Lentivirus-mediated Sirt1 shRNA and resveratrol independently induce porcine preadipocyte apoptosis by canonical apoptotic pathway

Abstract

The effects of Sirt1 gene and resveratrol on porcine preadipocyte apoptosis have not been characterized. Here, we investigated the apoptotic effects of Sirt1 and resveratrol on porcine preadipocytes, finding that resveratrol-induced preadipocyte apoptosis and up-regulated protein levels of Sirt1. Intriguingly, Sirt1 knockdown by RNAi also resulted in preadipocyte apoptosis. Combining resveratrol treatment and Sirt1 knockdown has an additive effect to promote porcine preadipocyte death. We found that resveratrol treatment alone dose-dependently increased caspase-3 cleavage, as well as the levels of Bax, p53 and acetylated-p53. Interestingly, the ratio of acetylated-p53 over p53 was declined owing to deacetylation by increased Sirt1 expression. Down-regulation of Sirt1 also elevated the cleavage of caspase-3 with a decrease of p53 acetylation. These data indicate that although resveratrol treatment up-regulates Sirt1 expression, it augments porcine preadipocyte apoptosis in a Sirt1-independent manner. The regulation of apoptosis by resveratrol and Sirt1 may provide a novel insight to control preadipocyte number through cellular apoptosis.