J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M700448-JLR200 on November 29, 2007

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Journal of Lipid Research, Vol. 49, 607-611, March 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

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 Hoffstedt1

Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

Published, JLR Papers in Press, November 29, 2007.

1 To whom correspondence should be addressed. e-mail: johan.hoffstedt{at}ki.se

We investigated the rs9939609 single nucleotide polymorphism of the FTO gene in relation to fat cell function and adipose tissue gene expression in 306 healthy women with a wide range in body mass index (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 by ~30% (P = 0.037) compared with 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.

Supplementary key words adipocyte • lipid and glucose metabolism • messenger RNA • single nucleotide polymorphism




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