Green tea extract prevents obesity in male mice by alleviating gut dysbiosis in association with improved intestinal barrier function that limits endotoxin translocation and adipose inflammation

Gut-derived endotoxin translocation provokes obesity by inducing TLR4/NF kappa B inflammation. We hypothesized that catechin-rich green tea extract (GTE) would protect against obesity-associated TLR4/NF kappa B inflammation by alleviating gut dysbiosis and limiting endotoxin translocation. Male C57BL/6J mice were fed a low-fat (IF) or high-fat (HF) diet containing 0% or 2% GTE for 8 weeks. At Week 7, fluorescein isothiocyanate (FITC)-dextran was administered by oral gavage before assessing its serum concentrations as a gut permeability marker. HF-feeding increased (P<.05) adipose mass and adipose expression of genes involved in TLR4/NF kappa B-dependent inflammation and macrophage activation. GTE attenuated HF-induced obesity and pro-inflammatory gene expression. GTE in HF mice decreased serum FITC-dextran, and attenuated portal vein and circulating endotoxin concentrations. GTE in HF mice also prevented HF-induced decreases in the expression of intestinal tight junction proteins (TJPs) and hypoxia inducible factor-l alpha while preventing increases in TLR4/NF kappa B-dependent inflammatory genes. Gut microbial diversity was increased, and the Firmicutes:Bacteroidetes ratio was decreased, in HF mice fed GTE compared with HF controls. GTE in LF mice did not attenuate adiposity but decreased endotoxin and favorably altered several gut bacterial populations. Serum FITC-dextran was correlated with portal vein endotoxin (P<.001; r(p)= 0.66) and inversely correlated with colonic mRNA levels of TJPs (P<.05; r(p)= -038 to -0.48). Colonic TJPs mRNA were inversely correlated with portal endotoxin (P<.05; rp= -033 to -039). These data suggest that GTE protects against dietinduced obesity consistent with a mechanism involving the gut-adipose axis that limits endotoxin translocation and consequent adipose TLR4/NF kappa B inflammation by improving gut barrier function. (C) 2019 Elsevier Inc. All rights reserved.