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Epigallocatechin gallate but not catechin prevents nonalcoholic steatohepatitis in mice similar to green tea extract while differentially affecting the gut microbiota.
The Journal of Nutritional Biochemistry ( IF 4.8 ) Pub Date : 2020-06-20 , DOI: 10.1016/j.jnutbio.2020.108455
Priyankar Dey 1 , Bryan D Olmstead 2 , Geoffrey Y Sasaki 2 , Yael Vodovotz 3 , Zhongtang Yu 4 , Richard S Bruno 2
Affiliation  

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.



中文翻译:

表没食子儿茶素没食子酸酯而不是儿茶素能预防类似于绿茶提取物的小鼠非酒精性脂肪性肝炎,同时差异性地影响肠道菌群。

富含儿茶素的绿茶提取物(GTE)通过减轻肠道来源的内毒素易位和肝Toll样受体4(TLR4)-核因子κB(NFκB)炎症来预防非酒精性脂肪性肝炎(NASH)。我们假设完整的GTE会比纯化的(-)-表没食子儿茶素没食子酸酯(EGCG)或(+)-儿茶素(CAT)更大程度地减弱肠-肝轴上与NASH相关的反应。在评估NASH相对于内毒素血症,肝病的NASH之前,先对雄性C57BL / 6J小鼠喂养低脂饮食,高脂(HF)饮食或含2%GTE,0.3%EGCG或0.3%CAT的HF饮食,持续8周肠道炎症,肠道紧密连接蛋白(TJP)和肠道微生物生态。与EGCG和CAT相比,GTE在更大程度上预防了由HF引起的肥胖,而GTE和EGCG更有利地减轻了胰岛素抵抗。GTE,EGCG和CAT类似地减弱了血清丙氨酸转氨酶和血清内毒素,但是只有GTE和EGCG可以完全缓解HF诱导的NASH。但是,HFTE小鼠原本会增加的肝TLR4 /NFκB炎症反应也被GTE,EGCG和CAT减弱。每种治疗还同样防止了HF诱导的肠TJPs和缺氧诱导因子1α的表达减少,以及回肠和结肠TNFαmRNA的水平升高以及粪便钙卫蛋白的浓度升高。仅通过GTE和CAT就能维持原本在HF小鼠体内肠道微生物多样性的降低。此外,GTE和CAT之间的微生物代谢功能更为相似。总的来说,GTE儿茶素在NASH中同样可以预防内毒素–TLR4 –NFκB的炎症,

更新日期:2020-06-20
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