Ganoderma Lucidum Polysaccharide Peptide Alleviates Hepatoteatosis via Modulating Bile Acid Metabolism Dependent on FXR-SHP/FGF.

Abstract

BACKGROUND/AIMS:

Non-alcoholic fatty liver disease (NAFLD) encompasses a series of pathologic changes ranging from steatosis to steatohepatitis, which may progress to cirrhosis and hepatocellular carcinoma. The purpose of this study was to determine whether ganoderma lucidum polysaccharide peptide (GLPP) has therapeutic effect on 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 blot. 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 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 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 therapeutic drug for NAFLD.

• Authors: Dandan Zhong, Zhengwei Xie, Boyue Huang, Shuai Zhu, Guoqian Wang, Hong Zhou, Shuqian Lin, Zhibin Lin, Baoxue Yang
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 49 Issue 3 Pg. 1163-1179 ( 2018) ISSN: 1421-9778 [Electronic] Germany
• PMID: 30196282 (Publication Type: Journal Article)
• Copyright: © 2018 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Bile Acids and Salts
• Proteoglycans
• Receptors, Cytoplasmic and Nuclear
• nuclear receptor subfamily 0, group B, member 2
• polysaccharide peptide
• Fragile X Mental Retardation Protein
• Oleic Acid
• Fibroblast Growth Factors
• Cholesterol 7-alpha-Hydroxylase
• Cyp7a1 protein, mouse

Topics

• Animals
• Bile Acids and Salts (metabolism)
• Cholesterol 7-alpha-Hydroxylase (metabolism)
• Fibroblast Growth Factors (metabolism)
• Fragile X Mental Retardation Protein (metabolism)
• Hep G2 Cells
• Hepatocytes (cytology, drug effects, metabolism)
• Humans
• Lipid Droplets (metabolism)
• Lipid Metabolism (drug effects)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Non-alcoholic Fatty Liver Disease (drug therapy, pathology)
• Oleic Acid (pharmacology)
• Proteoglycans (pharmacology, therapeutic use)
• Receptors, Cytoplasmic and Nuclear (metabolism)
• Reishi (metabolism)
• Signal Transduction (drug effects)