Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor-gamma2 gene with obesity in two Caucasian populations.

作者：Brock A. Beamer, Chung‐Jen Yen, Ross E. Andersen, D Muller, Dariush Elahi, Lawrence Jay Cheskin, R Andres, Jesse Roth, Alan R. Shuldiner · 发表于：Diabetes · 年份：1998 · DOI：10.2337/diabetes.47.11.1806 · 被引用次数：293 · 研究领域：Peroxisome Proliferator-Activated Receptors、Adipose Tissue and Metabolism、Metabolism, Diabetes, and Cancer

The nuclear receptor, peroxisome proliferatora c t ivated receptor( P PA R ), is an important regulator of adipocyte differentiation and a modulator of intracellular insulin-signaling events (1). PPA R mRNA expression in both skeletal muscle and adipose tissue in vitro is induced by insulin (2,3). In skeletal muscle of obese subjects, PPA R mRNA is elevated in direct relation to BMI and fasting insulinemia (2); reports are mixed as to whether expression is increased in adipose tissue of obese subjects (3–5). In one report, activators of PPA R were shown to increase adiposity in a rodent model (6), while in another (7) they were found to increase the number of adipocytes, but not the mass of adipose tissue. Clinically, most studies have not found that PPA R –activating thiazolidinediones cause weight gain when administered to humans for treatment of diabetes (1). Alternate use of promoters and differential splicing of the human PPARgene results in two isoforms: PPAR1 and PPAR2. PPAR2 contains 28 additional amino acids at its NH2 terminus (1,8). PPAR1 and PPAR2 both are expressed in adipose tissue (1,3–5), and there appears to be no difference in the abilities of the two isoforms to participate in ligand-induced initiation of transcription of target genes or in ligand-induced adipocyte differentiation (9). Interestingly, however, it was demonstrated recently that P PA R could activate transcription in a ligand-independent fashion and that insulin potentiated this activity (9). ...