Chitobiose exhibited a lipid-lowering effect in ob/ob^−/− mice via butyric acid enrolled liver–gut crosstalk

Abstract

Chitobiose (COS₂) efficiently lowers lipids in vivo and facilitates butyric acid enrichment during human fecal fermentation. However, whether COS₂ can interact with butyric acid to generate a hypolipidemic effect remains unclear. This study examined the hypolipidemic mechanism of COS₂ involving butyric acid, which could alleviate non-alcoholic fatty liver disease (NAFLD). The results revealed that COS₂ administration modulated the β-oxidation pathway in the liver and restructured the short chain fatty acids in the fecal of ob/ob^−/− mice. Moreover, the hypolipidemic effect of COS₂ and its specific accumulated metabolite butyric acid was verified in sodium oleate-induced HepG2 cells. Butyric acid was more effective to reverse lipid accumulation and up-regulate β-oxidation pathway at lower concentrations. Furthermore, structural analysis suggested that butyric acid formed hydrogen bonds with key residues in hydrophilic ligand binding domains (LBDs) of PPARα and activated the transcriptional activity of the receptor. Therefore, the potential mechanism behind the lipid-lowering effect of COS₂ in vivo involved restoring hepatic lipid disorders via butyric acid accumulation and liver–gut axis signaling.

Keywords

Chitobiose / Butyric acid / Non-alcoholic fatty liver disease / Lipid β-oxidation / Liver–gut axis signaling

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Funding

Shanghai Natural Science Foundation General program(23ZR1417300)

Shanghai post-doctoral Excellence Program(2022153)

National key R&D Program of China(2019YFD090180302)

111 Project(B18022)