Resveratrol activates sirtuin-1 and mediates epigenetic patterns in diabetes

Published: 16-Mar-2018

Sirtuin-1 (SIRT-1) is a NAD-dependent protein involved in the deacetylation of histones and non-histone 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 randomised to take resveratrol (500 mg/d or 40 mg/d) or a placebo for 6 months.

Resveratrol was standardised 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 percentage 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.

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