The Mechanisms Of Phytosterol Ester On Non-alcoholic Fatty Liver Disease Metabolism

With the change of diet and lifestyle,the incidence of non-alcoholic fatty liver disease(NAFLD)has increased year by year.The early NAFLD is simple steatosis,but it can gradually progressed to non-alcoholic steatohepatitis,liver fibrosis,cirrhosis,and eventually develop into liver cancer without timely correction.Therefore,the prevention and early intervention of NAFLD is of great significance.Previous studies have indicated that phytosterol ester(PSE)has cholesterol-lowering,lipid-lowering,anti-oxidation,anti-inflammatory and other biological activities.Our previous studies have found that PSE can effectively reduce the hepatic steatosis in the NAFLD rats with an unknown mechanism.In this study,four-week-old SD rats were fed with high-fat diet(HF group)to establish the NAFLD model and PSE(0.05g/100 g · body weight)was given(HF+PSE group)using intragastric gavage.After 12 weeks,the fatty acid profiles of serum,hepatic and adipose tissue were detected using gas chromatography-mass spectrometry(GC-MS)to observe the effects of PSE on the fatty acid metabolism of NAFLD rats.Amino acid profiles of serum and hepatic tissue were detected using amino acid analyzer to analyze the effects of PSE on amino acid metabolism.Further,the expression of lipid metabolism-related genes in hepatic and adipose tissue of rats was detected using real-time PCR to preliminary research the molecular mechanisms of the effect of PSE on the metabolism in NAFLD rats.The results are as follows:(1)Effects of PSE on fatty acid profile in NAFLD ratsCompared with HF group,PSE intervention decreased the hepatic tissue and serum total saturated fatty acids(SFAs)significantly(P<0.05),while increased total monounsaturated fatty acids(MUFAs)and polyunsaturated fatty acids(PUFAs)significantly(P<0.05).Among them,the reduced SFAs included C16:0,C18:0,C20:0,C22:0,C23:0 & C24:0,elevated MUFAs included C16:1,C18:1&C20:1,and raised PUFAs included: C18:2,C20:2,C20:3,C22:4,C22:6 and C22:5.(2)Effects of PSE on the amino acid profile of NAFLD rats.Compared with HF group,PSE intervention significantly increased the level of isoleucine,leucine,cysteine,asparagine,glutamate,alanine,β-alanine,α-amino butyric acid and ornithine in serum.Besides,PSE intervention significantly increased the content of methionine,valine,glutamic acid,alanine,asparagine,glutamineand ornithine in hepatic tissue.At the same time,it also significantly reduced blood ammonia and serum histidine.(3)Effects of PSE on lipid metabolism-related genes in NAFLD rats.PSE intervention significantly up-regulated the expression of FADS1,FADS2(P<0.01),and CPT1(P<0.05)in hepatic tissue compared with HF group.In addition,PSE significantly down-regulated the expression of CHREBP in hepatic tissue and LPL(P<0.05)in adipose tissue.Conclusion: PSE can alleviate the metabolism disorder of fatty acid and amino acid in NAFLD rats induced by high-fat diet,thus improving NAFLD.The mechanism may be related to the upregulation of FADS1 and FADS2 expression in hepatic tissue,down regulation of CHREBP expression in hepatic tissue and LPL expression in adipose tissue.