26, 2007
Accepted on November 28, 2007

The common rs9939609 gene variant of the fat mass and obesity associated gene (FTO) is related to fat cell lipolysis

Kerstin Wåhlén, Eva Sjölin, and Johan Hoffstedt

Department of Medicine, Karolinska Institutet, Stockholm 141 86

Corresponding Author: johan.hoffstedt{at}ki.se

We investigated the rs9939609 single nucleotide polymorphism (SNP) of the FTO gene in relation to fat cell function and adipose tissue gene expression in 306 healthy women with a wide range in BMI (18-53 kg/m2). Subcutaneous adipose tissue biopsies were taken for fat cell metabolism studies and in a subgroup (n=90) for gene expression analyses. In homozygous carriers of the T-allele, the in vitro basal (spontaneous) adipocyte glycerol release was increased by 22% (p=0.007) and the in vivo plasma glycerol level was increased 30% (p=0.037) as compared to carriers of the A-allele. In contrast, there were no genotype effects on catecholamine-stimulated lipolysis or basal or insulin-induced lipogenesis. We found no difference between genotypes for adipose tissue mRNA levels of FTO, hormone sensitive lipase, adipose triglyceride lipase, perilipin or CGI-58. Finally, the adipose tissue level of FTO mRNA was increased in obesity (p=0.002), was similar in subcutaneous and omental adipose tissue, was higher in fat cells than in fat tissue (p=0.0007) and was induced at an early stage in the differentiation process (p=0.004). These data suggest a role of the FTO gene in fat cell lipolysis, which may be important in explaining why the gene is implicated in body weight regulation.


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