RESUMO
Background:Non-alcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases worldwide and specific targeted therapy is still lacking up to now. Aims:To investigate the protective effect of berberine on high fat diet(HFD)-induced hepatic lipotoxicity in mice and its potential mechanisms. Methods:Thirty male C57BL/6J mice were randomly assigned to three groups,then fed either with standard diet or HFD or HFD plus berberine(200 mg/kg per day intragastrically)for 12 weeks. Serum biochemical indices including ALT,AST,TC,TG and glucose were measured at the end of the 12th week. HE staining was used to observe liver inflammation,and fatty infiltration was detected with oil red staining. Ileocecal feces was collected and the composition of gut microbiota was analyzed by 16S rRNA sequencing. Serum level of LPS and hepatic levels of TNF-α and IL-6 were detected by ELISA. In vitro,the primary hepatic macrophages of C57BL/6J mice were challenged with palmitic acid,LPS and/or berberine,respectively;the ultrastructure of macrophages was observed using electron microscope,and the proinflammatory cytokines were detected by real-time PCR. Results:In vivo,the treatment of berberine improved the liver dysfunction,hyperlipidemia and hyperglycemia in mice fed with HFD. Also,berberine significantly inhibited the HFD-induced hepatic lipid accumulation,and alleviated hepatocytes ballooning and lobular inflammatory cell infiltration;the levels of serum LPS and hepatic IL-6 were markedly decreased. 16S rRNA sequencing showed that berberine supplementation restored the abundance of Bacteroidaceae and Desulfovibrionaceae in ileocecus,which were disturbed by HFD. In vitro,berberine not only significantly reduced the palmitic acid-induced lipid accumulation in primary hepatic macrophages,but also decreased the expressions of TNF-α and IL-6 in macrophages stimulated with LPS. Conclusions:Berberine can ameliorate effectively the hepatic lipid accumulation and inflammation in mice with experimental NAFLD. The mechanism of its antiinflammatory effect might be related with regulating the gut microbiota,reducing the LPS production,and subsequently inhibiting the release of inflammatory cytokines by hepatic macrophages.