Administration of Low-dose Resveratrol Attenuated Hepatic Inflammation and Lipid Accumulation in High Cholesterol-fructose Diet-induced Rat Model of Nonalcoholic Fatty Liver Disease

Chih-Chun Chang ； Chieh-Yu Chang ； Pei-Chun Lin ； Jiung-Pang Huang ； Kuan-Hsing Chen ； Tzung-Hai Yen ； Li-Man Hung

《The Chinese Journal of Physiology》 63卷4期 (2020/08) Pp. 149-155

https://doi.org/10.4103/CJP.CJP_43_20

摘要

Resveratrol (RSV) has been demonstrated to ameliorate nonalcoholic fatty liver disease (NAFLD) in animal studies. However, RSV was given with the dosage that ranged from 7 to 300 mg/kg body weight (BW). Hence, the study aimed to investigate the efficacy of RSV at a lower dosage on high cholesterol-fructose diet (HCFD)-induced rat model of NAFLD. In the study, male Sprague-Dawley rats were fed with HCFD for 15 weeks. RSV was also given at a daily dose of 1 mg/kg BW for 15 days or 15 weeks by oral delivery. At sacrifice, plasma and liver specimens were acquired for detections of alanine and aspartate aminotransferases, proinflammatory cytokines, and lipid contents. Histological examinations and Western blotting analysis were performed using liver tissues. The results showed that RSV administration reduced plasma levels of aminotransferases and proinflammatory cytokines including interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) in HCFD-induced NAFLD. RSV also mitigated hepatic lipid accumulation and expression of IL-1β, IL-6, and TNF-α. Besides, phosphorylation of signal transducer and activator of transcription 3 (STAT3) was reduced with RSV supplementation in the liver of HCFD-fed rats. We concluded that low-dose RSV supplementation attenuated hepatic inflammation and lipid accumulation in HCFD-induced NAFLD. The ameliorative effect of RSV on NAFLD could be associated with downregulation of phosphorylated STAT3.

關鍵字

High cholesterol-fructose diet ； inflammation ； interleukin ； nonalcoholic fatty liver disease ； resveratrol ； STAT3

參考文獻

Lazo M, Hernaez R, Eberhardt MS, Bonekamp S, Kamel I, Guallar E, et al. Prevalence of nonalcoholic fatty liver disease in the United States: The Third National Health and Nutrition Examination Survey, 1988-1994. Am J Epidemiol 2013;178:38-45.

Ahmed A, Wong RJ, Harrison SA. Nonalcoholic fatty liver disease review: Diagnosis, treatment, and outcomes. Clin Gastroenterol Hepatol 2015;13:2062-70.

Younossi ZM, Stepanova M, Afendy M, Fang Y, Younossi Y, Mir H, et al. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol 2011;9:524-300.

Machado MV, Diehl AM. Pathogenesis of nonalcoholic steatohepatitis. Gastroenterology 2016;150:1769-77.

Nasr P, Ignatova S, Kechagias S, Ekstedt M. Natural history of nonalcoholic fatty liver disease: A prospective follow-up study with serial biopsies. Hepatol Commun 2018;2:199-210.