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Effect of the Pro12Ala Polymorphism in the Peroxisome Proliferator-Activated Receptor (PPAR) 2 Gene on the Expression of PPAR Target Genes in Adipose Tissue of Massively Obese Subjects

Department of Clinical Nutrition and Food and Health Research Center (M.K., M.I.J.U.), University of Kuopio, FIN-70211 Kuopio, Finland; Departments of Surgery (E.A.) and Internal Medicine (M.L.), Kuopio University Hospital, Kuopio, Finland; and Institut National de la Santé et de la Recherche Médicale U449 (H.V.), Faculté de Médecine R.Laennec, 69372 Lyon Cedex 08, France

Address all correspondence and requests for reprints to: Marjukka Kolehmainen, M.D., Department of Clinical Nutrition, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. E-mail: marjukka.kolehmainen{at}uku.fi.

The aim was to study the effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR) 2 gene on the expression of PPAR 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 PPAR1, PPAR2, lipoprotein lipase, p85 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 p85 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 PPAR2 expression was higher in men with Ala12 allele (P < 0.01). Interestingly, particularly in women, the expression of both PPAR splice variants was lower in omental than sc fat independently of the genotype (P < 0.05–0.01). The common Pro12Ala polymorphism of the PPAR2 gene has minor influence on mRNA expression of PPAR target genes in adipose tissue of obese subjects. Expression of both PPAR splice variants is dependent on fat depot: omental fat shows lower mRNA levels, compared with sc fat depots.

This work was supported by grants from the Academy of Finland; Research Council for Health; Jenny and Antti Wihuri Foundation, Finland; and Saastamoinen Foundation, Kuopio, Finland.

Abbreviations: BMI, Body mass index; LPL, lipoprotein lipase; OGTT, oral glucose tolerance test; PI3K, p85 regulatory subunit of phosphatidylinositol-3 kinase; PPAR, peroxisome proliferator-activated receptor; PPRE, PPAR-responsive element; RT, reverse transcription; RT-cPCR, reverse transcription-competitive PCR; UCP, uncoupling protein.

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