PMID- 29330620 OWN - NLM STAT- MEDLINE DCOM- 20180524 LR - 20220321 IS - 1432-5233 (Electronic) IS - 0940-5429 (Print) IS - 0940-5429 (Linking) VI - 55 IP - 4 DP - 2018 Apr TI - Impact of sirtuin-1 expression on H3K56 acetylation and oxidative stress: a double-blind randomized controlled trial with resveratrol supplementation. PG - 331-340 LID - 10.1007/s00592-017-1097-4 [doi] AB - AIMS: Sirtuin-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 RESULTS: At 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). CONCLUSIONS: We 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. FAU - Bo, Simona AU - Bo S AD - Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy. FAU - Togliatto, Gabriele AU - Togliatto G AD - Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy. FAU - Gambino, Roberto AU - Gambino R AD - Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy. FAU - Ponzo, Valentina AU - Ponzo V AD - Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy. FAU - Lombardo, Giusy AU - Lombardo G AD - Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy. FAU - Rosato, Rosalba AU - Rosato R AD - Department of Psychology, University of Turin, Turin, Italy. FAU - Cassader, Maurizio AU - Cassader M AD - Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy. FAU - Brizzi, Maria Felice AU - Brizzi MF AUID- ORCID: 0000-0003-0944-6992 AD - Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy. mariafelice.brizzi@unito.it. LA - eng SI - ClinicalTrials.gov/NCT02244879 PT - Journal Article PT - Observational Study PT - Randomized Controlled Trial DEP - 20180112 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Antioxidants) RN - 0 (Histones) RN - 0 (Stilbenes) RN - EC 3.5.1.- (Sirtuin 1) RN - Q369O8926L (Resveratrol) SB - IM MH - Acetylation/drug effects MH - Adult MH - Aged MH - Antioxidants/*pharmacology MH - Diabetes Mellitus, Type 2/blood/*drug therapy/*metabolism MH - Dietary Supplements MH - Double-Blind Method MH - Down-Regulation MH - Female MH - Histones/*metabolism MH - Humans MH - Leukocytes, Mononuclear/drug effects/metabolism MH - Male MH - Middle Aged MH - Oxidative Stress/drug effects/*physiology MH - Resveratrol MH - Sirtuin 1/*metabolism MH - Stilbenes/administration & dosage/*pharmacology PMC - PMC5851693 OTO - NOTNLM OT - Epigenetics OT - PBMC OT - Resveratrol OT - Sirtuin-1 COIS- CONFLICTS OF INTEREST: The authors report no conflict of interest. ETHICAL APPROVAL: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. INFORMED CONSENT: Informed consent was obtained from all individual participants included in the study. EDAT- 2018/01/14 06:00 MHDA- 2018/05/25 06:00 PMCR- 2018/01/12 CRDT- 2018/01/14 06:00 PHST- 2017/11/13 00:00 [received] PHST- 2017/12/29 00:00 [accepted] PHST- 2018/01/14 06:00 [pubmed] PHST- 2018/05/25 06:00 [medline] PHST- 2018/01/14 06:00 [entrez] PHST- 2018/01/12 00:00 [pmc-release] AID - 10.1007/s00592-017-1097-4 [pii] AID - 1097 [pii] AID - 10.1007/s00592-017-1097-4 [doi] PST - ppublish SO - Acta Diabetol. 2018 Apr;55(4):331-340. doi: 10.1007/s00592-017-1097-4. Epub 2018 Jan 12.