Catechin‐Rich Green Tea Extract and the Loss‐of‐TLR4 Signaling Differentially Alter the Hepatic Metabolome in Mice with Nonalcoholic Steatohepatitis

Abstract

Scope Catechin‐rich green tea extract (GTE) limits inflammation in nonalcoholic steatohepatitis (NASH) consistent with a Toll‐like receptor 4 (TLR4)‐dependent mechanism. It is hypothesized that GTE supplementation during NASH will shift the hepatic metabolome similar to that attributed to the loss‐of‐TLR4 signaling. Methods and results Wild‐type (WT) and loss‐of‐function TLR4‐mutant (TLR4mut) mice are fed a high‐fat diet containing 0% or 2% GTE for 8 weeks prior to performing untargeted mass spectrometry‐based metabolomics on liver tissue. The loss‐of‐TLR4 signaling and GTE shift the hepatic metabolome away from that of WT mice. However, relatively few metabolites are altered by GTE in WT mice to the same extent as the loss‐of‐TLR4 signaling in TLR4mut mice. GTE increases acetyl‐coenzyme A precursors and spermidine to a greater extent than the loss‐of‐TLR4 signaling. Select metabolites associated with thiol metabolism are similarly affected by GTE and the loss‐of‐TLR4 signaling. Glycerophospholipid catabolites are decreased by GTE, but are unaffected in TLR4mut mice. Conversely, the loss‐of‐TLR4 signaling but not GTE increases several bile acid metabolites. Conclusion GTE limitedly alters the hepatic metabolome consistent with a TLR4‐dependent mechanism. This suggests that the anti‐inflammatory activities of GTE and loss‐of‐TLR4 signaling that regulate hepatic metabolism to abrogate NASH are likely due to distinct mechanisms.

Systemic and Ocular Anti-Inflammatory Mechanisms of Green Tea Extract on Endotoxin-Induced Ocular Inflammation

“…In our metabolomic study, GTE alone was not used as a control because it affects many metabolic pathways (61). This study aimed to investigate the underlying metabolic mechanisms how GTE can resolve the inflammation induced by LPS, so GTE with LPS served as treatment controls while LPS as a positive control.…”

Naringenin prevents non‐alcoholic steatohepatitis by modulating the host metabolome and intestinal microbiome in MCD diet‐fed mice

“…Quercetin, which is the most reported polyphenol, has been demonstrated to ameliorate NAFLD in mice via regulating gut microbiota ( Akkermansia , Bifidobacterium , and Lactobacillus ) and altering the host fatty acid metabolism (Shi et al, 2022 ). Catechin can alleviate NASH by altering the host hepatic metabolome (Sasaki et al, 2021 ). Epigallocatechin gallate, also an antioxidant polyphenol, prevents NASH by affecting the gut microbiota (Dey et al, 2020 ).…”