Epigallocatechin Gallate Alleviates Metabolic Abnormality And Fatty Liver By Decreasing Bile Acid And Lipid Absorption In Mice

In recent years,with the improvements of living standard and the changes of dietary pattern,the morbidity of metabolic diseases are increasing,and the treatment or prevention of these illnesses have become a research focus in food nutrition field.As a heath beverage,the benefits of tea were frequently reported,and the mechanisms of its metaolic syndrome-alleviating effects were investigated by many research groups.(-)epigallocatechin–3–gallate(EGCG)is a bioactive substance with the highest content and the most important function in tea,which has pronounced effacies in amiliorating metabolic abnomality and fatty liver.However,the underlying mechanisms of these functions by EGCG are largely unkown.Based on our previous study,the effects of EGCG on lipid components of serum and liver in mice fed on high fat western diet were examined using lipidomics method,and the roles of bile acid homostasis in alleviating metabolic abnomality by EGCG were also illustrated.A total of 50 male C57BL/6J mice were selected and randomly divided into three groups: Low fat diet group(low fat diet,n= 10,LF),High fat western diet gorup(high fat western diet,n=20,HFW)and EGCG treatment goup(high fat western diet +3.2g/kgEGCG,n=20).The test period was 17 weeks.All the mice received diets and tap water ad libitum throughout the experiment.The body weights,food and drink consumptions of mice were monitored every week,the fasting blood glucose levels and tail vein blood samples were determined and collected,respectively,every four weeks.The main results were as follows:1.Compared with the HFW group mice,EGCG treatment significantly reduced the animal's body weight and inhibited the accumulation of epididymal adipose and mesenteric adipose.At week 12,compared with the HFW group,the blood glucose level of the EGCG group was reduced by 22.0%(P<0.05).The plasma insulin and insulin resistance index(HOMA-IR)decreased by 39.1% and 53.1%,respectively(P<0.05).At 16 weeks,EGCG treatment significantly reduced serum concentrations of total cholesterol(20.8%,P<0.05)and low-density lipoprotein cholesterol(27.9%,P<0.05),and significantly suppressed high-fat diet induced alanine aminotransferase.(ALT)increased.At the same time,EGCG treatment reduced the accumulation of hepatic total fat(36.0%,P<0.05)and cholesterol(32.4%,P<0.05)in obese mice and inhibited the occurrence of fatty liver.2.The analyzed of liver and serum samples by lipidomics showed that,a total of 33 free fatty acid species and 179 lipid species were identified in the liver.Compared with the high fat diet group,EGCG treatment group significantly changed the 72 lipids,DG and TG were the two most abundant classes altered by dietary treatments.EGCG treatment prevented the HFW-induced 24 DG species levels.Among TG species,EGCG significantly reduced the species with more unsaturated fatty acids and increased levels of the species less unsaturated fatty acids.A total of 37 FFAs and 175 other lipid species were identified in serum.In comparison to the HFW group,EGCG treatments significantly changed the levels of 64 lipid species,FFA,PC and DG were the three most variable substances.Compared with the high-fat group,EGCG significantly reduced total FFA levels in the serum,PC species levels and 50% of the DG species were increased by EGCG treatment.3.Compared with the high-fat group animals,the total bile acid pool and intestinal bile acid contents in the EGCG group were decreased by 31.3% and 29.1%(P<0.05),respectively.The feces bile acid content significantly increased by 150.0%(P<0.05).At the same time,EGCG increased excretion of total fecal lipids(25.8%,P<0.05)and total cholesterol(38.4%,P<0.05).Real-time quantitative PCR data showed that,mRNA levels of cholesterol 7? hydroxylase(Cyp7a1),sterol 12? hydroxylase(Cyp27a1)and farnesoid X receptor(FXR)in the liver of EGCG mice increased 530.0%,200.0%,and 90.0%(P<0.05),compared with those in the HFW group.Whereas ileal mRAN on the transcriptional levels of genes fibroblast growth factor 15(FGF15),ATP-binding transporter G superfamily member 5(ABCG5),sodium-dependent bile salt transporter(ASBT)was no significant difference in all groups.At the same time,EGCG treatment significantly up-regulated liver cholesterol synthesis and uptake-associated genes HMG-CoA reductase(HMGR,230%,P<0.05),low-density lipoprotein receptor(LDLR,100.0%,P<0.05)and scavenger receptor B1(SR-B1,60.0%,P<0.05)mRNA level.Down-regulated the Cluster of differentiation 36(CD36,62.4%,P<0.05)mRNA expression levels of key genes related to the fatty acid metabolism.In conclusion,dietary EGCG significantly improves the abnormal metabolism and fatty liver disease induce by the high-fat Western diet(HFW),changed the composition of lipid in liver and serum,effectively decreases bile acid reabsorption,further decrease the absorption of lipids.This study provides a new way for the mechanism of EGCG to alleviate the metabolic syndrome and the fatty liver disease.