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Resveratrol Activates Sirtuin-1 and Mediates Epigenetic Patterns in Diabetes

3/6/2018 1:04:36 PM
Sirtuin-1 (SIRT-1) is a NAD-dependent protein involved in the deacetylation of histones and nonhistone proteins, including p53 and H3K56. Downregulation of SIRT-1 contributes to increased p53 acetylation and accumulation of reactive oxygen species—an epigenetic pattern that has been linked to the metabolic changes of type 2 diabetes. High levels of H3K56 acetylation are also an epigenetic marker of oxidative stress and associated with diabetes-related genes, but it is not known to what extent downregulation of SIRT-1 might contribute to H3K56 acetylation and metabolic dysfunction in type 2 diabetes.
Resveratrol is one of the most potent known activators of SIRT-1 expression. Researchers aimed to determine whether resveratrol supplementation would rescue SIRT-1 activity, deacetylate H3K56, and reduce oxidative stress in patients with type 2 diabetes. A total of 192 patients with type 2 diabetes were randomized to take resveratrol (500mg/d or 40mg/d) or placebo for 6 months. Resveratrol was standardized to 98-99% trans-resveratrol purity. At baseline and 6-months, peripheral blood mononuclear cells (PBMCs) were used to evaluate SIRT-1 expression and p53 and H3K56 acetylation.
A significant, dose-dependent increase in SIRT-1 expression was found after resveratrol supplementation. Surprisingly, however, not all patients taking resveratrol showed an increase in SIRT-1. Patients who experienced the greatest increase in SIRT-1 expression displayed a significant decrease in H3K56 acetylation, no significant change in p53 expression, a significant increase in total antioxidant status (TAS) values, and a significant decrease in percent body fat.    
The results of this study show that boosting SIRT-1 expression translates into epigenetic changes that reduce H3K56 acetylation and improve antioxidant activity in patients with type 2 diabetes.
Bo S, Togliatto G, Gambino R et al. Impact of sirtuin-1 expression on H3K56 acetylation and oxidative stress: a double-blind randomized controlled trial with resveratrol supplementation. Acta Diabetol. 2018