Genistein, daidzein, and resveratrols stimulate PGC-1β-mediated gene expression

PGC-1β is a transcriptional co-activator of nuclear receptors such as the estrogen receptor-related receptor (ERR). Transgenic overexpression of PGC-1β in mice increases energy expenditure and suppresses high-fat diet-induced obesity. In this study, we screened various food-derived and natural compounds using a reporter assay system to measure the transcriptional activity of PGC-1β. Soy-derived isoflavones, genistein and daidzein, and several resveratrols activated PGC-1β. Genistein, daidzein, and trans-oxyresveratrol activated ERR-responsive element-mediated reporter activity in the presence of PGC-1β. Stable overexpression of PGC-1β in C2C12 myoblasts increased the expression of medium-chain acyl-CoA dehydrogenase (MCAD), an important enzyme in fatty acid β-oxidation. Genistein and daidzein increased MCAD mRNA levels and mitochondrial content in PGC-1β-expressing C2C12 cells. These compounds activated ERR/PGC-1β complex-mediated gene expression, and our findings may be a practical foundation for developing functional foods targeting obesity.