Resveratrol improves high-fat diet induced insulin resistance by rebalancing subsarcolemmal mitochondrial oxidation and antioxidantion

Abstract

Although resveratrol (RES) is thought to be a key regulator of insulin sensitivity in rodents, the exact mechanism underlying this effect remains unclear. Therefore, we sought to investigate how RES affects skeletal muscle oxidative and antioxidant levels of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondrial populations in high-fat diet (HFD)-induced insulin resistance (IR) rats. Systemic and skeletal muscle insulin sensitivity together with expressions of several genes related to mitochondrial biogenesis and skeletal muscle SIRT1, SIRT3 protein levels were studied in rats fed a normal diet, a HFD, and a HFD with intervention of RES for 8 weeks. Oxidative stress levels and antioxidant enzyme activities were assessed in SS and IMF mitochondria. HFD fed rats exhibited obvious systemic and skeletal muscle IR as well as decreased SIRT1 and SIRT3 expressions, mitochondrial DNA (mtDNA), and mitochondrial biogenesis (p<0.05). Both SS and IMF mitochondria demonstrated elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels. In addition, SS mitochondrial antioxidant enzyme activities were significantly lower, while IMF mitochondrial antioxidant enzyme activities were higher (p<0.05). By contrast, RES treatment protected rats against diet induced IR, increased SIRT1 and SIRT3 expressions, mtDNA, and mitochondrial biogenesis (p<0.05). Moreover, the activities of SS and IMF mitochondrial antioxidant enzymes were increased, which reverted the increased SS mitochondrial oxidative stress levels (p<0.05). This study suggests that RES ameliorates insulin sensitivity consistent with improved SIRT3 expressions and rebalance between SS mitochondrial oxidative stress and antioxidant competence in HFD rats.

Caloric restriction, resveratrol and melatonin: Role of SIRT1 and implications for aging and related-diseases

“…In mice, resveratrol caused an activation of SIRT1, and its target PGC1-␣, which leads to changes in mitochondrial number and function (Lagouge et al, 2006). Resveratrol intervention also resulted in increased levels of SIRT1, PGC-1␣, and mtDNA copy number, and there was an improvement in high-fat diet-induced insulin resistance (Haohao et al, 2015). Recently it was reported that resveratrol can act as an anti-diabetic agent, due to the repression of the FOXO1 (an important player in insulin signaling) by activation of SIRT1 deacetylase (Sin et al, 2015).…”

Resveratrol ameliorates diabetic nephropathy in rats through negative regulation of the p38 MAPK/TGF-β1 pathway

“…Previous studies have demonstrated that RSV has diverse beneficial health effects including anti-oxidative (17), anti-inflammatory (18), anti-cancer (19), cardioprotective (20) and neuroprotective (21) activities. In relation to diabetic nephropathy, previous reports have indicated that RSV can ameliorate renal insufficiency and pathological changes, as well as prevent high glucose-induced mesangial cell proliferation and glomerular fibronectin expression though multiple signaling pathways under diabetic conditions both in vivo and in vitro .…”

Resveratrol-Loaded Solid Lipid Nanoparticle Supplementation Ameliorates Physical Fatigue by Improving Mitochondrial Quality Control

“…RSV has been widely explored because of the discovery of antioxidant effects [30]. RSV protects mitochondrial function and mass against stress-induced oxidative damage [31].…”