Resolvin D1 ameliorates hepatic steatosis by remodeling the gut microbiota and restoring the intestinal barrier integrity in DSS-induced chronic colitis.

Background And Purpose: The maintenance of intestinalmucosalbarrier function plays an important role in hepatic steatosis. Increasing evidence has shown that resolvin D1 (RVD1) exerts a potential effect on hepatic steatosis. The aims of this study were to explore the mechanisms of RVD1 on hepatic steatosis based on the gut-liver axis and intestinal barrier function.

Experimental Approach: We established a DSS-induced chronic colitis model to evaluate hepatic steatosis. RVD1 was administered i.p. during the last 4 weeks. The colon and liver samples were stained with hematoxylin and eosin for histopathological analysis. The expression levels of intestinal tight junction genes and inflammatory genes were determined by quantitative PCR. The serum levels of glucose, cholesterol, triglycerides and LPS were measured, and the gut microbiota was analyzed by 16S rRNA gene sequencing.

Key Results: RVD1 prevented weight loss, histopathological changes, and elevated levels of inflammatory cytokines. Moreover, RVD1 administration attenuated DSS-induced hepatic steatosis and inflammatory responses in mice. In addition, RVD1 improved intestinal barrier function by increasing levels of tight junction molecules and decreasing the plasma LPS levels. The RVD1-treated mice also showed a different gut microbiota composition compared with found in the mice belonging to the DSS group but similar to that in normal chow diet-fed mice.

Conclusions And Implications: RVD1 treatment ameliorates DSS-induced hepatic steatosis by ameliorating gut inflammation, improving intestinal barrier function and modulating intestinal dysbiosis.