Effect of the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor (PPAR) γ2 gene on the expression of PPARγ target genes in adipose tissue of massively obese subjects

Abstract

The aim was to study the effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR) γ2 gene on the expression of PPARγ target genes in adipose tissue. Adipose tissue samples were collected from 30 massively obese subjects (10 men and 20 women) from omental, sc abdominal, and femoral depots. The mRNA expression of PPARγ1, PPARγ2, lipoprotein Upase, p85α phosphatidylinositol 3-kinase, and uncoupling protein 2 were quantified by reverse transcription-competitive PCR. The genotypes of Pro12Ala polymorphism were determined by single-strand conformation polymorphism analysis. The frequency of the Ala12 allele was 13.3% (8 Pro12Ala and 22 Pro12Pro). There were no differences in body weight, fat mass, and fasting serum leptin between the genotypes. The mRNA expression of p85α phosphatidylinositol 3-kinase was significantly lower in the omental fat of the Pro12Ala carriers than the Pro12Pro carriers (P < 0.01). It also appeared that PPARγ2 expression was higher in men with Ala12 allele (P < 0.01). Interestingly, particularly in women, the expression of both PPARγ splice variants was lower in omental than sc fat independently of the genotype (P < 0.05-0.01). The common Pro12Ala polymorphism of the PPARγ2 gene has minor influence on mRNA expression of PPARγ target genes in adipose tissue of obese subjects. Expression of both PPARγ splice variants is dependent on fat depot: omental fat shows lower mRNA levels, compared with sc fat depots.