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Genistein Stimulates AMPK Phosphorylation and Expression of genes involved in fatty acid oxidation in skeletal muscle

Consumption of soy protein in rat models of OID and Zucker fa/fa increases the expression of genes involved with fatty acids oxidation as well as the phosphorylation of AMPK and ACC in skeletal muscle. The aim of this study was to determine whether soy isoflavones were partly responsible for the increase in gene expression of oxidative genes and phosphorylation of AMPK and ACC in skeletal muscle. With this purpose we injected rats intraperitoneally with either genistein or daidzein, and we observed in skeletal muscle a significant increase in the expression of CPT1, UCP3, PGC1α, PPARδ and SIRT1 as well as AMPK and ACC phosphorylation in skeletal muscle mainly with genistein. The increase in the expression of these genes and the AMPK and ACC phosphorylation was also observed when C2C12 cells were incubated with genistein. Interestingly, stimulation of C2C12 gene expression induced by the addition of genistein was partially repressed when cells were incubated with inhibitors of SIRT1 and PPARδ. These results indicate that genistein stimulates the expression of genes involved in fatty acid oxidation, possibly mediated via SIRT1 and PPARδ.