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Dietary supplementation of epigallocatechin gallate but not catechin protects against diet-induced nonalcoholic steatohepatitis in mice to a similar extent as green tea extract

Olmstead, Bryan Dennis
http://rave.ohiolink.edu/etdc/view?acc_num=osu1559645721453613

Abstract Details

2019, Master of Science, Ohio State University, Nutrition Program, The Ohio State University.
Increases in gut permeability trigger endotoxin induced hepatic Toll-like receptor-4/nuclear factor-κB (TLR4/NFκB)-dependent inflammation that induces nonalcoholic steatohepatitis (NASH). Reports indicate catechin-rich green tea extract (GTE) protects against NASH-associated TLR4/NFκB inflammation by maintaining intestinal barrier function that limits endotoxin translocation. However, the independent bioactivities of the green tea catechins epigallocatechin gallate (EGCG) and catechin (CAT) relative to GTE along the gut-liver axis during NASH development have not been studied. Interestingly, green tea catechins have been shown to potentiate different intestinal-level benefits in vitro. Defining the benefits catechins in vivo is critical as green tea catechin composition varies due to growing conditions and maturity of tea leaves at time of harvest. I hypothesized GTE, which is rich in catechins and phytochemicals, would more effectively alleviate TLR4/NFκB-mediated inflammation compared with EGCG and CAT. To assess this hypothesis male C57BL/6J mice (6 wk) were randomized to receive either a low fat (LF) diet, high fat (HF) diet, HF + 2% GTE (w/w; HF+GTE), HF + 0.3% EGCG (w/w; HF+EGCG), or HF + 0.3% CAT (w/w; HF+CAT) for 8-wk before assessing NASH, hepatic and intestinal inflammation, and mRNA expression of intestinal TJPs. GTE was supplemented at 2%, EGCG was supplemented at 0.3% to match its proportion in GTE, and CAT was supplemented at an equivalent dose as EGCG. Post intervention, HF diet increased obesity and the histological evidence of NASH. EGCG and CAT attenuated obesity to a lesser extent than GTE. GTE, EGCG, and CAT attenuated the histological evidence of NASH relative to HF fed mice but only GTE and EGCG attenuated NASH to that of LF fed mice. GTE, EGCG, and CAT attenuated HF-mediated increases in serum endotoxin and the expression of hepatic TLR4 and NFκB activation. GTE, EGCG, and CAT prevented HF-induced decreases in the expression of the intestinal TJPS claudin-1, occludin, zonula occluden-1, and hypoxia-inducible factor-1α at the ileum and colon. GTE, EGCG, and CAT attenuated HF-mediated increases in intestinal inflammation as evidenced by decreases in TNFα expression at the ileum and colon as well as decreased fecal calprotectin levels. These data suggest EGCG has a greater hepatoprotective benefit compared to CAT despite supplementation of both catechins having similar intestinal-level benefits in preventing HF-induced decreases in intestinal TJP expression in turn protecting the mice from endotoxin mediated TLR4/NFκB-mediated hepatic inflammation. Therefore, GTE-mediated protection against NASH is likely attributed to EGCG, which attenuates metabolic endotoxemia and hepatic TLR4/NFκB inflammation by limiting intestinal barrier permeability. Data from this study will have a positive impact in future translational studies developing a critically needed anti-inflammatory dietary strategy for prophylactic treatment in at-risk NASH cohorts.
Richard Bruno (Advisor)
Martha Belury (Committee Member)
Earl Harrison (Committee Member)
126 p.
Nutrition

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Citations

  • Olmstead, B. D. (2019). Dietary supplementation of epigallocatechin gallate but not catechin protects against diet-induced nonalcoholic steatohepatitis in mice to a similar extent as green tea extract [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1559645721453613

    APA Style (7th edition)

  • Olmstead, Bryan. Dietary supplementation of epigallocatechin gallate but not catechin protects against diet-induced nonalcoholic steatohepatitis in mice to a similar extent as green tea extract. 2019. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1559645721453613.

    MLA Style (8th edition)

  • Olmstead, Bryan. "Dietary supplementation of epigallocatechin gallate but not catechin protects against diet-induced nonalcoholic steatohepatitis in mice to a similar extent as green tea extract." Master's thesis, Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1559645721453613

    Chicago Manual of Style (17th edition)

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This open access ETD is published by The Ohio State University and OhioLINK.