4.7 Article

Green tea extract protects against hepatic NF kappa B activation along the gut-liver axis in diet-induced obese mice with nonalcoholic steatohepatitis by reducing endotoxin and TLR4/MyD88 signaling

期刊

JOURNAL OF NUTRITIONAL BIOCHEMISTRY
卷 53, 期 -, 页码 58-65

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2017.10.016

关键词

Green tea; NASH; Inflammation; TLR4; Endotoxin

资金

  1. USDA-NIFA [2014-67017-21761]
  2. Ohio State University (OSU) Food Innovation Center
  3. Molecular Carcinogenesis and Chemoprevention Program of The OSU Comprehensive Cancer Center (NIH, National Cancer Institute) [P30CA16058]
  4. OSU Center for Advanced Functional Foods Research and Entrepreneurship
  5. OSU Ohio Agricultural Research and Development Center

向作者/读者索取更多资源

Green tea extract (GTE) reduces NF kappa B-mediated inflammation during nonalcoholic steatohepatitis (NASH). We hypothesized that its anti-inflammatory activities would be mediated in a Toll-like receptor 4 (TLR4)-dependent manner. Wild-type (WT) and loss-of-function TLR4-mutant (TLR4m) mice were fed a high-fat diet containing GTE at 0 or 2% for 8 weeks before assessing NASH, NF kappa B-mediated inflammation, TLR4 and its adaptor proteins MyD88 and TRIF, circulating endotoxin, and intestinal tight junction protein mRNA expression. TLR4m mice had lower (P < .05) body mass compared with WT mice but similar adiposity, whereas body mass and adiposity were lowered by GTE regardless of genotype. Liver steatosis, serum alanine aminotransferase, and hepatic lipid peroxidation were also lowered by GTE in WT mice, and were similarly lowered in TLR4m mice regardless of GTE. Phosphorylation of the NFKB p65 subunit and pro-inflammatory genes (TNF alpha, iNOS, MCP-1, MPO) were lowered by GTE in WT mice, and did not differ from the lowered levels in TLR4m mice regardless of GTE. TLR4m mice had lower TLR4 mRNA, which was also lowered by GTE in both genotypes. TRIF expression was unaffected by genotype and GTE, whereas MyD88 was lower in mice fed GTE regardless of genotype. Serum endotoxin was similarly lowered by GTE regardless of genotype. Tight junction protein mRNA levels were unaffected by genotype. However, GTE similarly increased claudin-1 mRNA in the duodenum and jejunum and mRNA levels of occludin and zonula occluden-1 in the jejunum and ileum. Thus, GTE protects against inflammation during NASH, likely by limiting gut-derived endotoxin translocation and TLR4/MyD88/NF kappa B activation. (C) 2017 Elsevier Inc. All rights reserved.

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