Serum concentrations and gene expression of sirtuin 1 in healthy and slightly overweight subjects after caloric restriction or resveratrol supplementation: A randomized trial ☆ Antonio P. Mansur ⁎ ,1 , Alessandra Roggerio 1 , Marisa F.S. Goes 1 , Solange D. Avakian 1 , Dalila P. Leal 1 , Raul C. Maranhão 1 , Célia M.C. Strunz 1 Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil abstract article info Article history: Received 29 July 2016 Received in revised form 17 October 2016 Accepted 22 October 2016 Available online 27 October 2016 Background: Sirtuin 1 (Sirt1) plays an important role in vascular biology, and influences aspects of age-dependent atherosclerosis. In animals, the sirtuin system is strongly influenced by resveratrol and caloric restriction, but its expression in humans is controversial. This study investigated the effects of resveratrol and caloric restriction on Sirt1 serum concentrations and vascular biomarkers in a healthy human population. Methods and results: Forty-eight healthy participants (24 women) aged 55–65 years were randomized to either 30 days of resveratrol administration (500 mg/day) or caloric restriction (1000 cal/day). Blood was collected at baseline and day 30. Laboratory data analyzed were triglycerides, total cholesterol, HDL, VLDL, LDL, apolipopro- tein A1, apolipoprotein B, lipoprotein (a), non-esterified fatty acids (NEFA), glucose, insulin, oxidative stress, C-reactive protein, and Sirt1. Expression of the Sirt1 gene was analyzed using real-time PCR. Caloric restriction diminished the abdominal circumference and improved the lipid profile, but not resveratrol intervention. Resver- atrol and caloric restriction increased serum concentrations of Sirt1, from 1.06 ± 0.71 to 5.75 ± 2.98 ng/mL; p b 0.0001, and from 1.65 ± 1.81 to 5.80 ± 2.23 ng/mL; p b 0.0001, respectively. Sirt1 increased in women and men in both interventions. On the other hand expression of Sirt1 mRNA was not different after caloric restric- tion and resveratrol treatment. Conclusions: Caloric restriction and resveratrol significantly increased plasma concentrations of Sirt1. The long- term impact of these interventions on atherosclerosis should be assessed. © 2016 Elsevier Ireland Ltd. All rights reserved. Keywords: Sirtuin 1 Caloric restriction Resveratrol Gene expression Human population 1. Introduction The sirtuin system plays an important role in vascular biology and regulates aspects of longevity and age-dependent atherosclerosis [1–3]. Sirtuins are present in all body tissues. They are characterized by seven isoforms (sirtuin 1 to sirtuin 7) that are distributed in the cytoplasm, nucleus, and mitochondria of cells. Sirtuin 1 (Sirt1) predominates in the nucleus and cytoplasm of mammalian cellular compartments [4]. Sirt1 promotes the enzymatic reaction of NAD- dependent lysine deacetylation of various proteins forming nicotinic derivatives [5]. These nicotinic derivatives activate oxidative stress in cells by protecting the body from the harmful effects of metabolic end-products [6]. Among the isoforms, Sirt1 is the most studied and its pleiotropic functions are associated with protection from metabolic and chronic degenerative diseases [7,8]. Caloric restriction and resveratrol are two classical interventions that activate the sirtuin system in animal studies [9,10]. Caloric restric- tion is associated with longevity in small animals, and this effect is par- tially mediated by the sirtuin system [11]. Resveratrol is a natural polyphenol compound found in small amounts in grapes and wine. This compound mimics the effects of caloric restriction by activating the sirtuin system [12]. Animal studies have shown that caloric restric- tion interventions and administration of resveratrol increases serum concentrations and gene expression of Sirt1, and is associated with bet- ter metabolic profiles, better neuronal functions and anti-inflammatory activities [13]. Through specific metabolic pathways, these interven- tions are also associated with the best vascular homeostasis and protec- tion of endothelial senescence [14], reduced proliferation of vascular smooth muscle [15], DNA protection of vascular smooth muscle cells [16], reduced vascular tone by activating the enzymatic activity of nitric oxide [17], increased reverse cholesterol transport [18], and reducing insulin resistance [19,20]. International Journal of Cardiology 227 (2017) 788–794 ☆ Grant support: The São Paulo Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo) supported this study (No. 12/01,051–5). ⁎ Corresponding author at: Av. Dr. Enéas C. Aguiar, 44, CEP: 05403-000, São Paulo, Brazil. E-mail address: apmansur@usp.br (A.P. Mansur). 1 These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. http://dx.doi.org/10.1016/j.ijcard.2016.10.058 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved. Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard