Eicosapentaenoic acid induces mRNA expression of peroxisome proliferator-activated receptor gamma.

Abstract

To verify whether polyunsaturated fatty acids (PUFAs) can regulate the expression of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) in human adipose tissue. The effect of various PUFAS on PPARgamma1 and -gamma2 mRNA expression was investigated in freshly isolated adipocytes prepared from fat samples obtained during surgery. PPARgamma mRNA levels were also determined in subcutaneous adipose tissue biopsies of 11 obese women, in the fasting state, to search for in vivo associations between PPARgamma expression and plasma PUFA concentrations. PPARgamma mRNA levels were determined by reverse-transcription competitive polymerase chain reaction. Eicosapentaenoic acid (EPA) significantly increased PPARgamma1 mRNA levels in isolated adipocytes, without affecting the expression of PPARgamma2. The other tested fatty acids (linolenic acid, docosahexaenoic acid and omega-6 PUFAs) had no effect. The effect of EPA was dependent on the concentration (maximal effect after 6 hours with 50 microM) and was not reproduced by activators of the different members of the PPAR family. In addition, a strong positive correlation was found between plasma EPA concentrations and PPARgamma mRNA levels in adipose tissue of obese subjects. Our results demonstrate that adipose tissue PPARgamma1 mRNA concentration is positively regulated by EPA, suggesting that the composition of dietary lipids may affect PPARgamma gene expression in vivo in humans. These data also suggest that an induction of the expression of this nuclear receptor isoform might be involved in the mechanism of action of EPA and in some of its beneficial effects.