Abstract
Central fat accumulation is a strong risk factor for type 2 diabetes. Genome-wide association studies have identified numerous loci associated with body fat distribution. The objectives of the current study are to examine whether genes in genetic loci linked to fat distribution can be linked to fat cell size and number (morphology) and/or adipose tissue function. We show, in a cohort of 114 women, that almost half of the 96 genes in these loci are indeed associated with abdominal subcutaneous adipose tissue parameters. Thus, adipose mRNA expression of the genes is strongly related to adipose morphology, catecholamine-induced lipid mobilization (lipolysis), or insulin-stimulated lipid synthesis in adipocytes (lipogenesis). In conclusion, the genetic influence on body fat distribution could be mediated via several specific alterations in adipose tissue morphology and function, which in turn may influence the development of type 2 diabetes.
Highlights
Central fat accumulation is a strong risk factor for type 2 diabetes
The ability of insulin to stimulate fat synthesis through glucose conversion into lipids could be of importance. We investigated whether these adipocyte phenotypes could be linked to abdominal subcutaneous white adipose tissue (WAT) expression of 96 candidate genes in the vicinity of the recently described genetic loci for body fat distribution [3]
We focused on genome-wide association (GWA) candidates for body fat distribution; that is, all genes that were localized within 250 kb of the lead single nucleotide polymorphism in the loci associated with body fat distribution listed by Shungin et al [3] in their Tables 1, 2, and 3
Summary
Central fat accumulation is a strong risk factor for type 2 diabetes. Genome-wide association studies have identified numerous loci associated with body fat distribution. The objectives of the current study are to examine whether genes in genetic loci linked to fat distribution can be linked to fat cell size and number (morphology) and/or adipose tissue function. We investigated whether these adipocyte phenotypes (adipose morphology, lipolysis, and lipogenesis) could be linked to abdominal subcutaneous white adipose tissue (WAT) expression of 96 candidate genes in the vicinity of the recently described genetic loci for body fat distribution [3]. This centrally located adipose region contributes to variations in WHR and in other parameters of body fat distribution. Adipose hypertrophy is linked to insulin resistance and the development of type 2 diabetes, as discussed [10]
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