Resveratrol ameliorates hepatic metaflammation and inhibits NLRP3 inflammasome activation

Objective. Resveratrol (RSV) regulates NAD bioavailability and sirtuin-related metabolism, which relates to aging, metabolic syndrome and non-alcoholic fatty liver disease. The purpose of this study was to investigate the effects of resveratrol on hepatic metaflammation in a rodent model of high-fat (HF) diet-induced obesity (DIO). Materials/Methods. DIO was induced in a subset of mice given an HF diet (45% kcal fat). After 6 weeks of HF diet feeding, RSV was delivered via an osmotic pump for 4 weeks. The experimental groups were as follows: 1) lean control fed with a standard diet, 2) HF diet-induced obese control, and 3) HF_RSV (8 mg/kg/day). After 4 weeks of each treatment, blood and liver tissues were collected and the indices of glucose control, serum and liver triglyceride (TG), sirtuin pathway, inflammation, and NOD-like receptor family, pryin domain containing 3 (NLRP3) inflammasome were analyzed. Results. Body weight and food intake were not altered by administering resveratrol. Glucose control was impaired, and serum and liver TG levels were increased by the HF diet. Hepatic inflammation was aggravated in mice fed with the HF diet, as shown by the increased levels of the pro-inflammatory markers interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha in the liver. However, resveratrol administration significantly improved glucose control, and serum and liver TG contents. Also, resveratrol treatment reduced the levels of the pro-inflammatory markers. These improvements were accompanied by alterations in sirtuin pathway and NLRP3 inflammasome activation. Conclusion. These results demonstrate that resveratrol ameliorates hepatic metaflammation, accompanied by alterations in NLRP3 inflammasome. (C) 2014 Elsevier Inc. All rights reserved.