Angelica sinensis polysaccharide ameliorates nonalcoholic fatty liver disease via restoring estrogen‐related receptor α expression in liver

Abstract Angelica sinensis polysaccharide (ASP) showed increasingly recognized hepatoprotective effects and lipid regulation. Because polysaccharides are typically degraded into fragments or short‐chain fatty acids in the gut, rather than being absorbed in their intact form, it is worth pondering why ASP can regulate hepatic lipid metabolism and protect the liver from damage caused by lipid accumulation. In vivo and in vitro nonalcoholic fatty liver disease (NAFLD) models with lipid accumulation were established to investigate the effect and potential mechanisms of ASP on hepatic fat accumulation. Our results showed that ASP remodeled the composition and abundance of the gut microbiota in high‐fat diet‐fed mice and increased their levels of propionate (0.92 ± 0.30 × 10 7 vs. 2.13 ± 0.52 × 10 7 ) and butyrate (1.83 ± 1.31 × 10 7 vs. 6.39 ± 1.44 × 10 7 ). Sodium propionate significantly increased the expression of estrogen‐related receptor α (ERRα) in liver cells (400 mM sodium propionate for 2.19‐fold increase) and alleviated the progress of NAFLD in methionine–choline‐deficient diet model. Taken together, our study demonstrated that ASP can regulate hepatic lipid metabolism via propionate/ERRα pathway and ultimately relieving NAFLD. Our findings demonstrate that ASP can be used as a health care product or food supplement to prevent NAFLD.