Ganoderma lucidum polysaccharide peptide alleviates hepatoteatosis via modulating bile acid metabolism dependent on FXR-SHP/FGF  

作　　者：ZHONG Dan-dan YANG Bao-xue 

机构地区：[1]State Key Laboratory of Natural and Biomimetic Drugs,Department of Pharmacology,School of Basic Medical Sciences,Peking University

出　　处：《中国药理学与毒理学杂志》2019年第9期703-704,共2页Chinese Journal of Pharmacology and Toxicology

基　　金：National Natural Science Foundation of China(81330074;81620108029;81261160507);Beijing Natural Science Foundation(7172113)

摘　　要：OBJECTIVE Ganoderma lucidum polysaccharide peptide(GLPP)is a group of extract from Ganoderma lucidum with a molecular mass of approximately 5×10^5,which ratio of polysaccharide to peptide is approximately 95%/5%.The purpose of this study was to determine whether GLPP has therapeutic effect on Non-alcoholic fatty liver disease(NAFLD).METHODS Ob/ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD.Key metabolic pathways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blotting.Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD.RESULTS GLPP administrated for a month alleviated hepatosteatosis,dyslipidemia,liver dysfunction and liver insulin resistance.Pathways of glycerophos⁃pholipid metabolism,fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD.Detection of key enzymes revealed that GLPP reversed low expression of CYP7A1,CYP8B1,FXR,SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice.Besides,GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1c,FAS and ACC via a FXR-SHP dependent mechanism.Additionally,GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepatocytes induced by oleic acid and palmitic acid.CONCLUSION GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway,which finally inhibits fatty acid synthesis,indicating that GLPP might be developed as a ther⁃apeutic drug for NAFLD.OBJECTIVE Ganoderma lucidum polysaccharide peptide(GLPP) is a group of extract from Ganoderma lucidum with a molecular mass of approximately 5×105, which ratio of polysaccharide to peptide is approximately 95%/5%. The purpose of this study was to determine whether GLPP has therapeutic effect on Non-alcoholic fatty liver disease(NAFLD). METHODS Ob/ob mouse model and Apo C3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD. Key metabolic pathways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blotting. Hepatosteatosis models of HepG 2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD. RESULTS GLPP administrated for a month alleviated hepatosteatosis, dyslipidemia, liver dysfunction and liver insulin resistance. Pathways of glycerophospholipid metabolism, fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD. Detection of key enzymes revealed that GLPP reversed low expression of CYP7 A1, CYP8 B1, FXR,SHP and high expression of FGFR4 in ob/ob mice and Apo C3 mice. Besides, GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1 c, FAS and ACC via a FXR-SHP dependent mechanism. Additionally, GLPP reduced the accumulation of lipid droplets and the content of TG in HepG 2 cells and primary hepatocytes induced by oleic acid and palmitic acid. CONCLUSION GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway, which finally inhibits fatty acid synthesis, indicating that GLPP might be developed as a therapeutic drug for NAFLD.

关 键 词：Ganoderma lucidum polysaccharide peptide NAFLD insulin resistance HEPATOSTEATOSIS metabolo⁃mics bile acid synthesis nuclear receptors fatty acid synthesis 

分 类 号：R57[医药卫生—消化系统]