Berberine alleviates non-alcoholic hepatic steatosis partially by promoting SIRT1 deacetylation of CPT1A in mice  

作　　者：Peng Wang Ruikai Li Yuqi Li Siwei Tan Jie Jiang Huiling Liu Xiuqing Wei 

机构地区：[1]Department of Gastroenterology,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong,P.R.China

出　　处：《Gastroenterology Report》2023年第1期316-330,共15页胃肠病学报道（英文）

基　　金：supported by the Science and Technology Foundation of Guangzhou,China[No.201903010099].

摘　　要：Background:Berberine effectively alleviates non-alcoholic fatty liver disease(NAFLD).Nevertheless,the mechanism is incompletely comprehended.It has been reported that SIRT1 mediates lipid metabolism in liver and berberine promotes the expression of SIRT1 in hepatocytes.We hypothesized that SIRT1 mediated the effect of berberine on NAFLD.Methods:The effects of berberine on NAFLD were evaluated in C57BL/6J mice fed a high-fat diet(HFD)and in mouse primary hepatocytes and cell lines exposed to palmitate.The change of fatty acid oxidation(FAO)and the activity of CPT1A were observed in HepG2 cells.Quantitative real-time polymerase chain reaction and Western blot were employed to observe the expression of SIRT1 and lipid metabolism-related molecules.The interaction between SIRT1 and CPT1A was investigated by using co-immunoprecipitation assay in HEK293T cells.Results:Berberine treatment attenuated hepatic steatosis,reduced triglyceride(190.1611.2 lmol/g liver vs 113.667.6 lmol/g liver,P<0.001)and cholesterol(11.362.5 lmol/g liver vs 6.360.4 lmol/g liver,P<0.001)concentration in the liver,and improved lipid and glucose metabolism disorders compared with the HFD group.The expression of SIRT1 was reduced in the liver of NAFLD patients and mouse models.Berberine increased the expression of SIRT1 and promoted the protein level of CPT1A and its activity in HepG2 cells.SIRT1 overexpression mimicked the effect of berberine on reducing triglyceride levels in HepG2 cells,whereas SIRT1 knock-down attenuated the effect of berberine.Mechanistically,berberine increased the expression of SIRT1.SIRT1 deacetylated CPT1A at the Lys675 site,which suppressed its ubiquitin-dependent degradation,thereby promoting FAO and alleviating non-alcoholic liver steatosis.Conclusions:Berberine promoted SIRT1 deacetylation of CPT1A at the Lys675 site,which reduced the ubiquitin-dependent degradation of CPT1A and ameliorated non-alcoholic liver steatosis.

关 键 词：BERBERINE non-alcoholic fatty liver disease SIRT1 carnitine palmitoyltransferase 1A ACETYLATION 

分 类 号：R575[医药卫生—消化系统]