期刊
PHYTOTHERAPY RESEARCH
卷 33, 期 12, 页码 3140-3152出版社
WILEY
DOI: 10.1002/ptr.6486
关键词
FXR1; TGR5 signaling pathways; inflammation; lipid metabolism; nonalcoholic fatty liver; quercetin; Type 2 diabetes
资金
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- National Natural Science Foundation of China [81400741, 81473257]
- 333 Foundation of Jiangsu Province [BRA2015329]
- Key Natural Science Foundation of Jiangsu Higher Education Institutions of China [19KJA460008, 15KJA310005]
- Natural Science Foundation of Jiangsu Province [BK20151155]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Jiangsu Overseas Research & Training Program for University Young & Middle-aged Teachers and Presidents
- Qing Lan project
- Xuzhou Medical University [53681720]
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-alpha. 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.
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