Dataset Information

Resveratrol Inhibits Neointimal Growth after Arterial Injury in High-Fat-Fed Rodents: The Roles of SIRT1 and AMPK.

ABSTRACT: We have shown that both insulin and resveratrol (RSV) decrease neointimal hyperplasia in chow-fed rodents via mechanisms that are in part overlapping and involve the activation of endothelial nitric oxide synthase (eNOS). However, this vasculoprotective effect of insulin is abolished in high-fat-fed insulin-resistant rats. Since RSV, in addition to increasing insulin sensitivity, can activate eNOS via pathways that are independent of insulin signaling, such as the activation of sirtuin 1 (SIRT1) and AMP-activated kinase (AMPK), we speculated that unlike insulin, the vasculoprotective effect of RSV would be retained in high-fat-fed rats. We found that high-fat feeding decreased insulin sensitivity and increased neointimal area and that RSV improved insulin sensitivity (p < 0.05) and decreased neointimal area in high-fat-fed rats (p < 0.05). We investigated the role of SIRT1 in the effect of RSV using two genetic mouse models. We found that RSV decreased neointimal area in high-fat-fed wild-type mice (p < 0.05), an effect that was retained in mice with catalytically inactive SIRT1 (p < 0.05) and in heterozygous SIRT1-null mice. In contrast, the effect of RSV was abolished in AMKP?2-null mice. Thus, RSV decreased neointimal hyperplasia after arterial injury in both high-fat-fed rats and mice, an effect likely not mediated by SIRT1 but by AMPK?2.

SUBMITTER: Guo J

PROVIDER: S-EPMC7845450 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Resveratrol Inhibits Neointimal Growth after Arterial Injury in High-Fat-Fed Rodents: The Roles of SIRT1 and AMPK.

Guo June J Pereira Troy J TJ Mori Yusaku Y Gonzalez Medina Marel M Breen Danna M DM Dalvi Prasad S PS Zhang Hangjun H McCole Declan F DF McBurney Michael W MW Heximer Scott P SP Tsiani Evangelia L EL Dolinsky Vernon W VW Giacca Adria A

Journal of vascular research 20200810 6

We have shown that both insulin and resveratrol (RSV) decrease neointimal hyperplasia in chow-fed rodents via mechanisms that are in part overlapping and involve the activation of endothelial nitric oxide synthase (eNOS). However, this vasculoprotective effect of insulin is abolished in high-fat-fed insulin-resistant rats. Since RSV, in addition to increasing insulin sensitivity, can activate eNOS via pathways that are independent of insulin signaling, such as the activation of sirtuin 1 (SIRT1) ...[more]

PMID: 32777783

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Project description:Studies have demonstrated that resveratrol (a natural polyphenol) and caloric restriction activate Sirtuin-1 (SIRT1) and induce autophagy. Furthermore, autophagy is induced by the SIRT1-FoxO signaling pathway and was recently shown to be a critical protective mechanism against non-alcoholic fatty liver disease (NAFLD) development. We aimed to compare the effects of resveratrol and caloric restriction on hepatic lipid metabolism and elucidate the mechanism by which resveratrol supplementation and caloric restriction alleviate hepatosteatosis by examining the molecular interplay between SIRT1 and autophagy.Eight-week-old male Wistar rats (40) were divided into four groups: the STD group, which was fed a standard chow diet; the HFD group, which was fed a high-fat diet; HFD-RES group, which was fed a high-fat diet plus resveratrol (200 mg/kg.bw); and the HFD-CR group, which was fed a high-fat diet in portions containing 70% of the mean intake of the HFD group rats. The groups were maintained for 18 weeks. Metabolic parameters, Oil Red O and hematoxylin-eosin staining of the liver, and the mRNA and protein expression of SIRT1, autophagy markers and endoplasmic reticulum(ER) stress-associated genes in the liver were assessed after the 18-week treatment. We found that resveratrol (200 mg/kg bw) and caloric restriction (30%) partially prevented hepatic steatosis and hepatocyte ballooning, increased the expression of SIRT1 and autophagy markers while decreasing ER stress markers in the liver and alleviated lipid metabolism disorder. Moreover, caloric restriction provided superior protection against HFD-induced hepatic fatty accumulation compared with resveratrol and the effects were associated with decreased total energy intake and body weight.We conclude that the SIRT1-autophagy pathway and decreased ER stress are universally required for the protective effects of moderate caloric restriction (30%) and resveratrol (a pharmacological SIRT1 activator) supplementation against HFD-induced hepatic steatosis.

Project description:This study investigated the effects of resveratrol on the growth performance, energy sensing, glycolipid metabolism and glucose and insulin load of blunt snout bream Megalobrama amblycephala fed high-carbohydrate diets. Fish (39.44 ± 0.06 g) were randomly fed three diets: a control diet (30% carbohydrate), a high-carbohydrate diet (HC, 41% carbohydrate), and the HC diet supplemented with 0.04% resveratrol (HCR) for 12 weeks. Fish fed the HC diet had significantly high values of nitrogen and energy retention efficiency, hepatosomatic index, intraperitoneal fat ratio, whole-body lipid content and intraperitoneal fat glycogen and lipid contents compared to the control group, but showed little difference with the HCR treatment. Liver and muscle lipid contents and plasma levels of glucose, glycated serum protein, advanced glycation end products and total cholesterol of fish fed the HC diet were significantly higher than those of the control group, whereas the opposite was found with resveratrol supplementation. Fish fed the HC diet obtained significantly low values of plasma insulin levels and hepatic adenosine monophosphate (AMP) contents and NAD+/NADH ratio compared to HCR treatment, but showed little difference with the control group. The opposite was found for hepatic adenosine triphosphate (ATP) contents and the ATP/AMP ratio. In addition, fish fed the HC diet showed significantly high transcriptions of glucose transporter 2 (GLUT2), glucose-6-phosphate dehydrogenase, glycogen synthase, fatty acid synthetase (FAS), acetyl-CoA carboxylase α (ACCα), peroxisome proliferator-activated receptor γ and PPARα compared to the control group, whereas the opposite was found for protein levels of AMP-activated protein kinase α (t-AMPKα), phosphorylated AMP-activated protein kinase α (p-AMPKα), sirtuin-1 (SIRT1), and p-AMPKα/t-AMPKα ratio as well as the transcriptions of AMPKα1, AMPKα2, SIRT1, PPARγ coactivator-1α (PGC-1α), phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase (FBPase), glucose-6-phosphatase, carnitine palmitoyl transferase I (CPT I) and acyl-CoA oxidase. Resveratrol supplementation significantly up-regulated the protein levels of t-AMPK, p-AMPK, and SIRT1, p-AMPK/t-AMPK ratio as well as the transcriptions of AMPKα1, AMPKα2, SIRT1, PGC-1α, GLUT2, FBPase, and CPT I compared to HC group, while the opposite was found for sterol regulatory element-binding protein-1, FAS and ACCα. Furthermore, resveratrol improved glucose and insulin tolerance of fish fed the HC diet after glucose and insulin load.

Dataset Information

Resveratrol Inhibits Neointimal Growth after Arterial Injury in High-Fat-Fed Rodents: The Roles of SIRT1 and AMPK.

Publications

Resveratrol Inhibits Neointimal Growth after Arterial Injury in High-Fat-Fed Rodents: The Roles of SIRT1 and AMPK.

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