Abstract
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/m(2)). 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 approximately 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.
Highlights
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)
In searching for gene variation implicated in obesity development, the recent discoveries of strong associations with obesity of common single nucleotide polymorphisms (SNPs) in the fat mass- and obesity-associated gene FTO in large populations are of particular interest
We demonstrate that healthy women, who are homozygous for the more common obesity-protective FTO allele, have ?30% increased in vivo lipolytic activity compared with other genotypes, independent of body mass index (BMI)
Summary
Copyright D 2008 by the American Society for Biochemistry and Molecular Biology, Inc. This article is available online at http://www.jlr.org. This article is available online at http://www.jlr.org At ?7:30 AM after an overnight fast, a venous blood sample was obtained for DNA extraction and for analyses of plasma levels of glucose, insulin, triglycerides, cholesterol, HDL cholesterol, and glycerol, which were performed by the hospital’s accredited chemistry laboratory. Measurement of total body fat was obtained by a formula based on age, BMI, and sex [5]. This formula is accurate compared with more direct estimates of body fat content [6]. The study was approved by the ethics committee at Karolinska University Hospital, and informed consent was obtained from all participants
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