Hepatoprotection by Green Tea Extract Along the Gut-liver Axis in Mice with Nonalcoholic Steatohepatitis Is Mediated by Epigallocatechin Gallate but Not Catechin (OR34-03-19)

Abstract

ObjectivesGreen tea extract (GTE) alleviates nonalcoholic steatohepatitis (NASH) through a mechanism involving the gut-liver axis by limiting endotoxin-TLR4-NFκB inflammation, but the independent bioactivities of specific green tea catechins have not been defined. We hypothesized that epigallocatechin gallate (EGCG) and catechin (CAT) would protect against NASH, but to a lesser extent than GTE. MethodsMale, 6-wk old C57BL6/J mice were provided a diet formulated to be low-fat (LF), high-fat (HF), or HF containing GTE (2%), EGCG (0.3%), or CAT (0.3%) for 8-wk. Then, NASH, endotoxin-TLR4-NFκB inflammation, and gut health were assessed. EGCG was supplemented equivalent to that in GTE, whereas CAT was matched to EGCG to evaluate their relative bioactivities. ResultsHF-feeding induced NASH in association with increased adiposity, serum endotoxin and hepatic TLR4/NFκB inflammation. HF-fed mice also had lower expression of ileal and colonic hypoxia inducible factor-1α (HIF-1α) and tight junction proteins (TJPs) whereas fecal calprotectin and the Firmicutes: Bacteroidetes (F: B) ratio were increased. Relative to HF controls, EGCG and CAT attenuated adiposity, which was further lowered by GTE. NASH (steatosis, ballooning) was attenuated by GTE, EGCG, and CAT, but only GTE and EGCG normalized liver pathology to that of LF controls. Serum endotoxin and hepatic TLR4/NFκB inflammation were similarly attenuated by GTE, EGCG and CAT. Each treatment also similarly maintained mRNA expression of ileal and colonic HIF-1α and TJPs, and attenuated fecal calprotectin and the F: B ratio. ConclusionsEGCG and CAT protected against gut barrier dysfunction and endotoxin-TLR4-NFκB inflammation similar to GTE, whereas EGCG but not CAT lowered NASH pathology similar to GTE. Although EGCG and CAT independently protect against NASH-associated inflammation, GTE bioactivities are likely attributed primarily to EGCG. Funding SourcesUSDA-NIFA and OSU Center for Applied Plant Sciences.