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Green Tea Extract Treatment in Obese Mice with Nonalcoholic Steatohepatitis Restores the Hepatic Metabolome in Association with Limiting Endotoxemia‐TLR4‐NFκB‐Mediated Inflammation
Author(s) -
Sasaki Geoffrey Y.,
Li Jinhui,
Cichon Morgan J.,
Riedl Ken M.,
Kopec Rachel E.,
Bruno Richard S.
Publication year - 2019
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201900811
Subject(s) - green tea extract , inflammation , insulin resistance , pharmacology , liver injury , steatohepatitis , endocrinology , medicine , biochemistry , cd36 , catechin , chemistry , biology , fatty liver , receptor , insulin , antioxidant , polyphenol , food science , disease , green tea
Scope Catechin‐rich green tea extract (GTE) alleviates nonalcoholic steatohepatitis (NASH) by lowering endotoxin‐TLR4 (Toll‐like receptor‐4)‐NFκB (nuclear factor kappa‐B) inflammation. This study aimed to define altered MS‐metabolomic responses during high‐fat (HF)‐induced NASH that are restored by GTE utilizing livers from an earlier study in which GTE decreased endotoxin‐TLR4‐NFκB liver injury. Methods and results Mice are fed a low‐fat (LF) or HF diet for 12 weeks and then randomized to LF or HF diets containing 0% or 2% GTE for an additional 8 weeks. Global MS‐based metabolomics and targeted metabolite profiling of catechins/catechin metabolites are evaluated. GTE in HF mice restores hepatic metabolites implicated in dyslipidemia insulin resistance, and inflammation. These include 122 metabolites: amino acids, lipids, nucleotides, vitamins, bile acids, flavonoids, xenobiotics, and carbohydrates. Hepatic amino acids, B‐vitamins, and bile acids are inversely correlated with biomarkers of insulin resistance, liver injury, steatosis, and inflammation. Further, phosphatidylcholine metabolites are positively correlated with biomarkers of liver injury and NFκB inflammation. Thirteen catechin metabolites are identified in livers of GTE‐treated mice, mostly as phase II conjugates of parental catechins or microbial‐derived valerolactones. Conclusion The defined anti‐inflammatory/metabolic interactions advance an understanding of the mechanism by which GTE catechins protect against NFκB‐mediated liver injury in NASH.