Effect Of EGCG On Improving Bpa Induced Disorders Of Liver Metabolism And Intestinal Microbial Community In Mice

Bisphenol A(BPA)as environmental endocrine disruptor is widely distributed in water,soil,and other environments.Study showed that prolonged exposure to BPA could cause adverse impact for bodily systems and organs,leading to reproductive and developmental toxicity,neurotoxicity,endocrine disrupting effect.The impact of BPA on lipid metabolism disorder has been a topic of much research interest.(-)-Epigallocatechin-3-gallate(EGCG)as a bioactive component in green tea possessed a positive impact on improving lipid metabolism disorder by inhibiting the differentiation and proliferation of adipocytes,reducing the body weight and fat content of obese animals,and inhibiting lipogenesis.To investigate the impact of EGCG on BPA-induced lipid metabolism disorder in mice,we established a mouse model of lipid metabolism disorder through BPA.Then,the mice were intervened with EGCG and measured the physiological and biochemical indicators related to lipid metabolism in mice to determine the effectiveness of EGCG in improving BPAinduced lipid metabolism disorder.Next,the effect of BPA on intestinal microorganism and metabolic phenotype of mice was explored under EGCG intervention by using microbiomics and metabolomics to reveal the molecular mechanism.The main research results are as follows:(1)Based on previous reports,a mouse model of lipid metabolism disorder under BPA exposure was constructed.The body weight,liver weight and liver/body weight ratio of mice exposed to BPA(0.5 μg/kg/d,the daily exposure dose for humans)were 37.2 g,2.15 g and4.28,respectively,which were significantly increased compared with the control group.In addition,the levels of triglyceride and cholesterol in mouse liver and serum increased,and lipid accumulation occurred in mice liver exposed to BPA.(2)Based on the above model,the physiological and biochemical indicators of mice under EGCG intervention were measured.After 12 weeks of exposure,the body weight and liver weight of low-dose EGCG treatment group were 33.8g and 1.79 g,respectively,and those of high-dose EGCG treatment group were 32.7g and 1.88 g,respectively.Compared with BPA treatment group,the body weight,liver weight and triglyceride and cholesterol levels of mice decreased significantly,and lipid metabolism improved.In addition,low-dose EGCG had a better improvement effect than high-dose EGCG.(3)The expression of genes related to lipid synthesis and metabolism in mice under EGCG intervention.The experimental results showed that the expression of Elovl6 gene related to fatty acid biosynthesis and Lss gene related to cholesterol biosynthesis in mice significantly increased after BPA exposure.EGCG intervention significantly reduced the expression of Elovl6 and Lss genes.In addition,EGCG promoted the expression of CYP4A14 gene related to fatty acid oxidation and CYP7a1 gene related to cholesterol metabolism in mice,achieving the regulation of BPA-induced lipid metabolism disorder.(4)The effect of EGCG on intestinal microorganism of mice.The experimental results showed that Firmicutes(97.25%)increased significantly and Acidobacteria(1.88%)at the phylum level decreased significantly in BPA treatment group compared with the control group.At the genus level,Lactobacillus(81.33%)and Bacillus(8.60%)were abundant in control group,while Lactobacillus abundance increased to 95.09% in BPA treatment group,and Bacillus abundance decreased significantly to 0.33%.After EGCG intervention,the composition of dominant phylum and genus in mice intestine was tended to be consistent with that in control group.(5)The effect of EGCG on serum metabolites of mice.Based on the metabolic phenotype between control group and BPA treatment group,121 different metabolites were screened and identified.Among 92 different metabolites including taurine,citrulline,cholestenone,glycerophosphocholine,4-(2-aminophenyl)-2,4-dioxobutanoic acid,glycocholic acid,and cholesterol glucuronide were significantly up-regulated;and other 29 different metabolites including malonic acid,N-acetyl-L-glutamate-5-semialdehyde,thyrotropin releasing hormone,and 1-piperideine-2-carboxylic acid were significantly down-regulated.After EGCG intervention,some different metabolites could be tended to be consistent with that in control group.EGCG might regulate primary bile acid biosynthesis and tryptophan metabolism to improve BPA-induced lipid metabolism disorder in mice.In summary,EGCG could improve BPA-induced lipid metabolism disorder in mice by affecting fatty acid,cholesterol biosynthesis and metabolism,and intestinal microbiota community structure and composition.The results provided data support and theoretical basis for the risk assessment of BPA and the efficient utilization of EGCG.