Ameliorative Effect of Myricetin on Nonalcoholic Fatty Liver Disease in ob/ob Mice

Abstract

Obesity, insulin resistance, and oxidative stress are important risk factors for nonalcoholic fatty liver disease (NAFLD). This study aimed at determining the beneficial effects of myricetin against NAFLD in ob/ob mice. C57BL/6-Lep^ob/ob mice (n = 21) were fed an AIN-93G diet (ob/ob control group) or diet containing 0.04% (low myricetin; LMTN group) or 0.08% (high myricetin; HMTN group) myricetin, and lean heterozygous littermates (lean control group, n = 7) were fed AIN-93G diet for 10 weeks. HMTN consumption significantly lowered serum glucose levels and homeostasis model assessment for insulin resistance values in ob/ob mice. In addition to reducing serum triglyceride (TG) and cholesterol levels, HMTN significantly decreased total hepatic lipid and TG levels partly through downregulation of carbohydrate response element-binding protein and sterol regulatory element-binding protein 1c expression. The reduction in the levels of hepatic thiobarbituric acid reactive substances by HMTN likely resulted from the elevation of nuclear factor erythroid-2-related factor 2 expression. Tumor necrosis factor-α and monocyte chemoattractant protein 1 expressions were reduced by LMTN and HMTN, and HMTN also decreased interleukin-6 expression. These results suggest that myricetin has beneficial effects against NAFLD by regulating the expression of transcription factors of hepatic lipid metabolism, the antioxidant system, and pro-inflammatory cytokines.

Keywords: insulin resistance; myricetin; nonalcoholic fatty liver disease (NAFLD); oxidative stress; pro-inflammatory cytokine.