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Published on: September 12, 2019
Sinensetin ameliorates established high-fat diet-induced liver injury and intestinal barrier dysfunction through the
Zhuoqun Meng1, Qin Zhang1, Zhichang Zhao1
1School of Food and Bioengineering, Xihua University, Chengdu, Sichuan, China.
Introduction:
Long-term consumption of a high-fat diet (HFD) causes liver injury characterized by steatosis, inflammation, and fibrosis. Mitophagy, as a selective autophagy, is reported to be involved in the regulation of liver injury. Sinensetin, a polymethoxylated flavonoid abundant in citrus fruit peels, exhibits various biological activities, including anti-inflammatory and hepatoprotective properties. However, whether sinensetin can target mitophagy and protect against HFD-induced liver damage via the gut-liver axis remains inadequately explored.
Methods:
In order to further investigate the relationships involved, we conducted histopathology analysis, biochemical analysis, 16S rRNA sequencing, and short-chain fatty acid (SCFA) levels.
Results:
Sinensetin administration ameliorated hepatic steatosis, inflammation, and restored intestinal integrity in HFD-fed mice. Mechanistically, sinensetin remodeled the gut microbiota, elevating SCFA levels, which activated mitophagy and cleared damaged mitochondria in liver and intestinal tissues, thereby suppressing the toll-like receptor 4 (TLR4)/mitogen-activated protein kinase (MAPK) signaling.
Conclusion:
Sinensetin may contribute to protecting against HFD-induced liver injury and intestinal barrier dysfunction by orchestrating the integrated "microbiota-SCFA-mitophagy" defensive network, providing a novel paradigm beyond the classical TLR4/MAPK axis.