Impact of sirtuin-1 expression on H3K56 acetylation and oxidative stress: a double-blind randomized controlled trial with resveratrol supplementation

Abstract

AimsSirtuin-1 (SIRT-1) down-regulation in type 2 diabetes mellitus (T2DM) has been associated with epigenetic markers of oxidative stress. We herein aim to evaluate whether an increase in SIRT-1 expression affects histone 3 acetylation at the 56 lysine residue (H3K56ac) in T2DM patients randomly selected to receive either resveratrol (40 mg or 500 mg) or a placebo for 6 months. The primary outcome is changes in the H3K56ac level by variation in SIRT-1 expression and the secondary outcome is the evidence of association between SIRT-1 level, antioxidant markers (TAS), and metabolic variables.Methods and resultsAt baseline, peripheral blood mononuclear cell H3K56ac values among the SIRT-1 tertiles did not differ. At trial end, SIRT-1 levels were significantly higher in patients receiving 500 mg resveratrol. At follow-up, patients were divided into tertiles of delta (trial end minus baseline) SIRT-1 value. Significant reductions in H3K56ac and body fat percentage were found in the highest tertile as were increased TAS levels. A multiple logistic regression model showed that the highest delta SIRT-1 tertile was inversely associated with variations in H3K56ac (OR = 0.66; 95% CI 0.44–0.99), TAS (OR = 1.01; 95% CI 1.00–1.02), and body fat percentage (OR = 0.75; 95% CI 0.58–0.96). ConclusionsWe provide new knowledge on H3K56ac and SIRT-1 association in T2DM. These data suggest that boosting SIRT-1 expression/activation may impact redox homeostasis in these patients.ClinicalTrials.gov Identifier NCT02244879.

Sirtuins and diabetes: optimizing the sweetness in the blood

“…It has been observed boosting sirt1 expression through resveratrol treatment led to lower levels of H3K56Ac and also decreased body fat percentage ( Fig. 2) [25]. This study described the inverse relationship between the sirt1 expression with H3K56Ac levels.…”

Green cardamom increases Sirtuin-1 and reduces inflammation in overweight or obese patients with non-alcoholic fatty liver disease: a double-blind randomized placebo-controlled clinical trial

“…Serum level of Sirt1 was measured in this study. Sirt1 was primarily represented as a nuclear protein [ 57 ] and leukocytes (peripheral blood mononuclear cell [PBMC]) have been used for determining Sirt1 expression [ 58 ]. However, it was demonstrated that Sirt1 moves between the nucleus and cytoplasm.…”

Oxidative stress: role of physical exercise and antioxidant nutraceuticals in adulthood and aging

“…SIRTs are a family of NAD + dependent histone/protein deacetylases highly conserved through bacteria and eukaryotes [ 111 ]. SIRT1 has been demonstrated to inhibit oxidative stress and inflammation [ 112 , 113 ] and deacetylates a wide range of substrates, including p53, NF-κB, FOXO transcription factors, Ku-70 and PGC-1 α, with roles in cellular processes ranging from energy metabolism to cell survival. Many studies in recent years have highlighted the correlation of SIRT1 activity with AMPK and mTOR pathway [ 114 – 116 ].…”