SIRT1 induction in the skeletal muscle of male mice partially attenuates changes to whole-body metabolism in response to androgen deprivation

In males, androgens regulate whole body metabolism. The components in androgen target organs contributing to whole-body metabolic function remain ill defined. Sirtuin1 (SIRT1) protein levels are lower in the limb muscle of male mice subjected to androgen deprivation. Because SIRT1 can influence whole-body metabolism, the purpose was to assess whether muscle specific SIRT1 induction attenuated changes to whole-body metabolism in response to androgen deprivation. Physically mature male mice containing an inducible muscle specific SIRT1 transgene (SIRT1) were subjected to a sham or castration surgery and compared to sham and castrated male mice where the SIRT1 transgene was not induced (WT). The respiratory exchange ratio (RER), energy expenditure, and carbohydrate and fat oxidation rates were determined using metabolic cages. Castration lowered RER in WT mice and the lower RER coincided with lower energy expenditure, lower carbohydrate oxidation rates, and higher fat oxidation rates. SIRT1 induction attenuated the castration-induced changes to RER and fat oxidation rates. Changes to energy expenditure and glucose oxidation rates were not affected by SIRT1. Decreases in muscle SIRT1 protein in males may partially contribute to the dysregulation of whole-body metabolism in response to androgen deprivation.