Since metabolic process differs between humans and mice, studies were performed in hamsters, which are generally considered to be a more appropriate animal model for studies of obesityrelated metabolic disorders. The ...Since metabolic process differs between humans and mice, studies were performed in hamsters, which are generally considered to be a more appropriate animal model for studies of obesityrelated metabolic disorders. The modulation of gut microbiota, bile acids and the farnesoid X receptor(FXR) axis is correlated with obesity-induced insulin resistance and hepatic steatosis in mice. However,the interactions among the gut microbiota, bile acids and FXR in metabolic disorders remained largely unexplored in hamsters. In the current study, hamsters fed a 60% high-fat diet(HFD) were administeredvehicle or an antibiotic cocktail by gavage twice a week for four weeks. Antibiotic treatment alleviated HFD-induced glucose intolerance, hepatic steatosis and inflammation accompanied with decreased hepatic lipogenesis and elevated thermogenesis in subcutaneous white adipose tissue(sWAT). In the livers of antibiotic-treated hamsters, cytochrome P450 family 7 subfamily B member 1(CYP7 B1) in the alternative bile acid synthesis pathway was upregulated, contributing to a more hydrophilic bile acid profile with increased tauro-β-muricholic acid(TβMCA). The intestinal FXR signaling was suppressed but remained unchanged in the liver. This study is of potential translational significance in determining the role of gut microbiota-mediated bile acid metabolism in modulating diet-induced glucose intolerance and hepatic steatosis in the hamster.展开更多
基金supported by the National Key Research and Development Program of China(grant No.SQ2018YFC100236)the National Natural Science Foundation of China(grant Nos.91857115,81522007,81470554,31401011,and 81700010)+1 种基金the Fundamental Research Funds for the Central Universities:Clinical Medicine Plus X-Young Scholars Project of Peking University(grant No.PKU2018LCXQ013,China)Beijing Nova Program(grant No.Z161100004916056,China)
文摘Since metabolic process differs between humans and mice, studies were performed in hamsters, which are generally considered to be a more appropriate animal model for studies of obesityrelated metabolic disorders. The modulation of gut microbiota, bile acids and the farnesoid X receptor(FXR) axis is correlated with obesity-induced insulin resistance and hepatic steatosis in mice. However,the interactions among the gut microbiota, bile acids and FXR in metabolic disorders remained largely unexplored in hamsters. In the current study, hamsters fed a 60% high-fat diet(HFD) were administeredvehicle or an antibiotic cocktail by gavage twice a week for four weeks. Antibiotic treatment alleviated HFD-induced glucose intolerance, hepatic steatosis and inflammation accompanied with decreased hepatic lipogenesis and elevated thermogenesis in subcutaneous white adipose tissue(sWAT). In the livers of antibiotic-treated hamsters, cytochrome P450 family 7 subfamily B member 1(CYP7 B1) in the alternative bile acid synthesis pathway was upregulated, contributing to a more hydrophilic bile acid profile with increased tauro-β-muricholic acid(TβMCA). The intestinal FXR signaling was suppressed but remained unchanged in the liver. This study is of potential translational significance in determining the role of gut microbiota-mediated bile acid metabolism in modulating diet-induced glucose intolerance and hepatic steatosis in the hamster.
