Molecular nutrition & food research | 2019
Green Tea Extract Treatment in Obese Mice with Nonalcoholic Steatohepatitis Restores the Hepatic Metabolome in Association with Limiting Endotoxemia-TLR4-NFκB-Mediated Inflammation.
Abstract
SCOPE\nCatechin-rich green tea extract (GTE) alleviates nonalcoholic steatohepatitis (NASH) by lowering endotoxin-TLR4-NFκB inflammation. We aimed to define altered MS-metabolomic responses in a high-fat (HF)-induced NASH model that are restored by GTE utilizing livers from an earlier study in which GTE decreased endotoxin-TLR4-NFκB liver injury.\n\n\nMETHODS AND RESULTS\nMice were fed a low-fat (LF) or HF diet for 12-wk and then randomized to LF or HF diets containing 0% or 2% GTE for an additional 8-wk. Global MS-based metabolomics and targeted metabolite profiling of catechins/catechin metabolites were evaluated by UHPLC-QTOF. GTE in HF mice restored hepatic metabolites implicated in dysregulated lipid metabolism, insulin resistance, and inflammation. These included 122 metabolites: amino acids, lipids, nucleotides, vitamins, bile acids, flavonoids, xenobiotics, and carbohydrates. Hepatic amino acids, B-vitamins, and bile acids were inversely correlated (P<0.05) with biomarkers of insulin resistance, liver injury, steatosis, and inflammation. Further, phosphatidylcholine metabolites were positively correlated with biomarkers of liver injury and NFκB inflammation. Thirteen catechin metabolites were identified in livers of GTE-treated mice, mostly as phase II conjugates of parental catechins or microbial-derived valerolactones.\n\n\nCONCLUSION\nThe defined anti-inflammatory/metabolic interactions advance an understanding of the mechanism by which GTE catechins protect against NFκB-mediated liver injury in NASH. This article is protected by copyright. All rights reserved.