Hepatosteatosis is characterized by abnormal accumulation of triglycerides(TG),leading to prolonged and chronic inflammatory infiltration.To date,there is still a lack of effective and economical therapies for hepatos...Hepatosteatosis is characterized by abnormal accumulation of triglycerides(TG),leading to prolonged and chronic inflammatory infiltration.To date,there is still a lack of effective and economical therapies for hepatosteatosis.Oridonin(ORI)is a major bioactive component extracted from the traditional Chinese medicinal herb Rabdosia rubescens.In this paper,we showed that ORI exerted significant protective effects against hepatic steatosis,inflammation and fibrosis,which was dependent on LXRa signaling.It is reported that LXRa regulated lipid homeostasis between triglyceride(TG)and phosphatidylethanolamine(PE)by promoting ATGL and EPT1 expression.Therefore,we implemented the lipidomic strategy and luciferase reporter assay to verify that ORI contributed to the homeostasis of lipids via the regulation of the ATGL gene associated with TG hydrolysis and the EPT1 gene related to PE synthesis in a LXRadependent manner,and the results showed the TG reduction and PE elevation.In detail,hepatic TG overload and lipotoxicity were reversed after ORI treatment by modulating the ATGL and EPT1 genes,respectively.Taken together,the data provide mechanistic insights to explain the bioactivity of ORI in attenuating TG accumulation and cytotoxicity and introduce exciting opportunities for developing novel natural activators of the LXRa-ATGL/EPT1 axis for pharmacologically treating hepatosteatosis and metabolic disorders.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.:81973388)Marine Economy Development Project of Guangdong Province(Project No.:GDNRC[2021]52)the Key Research and Development Program of Guangdong Province(Program No.:2020B1111030005).
文摘Hepatosteatosis is characterized by abnormal accumulation of triglycerides(TG),leading to prolonged and chronic inflammatory infiltration.To date,there is still a lack of effective and economical therapies for hepatosteatosis.Oridonin(ORI)is a major bioactive component extracted from the traditional Chinese medicinal herb Rabdosia rubescens.In this paper,we showed that ORI exerted significant protective effects against hepatic steatosis,inflammation and fibrosis,which was dependent on LXRa signaling.It is reported that LXRa regulated lipid homeostasis between triglyceride(TG)and phosphatidylethanolamine(PE)by promoting ATGL and EPT1 expression.Therefore,we implemented the lipidomic strategy and luciferase reporter assay to verify that ORI contributed to the homeostasis of lipids via the regulation of the ATGL gene associated with TG hydrolysis and the EPT1 gene related to PE synthesis in a LXRadependent manner,and the results showed the TG reduction and PE elevation.In detail,hepatic TG overload and lipotoxicity were reversed after ORI treatment by modulating the ATGL and EPT1 genes,respectively.Taken together,the data provide mechanistic insights to explain the bioactivity of ORI in attenuating TG accumulation and cytotoxicity and introduce exciting opportunities for developing novel natural activators of the LXRa-ATGL/EPT1 axis for pharmacologically treating hepatosteatosis and metabolic disorders.
