Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Phytother Res. 2019 Dec;33(12):3140-3152. doi: 10.1002/ptr.6486. Epub 2019 Aug 26.

Abstract

Multiphase pathological processes involve in Type 2 diabetes (T2DM)-induced nonalcoholic fatty liver disease (NAFLD). However, the therapies are quite limited. In the present study, the hepatoprotective effects and underlying mechanisms of quercetin in T2DM-induced NAFLD were investigated. T2DM-induced NAFLD and quercetin treatment models were established in vivo and in vitro. The results revealed that quercetin alleviated serum transaminase levels and markedly reduced T2DM-induced histological alterations of livers. Additionally, quercetin restored superoxide dismutase, catalase, and glutathione content in livers. Not only that, quercetin markedly attenuated T2DM-induced production of interleukin 1 beta, interleukin 6, and TNF-α. Accompanied by the restoration of the increased serum total bile acid (p = .0001) and the decreased liver total bile acid (p = .0005), quercetin could reduce lipid accumulation in the liver of db/db mice. Further mechanism studies showed that farnesoid X receptor 1/Takeda G-protein-coupled receptor 5 signaling pathways was involved in quercetin regulation of lipid metabolism in T2DM-induced NAFLD. In high D-glucose and free fatty acid cocultured HepG2 cells model, quercetin eliminated lipid droplets and restored the upregulated total cholesterol and triglyceride levels. Similar to the findings in mice, quercetin could also activate farnesoid X receptor 1/Takeda G-protein-coupled receptor 5 signaling pathway. These findings suggested that quercetin might be a potentially effective drug for the treatment of T2DM-induced NAFLD.

Keywords: FXR1/TGR5 signaling pathways; Type 2 diabetes; inflammation; lipid metabolism; nonalcoholic fatty liver; quercetin.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Humans
  • Inflammation / drug therapy*
  • Lipid Metabolism / drug effects*
  • Liver / drug effects*
  • Male
  • Mice
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Oxidative Stress / drug effects*
  • Quercetin / pharmacology
  • Quercetin / therapeutic use*
  • Signal Transduction

Substances

  • Antioxidants
  • Quercetin