Jinbao Huang1,2, Simin Feng1,3, Anna Liu1, Zhuqing Dai1,4, Hong Wang1, Kenneth Reuhl5, Wenyun Lu6, Chung S Yang1,2. 1. Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ, USA. 2. International Joint Research Laboratory of Tea Chemistry and Health Effects, State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei, P. R. China. 3. Visiting student from Department of Food Science and Nutrition, Zhejiang University, Hangzhou, P. R. China. 4. Visiting student from College of Food Science and Technology, Nanjing Agricultural University, Nanjing, P. R. China. 5. Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ, USA. 6. Department of Chemistry & Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Abstract
SCOPE: The tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been shown to ameliorate metabolic abnormalities and fatty liver. The present study investigates the mechanisms of actions of EGCG on bile acid homeostasis and lipid metabolism. METHODS: Male C57BL/6J mice are fed a low-fat diet, a high-fat western-style diet, or a high-fat western-style diet containing 0.32% EGCG. The effects of the treatments on biochemical parameters, gene expression, and lipidomics are analyzed. RESULTS: EGCG treatment significantly reduces body weight gain, mesenteric fat mass, fasting blood glucose, insulin resistance, serum cholesterol, and severity of fatty liver after treatment for 17 weeks, but most of these effects were less apparent at week 33. At week 17, EGCG treatment significantly elevates the mRNA levels of cholesterol 7α-hydroxylase, HMG-CoA reductase, low-density lipoprotein receptor, and scavenger receptor B1, and partially normalizes the high-fat diet induced lipidomic profile. The intestinal bile acid content is significantly decreased by EGCG, while fecal excretion of bile acids, cholesterol, and total lipids are increased. CONCLUSION: EGCG decreases bile acid reabsorption, results in lower intestinal bile acid levels, which further decreases the absorption of lipids. These actions contribute to the alleviation of metabolic abnormalities and fatty liver disease caused by the high-fat diet.
SCOPE: The teapolyphenol (-)-epigallocatechin-3-gallate (EGCG) has been shown to ameliorate metabolic abnormalities and fatty liver. The present study investigates the mechanisms of actions of EGCG on bile acid homeostasis and lipid metabolism. METHODS: Male C57BL/6J mice are fed a low-fat diet, a high-fat western-style diet, or a high-fat western-style diet containing 0.32% EGCG. The effects of the treatments on biochemical parameters, gene expression, and lipidomics are analyzed. RESULTS:EGCG treatment significantly reduces body weight gain, mesenteric fat mass, fasting blood glucose, insulin resistance, serum cholesterol, and severity of fatty liver after treatment for 17 weeks, but most of these effects were less apparent at week 33. At week 17, EGCG treatment significantly elevates the mRNA levels of cholesterol 7α-hydroxylase, HMG-CoA reductase, low-density lipoprotein receptor, and scavenger receptor B1, and partially normalizes the high-fat diet induced lipidomic profile. The intestinal bile acid content is significantly decreased by EGCG, while fecal excretion of bile acids, cholesterol, and total lipids are increased. CONCLUSION:EGCG decreases bile acid reabsorption, results in lower intestinal bile acid levels, which further decreases the absorption of lipids. These actions contribute to the alleviation of metabolic abnormalities and fatty liver disease caused by the high-fat diet.
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