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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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