Sir2 is essential for intergenerational effects of parental diet on offspring metabolism in Drosophila

Abstract

Recent studies have revealed that parental diet can affect offspring metabolism and longevity in Drosophila. However, the underlying mechanisms are still unknown. Here we demonstrate that Sir2 encoding an NAD+-dependent histone deacetylase is required for the intergenerational effects of low nutrition diet (1:5 dilution of standard diet). We observed an increased amount of triacylglyceride (TAG) in the offspring when fathers were maintained on a low nutrition diet for 2 days. The offspring had increased levels of metabolites of glycolysis and TCA cycle, the primary energy producing pathways. We found that Sir2 mutant fathers showed no intergenerational effects. RNAi-mediated knockdown of Sir2 in the fat body was sufficient to mimic the Sir2 mutant phenotype, and the phenotype was rescued by transgenic expression of wild-type Sir2 in the fat body. Interestingly, even fathers had no experience of low nutrition diet, overexpression of Sir2 in their fat bodies induced a high level of TAG in the offspring. These findings indicated that Sir2 is essential in the fat body of fathers to induce intergenerational effects of low nutrition diet.