Nonalcoholic fatty liver disease (NAFLD) is a global epidemic, and there is no\nstandard and effcient therapy for it. Chitosan oligosaccharide (COS) is widely known to have\nvarious biological effects, and in this study we aimed to evaluate the liver-protective effect in\ndiet-induced obese mice for an enzymatically digested product of COS called COS23 which is mainly\ncomposed of dimers and trimers. An integrated analysis of the lipidome and gut microbiome\nwere performed to assess the effects of COS23 on lipids in plasma and the liver as well as on\nintestinal microbiota. Our results revealed that COS23 obviously attenuated hepatic steatosis\nand ameliorated liver injury in diet-induced obese mice. The hepatic toxic lipids-especially\ntriglycerides (TGs) and free fatty acids (FFAs)-were decreased dramatically after COS23 treatment.\nCOS23 regulated lipid-related pathways, especially inhibiting the expressions of FFA-synthesis-related\ngenes and inflammation-related genes. Furthermore, COS23 could alter lipid profiles in plasma.\nMore importantly, COS23 also decreased the abundance of Mucispirillum and increased the abundance\nof Coprococcus in gut microbiota and protected the intestinal barrier by up-regulating the expression\nof tight-junction-related genes. In conclusion, COS23, an enzymatically digested product of COS,\nmight serve as a promising candidate in the clinical treatment of NAFLD.
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