Kolehmainen M, Uusitupa M I J, Alhava E, Laakso M, Vidal H
Department of Clinical Nutrition and Food and Health Research Center, University of Kuopio, Finland.
J Clin Endocrinol Metab. 2003 Apr;88(4):1717-22. doi: 10.1210/jc.2002-020603.
The aim was to study the effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR) gamma2 gene on the expression of PPARgamma 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 PPARgamma1, PPARgamma2, lipoprotein lipase, p85alpha 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 p85alpha 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 PPARgamma2 expression was higher in men with Ala12 allele (P < 0.01). Interestingly, particularly in women, the expression of both PPARgamma splice variants was lower in omental than sc fat independently of the genotype (P < 0.05-0.01). The common Pro12Ala polymorphism of the PPARgamma2 gene has minor influence on mRNA expression of PPARgamma target genes in adipose tissue of obese subjects. Expression of both PPARgamma splice variants is dependent on fat depot: omental fat shows lower mRNA levels, compared with sc fat depots.
目的是研究过氧化物酶体增殖物激活受体（PPAR）γ2基因的Pro12Ala多态性对脂肪组织中PPARγ靶基因表达的影响。从30名极度肥胖受试者（10名男性和20名女性）的网膜、腹部皮下和股部脂肪库采集脂肪组织样本。通过逆转录竞争PCR定量PPARγ1、PPARγ2、脂蛋白脂肪酶、p85α磷脂酰肌醇3激酶和解偶联蛋白2的mRNA表达。通过单链构象多态性分析确定Pro12Ala多态性的基因型。Ala12等位基因的频率为13.3%（8例Pro12Ala和22例Pro12Pro）。不同基因型之间的体重、脂肪量和空腹血清瘦素无差异。Pro12Ala携带者网膜脂肪中p85α磷脂酰肌醇3激酶的mRNA表达显著低于Pro12Pro携带者（P<0.01）。Ala12等位基因的男性中PPARγ2表达似乎也较高（P<0.01）。有趣的是，特别是在女性中，无论基因型如何，网膜脂肪中PPARγ两种剪接变体的表达均低于腹部皮下脂肪（P<0.05-0.01）。PPARγ2基因常见的Pro12Ala多态性对肥胖受试者脂肪组织中PPARγ靶基因的mRNA表达影响较小。PPARγ两种剪接变体的表达均取决于脂肪库：与腹部皮下脂肪库相比，网膜脂肪的mRNA水平较低。
