Resveratrol, a polyphenolic activator of the silent information regulation 2 homolog 1 (SIRT1), has been shown to extend the lifespan and improve metabolic disease. Other research has found that resveratrol inhibits ethanol-induced steatohepatitis in rats, due to its antioxidant properties. Steatohepatitis is liver disease characterized by inflammation with concurrent fat accumulation. Two of the negative consequences associated with the current obesity epidemic are development of hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). With this information in mind, Korean researchers investigated the possible beneficial effects of resveratrol on hepatic gene expression, lipid content, lipid profiles, and non-alcoholic steatohepatitis (NASH) on mice fed an atherogenic (Ath) diet (Ahn et al, 2008).
A mouse model was used by these researchers because it was suggested as a good model for studying human NASH. In the current research, mice were divided into three groups: control mice given a normal diet, mice fed an Ath diet, and mice fed an Ath diet containing resveratrol (Ath + RV diet). The mice were given the experimental diets (ad libitum) for eight weeks, free access to water and body weights were recorded weekly. Serum and tissue triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C) and free cholesterol (FC) levels were determined. Liver tissues were scored for hepatic steatosis and necroinflammation. Hepatic gene expression profiles were determined using microarray technology and real time PCR analysis. Results were verified by Western blot analysis.
Mice fed the Ath diet had significantly higher plasma TC and FC levels relative to the control group. The mice on the Ath diet also had an increase in hepatic levels of total lipid, TG, and TC compared with the control diet. The addition of resveratrol reduced the increase in the plasma levels of TC and FC caused by the Ath induced diet. Histological grading of the liver sections confirmed that resveratrol significantly ameliorated both hepatic steatosis and inflammation that were present in the mice fed the Ath diet.
These researchers also found that the Ath diet up-regulated the mRNA expression of genes involved in lipogenesis, including Fdft1(farnesyl-diphosphate farnesyltransferase 1), Fasn (fatty acid synthase), and Pparg (peroxisome proliferators activated receptor gamma), and the addition of resveratrol to the diet reduced their expression. In contrast, the expression of factors involved in fatty acid beta-oxidation (lipolysis), such as PON1 (paraoxonase 1) and Ppara (peroxisome proliferators activated receptor alpha), were up-regulated by resveratrol treatment. Finally, the researchers observed that hepatic expression of SIRT1 was increased by the resveratrol treatment. Based on these results, they concluded that “our experiments demonstrated for the first time that resveratrol exerts a protective effect on Ath diet-induced steatohepatitis through the modulation of lipid-metabolism related genes….Our findings suggest that resveratrol has beneficial effects on the prevention and treatment of NASH associated with obesity.”
Source:
Ahn J, Cho I, Kim S, et al. Dietary resveratrol alters lipid metabolism-related gene expression of mice on an atherogenic diet. Journal of Hepatology. 2008;49:1019-1028
Original Article:
http://www.organiccenter.org/science.hot.php?action=view&report_id=147
Author(s): Chris McCullum-Gomez PhD, RD, LD
