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.

Amelioration of the Lipogenesis, Oxidative Stress and Apoptosis of Hepatocytes by a Novel Proteoglycan from <i>Ganoderma lucidum</i>

“…18) Zhong et al reported that the Ganoderma lucidum polysaccharide peptide (GLPP) can alleviate hepatoteatosis. 31) Our previous study demonstrated that FYGL had an antihyperlipidemic effect in addition to antidiabetic in vivo. 24) Our studies on the mechanism found that FYGL improved the p-AMPK level along with the p-ACC and CPT-1 expressions increased, inhibited the expressions of fat-synthesis-related proteins FASN and SREBP1, leading to the steatosis inhibition, which implied that FYGL inhibit the lipid synthesis through AMPK pathway.…”

Ganoderic acid hinders renal fibrosis via suppressing the TGF-β/Smad and MAPK signaling pathways

“…Numerous bioactive constituents of G. lucidum , including terpenes, proteins, polysaccharides, amino acids, flavonoids, alkaloids, steroids, mannitol, and other compounds, have been revealed [ 12 ]. Pharmacological studies have determined that G. lucidum polysaccharides and triterpenes have multiple pharmacological activities [ 13 – 16 ].…”

Optimization of Porphyran Extraction from Pyropia yezoensis by Response Surface Methodology and Its Lipid-Lowering Effects

“…According to a previous study, the PA-induced HepG2 cell hepatosteatosis model is commonly used that identify bioactive compounds to inhibit lipid accumulation. For example, Zhong et al demonstrated that the Ganoderma lucidum polysaccharide peptide (GLPP) reduced the accumulation of lipid droplets and the content of TG in the hepatosteatosis model of HepG2 cells [46]. Huang et al reported the preventive and therapeutic effects of resveratrol on PA-induced hepatocyte steatosis in HepG2 cells [47].…”