Epigallocatechin gallate but not catechin prevents nonalcoholic steatohepatitis in mice similar to green tea extract while differentially affecting the gut microbiota

Abstract

Catechin-rich green tea extract (GTE) protects against nonalcoholic steatohepatitis (NASH) by alleviating gut-derived endotoxin translocation and hepatic Toll-like receptor-4 (TLR4)–nuclear factor κB (NFκB) inflammation. We hypothesized that intact GTE would attenuate NASH-associated responses along the gut–liver axis to a greater extent than purified (−)-epigallocatechin gallate (EGCG) or (+)-catechin (CAT). Male C57BL/6J mice were fed a low-fat diet, a high-fat (HF) diet, or the HF diet with 2% GTE, 0.3% EGCG or 0.3% CAT for 8 weeks prior to assessing NASH relative to endotoxemia, hepatic and intestinal inflammation, intestinal tight junction proteins (TJPs) and gut microbial ecology. GTE prevented HF-induced obesity to a greater extent than EGCG and CAT, whereas GTE and EGCG more favorably attenuated insulin resistance. GTE, EGCG and CAT similarly attenuated serum alanine aminotransferase and serum endotoxin, but only GTE and EGCG fully alleviated HF-induced NASH. However, hepatic TLR4/NFκB inflammatory responses that were otherwise increased in HF mice were similarly attenuated by GTE, EGCG and CAT. Each treatment also similarly prevented the HF-induced loss in expression of intestinal TJPs and hypoxia inducible factor-1α and the otherwise increased levels of ileal and colonic TNFα mRNA and fecal calprotectin protein concentrations. Gut microbial diversity that was otherwise lowered in HF mice was maintained by GTE and CAT only. Further, microbial metabolic functions were more similar between GTE and CAT. Collectively, GTE catechins similarly protect against endotoxin–TLR4–NFκB inflammation in NASH, but EGCG and CAT exert differential prebiotic and antimicrobial activities suggesting that catechin-mediated shifts in microbiota composition are not entirely responsible for their benefits along the gut–liver axis.