The therapeutic effects of resveratrol on hepatic steatosis in high-fat diet-induced obese mice by improving oxidative stress, inflammation and lipid-related gene transcriptional expression
So far, the majority of the previous animal studies have focused on the preventive effects of resveratrol (RSV) on non-alcoholic fatty liver disease (NAFLD) rather than the therapeutic effects. In this study, the therapeutic effects of RSV on hepatic oxidative stress (OS), inflammation, and lipid metabolism-related gene expression of obese mice induced by a high-fat diet (HFD) were investigated. Male C57BL/6 mice were fed a HFD for 8 weeks to induce obesity-related NAFLD model. And then, NAFLD mice were treated with daily RSV oral gavage at the dose of 100 mg/kg body weight for an additional 4 weeks. HFD-induced the elevation of serum total cholesterol, high-density lipoprotein cholesterol, glucose, insulin, aspartate aminotransferase and alanine aminotransferase levels, and homeostasis model assessment of insulin resistance, hepatic histology changes, the increases in hepatic triglyceride, malondialdehyde and tumor necrosis factor alpha concentrations, as well as the higher mRNA expression of hepatic toll-like receptor 4 and cluster of differentiation 36 in mice, were restored by RSV. The therapeutic effects of RSV against hepatic steatosis of HFD obese mice were attributed to the reduction of OS, inflammation and free fatty acid uptake.
KeywordsResveratrol Hepatic steatosis Oxidative stress Inflammation Lipid metabolism Obesity
This work was supported by the National Natural Science Foundation of China (Grant nos. 31772634, 31802094 and 31601948), the National Key Research and Development Program of China (Grant no. 2018YFD0501101), the Postdoctoral Research Foundation of China (Grant no. 2018M632320), the Natural Science Foundation of Jiangsu Province (Grant no. BK20180531), and the Open Project of Shanghai Key Laboratory of Veterinary Biotechnology (Grant no. klab201710).
Compliance with ethical standards
Conflict of interest
The authors declare that there are no conflicts of interests.
- 3.Williamson RM, Price JF, Glancy S, Perry E, Nee LD, Hayes PC, Frier BM, Van Look LA, Johnston GI, Reynolds RM (2011) Prevalence of and risk factors for hepatic steatosis and nonalcoholic fatty liver disease in people with type 2 diabetes: the edinburgh type 2 diabetes study. Diabetes Care 34:1139–1144CrossRefGoogle Scholar
- 7.Allen L, Ramalingam L, Menikdiwela K, Scoggin S, Shen CL, Tomison MD, Kaur G, Dufour JM, Chung E, Kalupahana NS, Moustaid-Moussa N (2017) Effects of delta-tocotrienol on obesity-related adipocyte hypertrophy, inflammation and hepatic steatosis in high-fat-fed mice. J Nutr Biochem 48:128–137CrossRefGoogle Scholar
- 12.Labbé A, Garand C, Cogger VC, Paquet ER, Desbiens M, Le CD, Lebel M (2011) Resveratrol improves insulin resistance hyperglycemia and hepatosteatosis but not hypertriglyceridemia, inflammation, and life span in a mouse model for Werner syndrome. J Gerontol A Biol Sci Med Sci 66:264–278CrossRefGoogle Scholar
- 23.Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509Google Scholar
- 25.Cheng K, Song ZH, Zheng XC, Zhang H, Zhang JF, Zhang LL, Zhou YM, Wang T (2017) Effects of dietary vitamin E type on the growth performance and antioxidant capacity in cyclophosphamide immunosuppressed broilers. Poult Sci 96:1159–1166Google Scholar
- 26.Cheng K, Niu Y, Zheng XC, Zhang H, Chen YP, Zhang M, Huang XX, Zhang LL, Zhou YM, Wang T (2016) A comparison of natural (D-α-tocopherol) and synthetic (DL-α-tocopherol acetate) vitamin E supplementation on the growth performance, meat quality and oxidative status of broilers. Asian-Australas J Anim Sci 29:681–688CrossRefGoogle Scholar
- 33.Jiang M, Li X, Yu X, Liu X, Xu X, He J, Gu H, Liu L (2017) Oral administration of resveratrol alleviates osteoarthritis pathology in C57BL/6J mice model induced by a high-fat diet. Mediators Inflamm 2017:7659023Google Scholar
- 34.Yu S, Matsusue K, Kashireddy P, Cao WQ, Yeldandi V, Yeldandi AV, Rao MS, Gonzalez FJ, Reddy JK (2003) Adipocyte-specific gene expression and adipogenic steatosis in the mouse liver due to peroxisome proliferator-activated receptor gamma1 (PPARgamma1) overexpression. J Biol Chem 278:498–505CrossRefGoogle Scholar