Li Jinhui, Sapper Teryn N, Mah Eunice, Moller Meredith V, Kim Joshua B, Chitchumroonchokchai Chureeporn, McDonald Joshua D, Bruno Richard S
Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA.
Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA; Biofortis, Inc., Addison, IL 60101, USA.
J Nutr Biochem. 2017 Mar;41:34-41. doi: 10.1016/j.jnutbio.2016.12.007. Epub 2016 Dec 21.
NFκB-mediated inflammation contributes to liver injury during nonalcoholic steatohepatitis (NASH). We hypothesized that antiinflammatory activities of green tea extract (GTE) during NASH would lower tumor necrosis factor receptor-1 (TNFR1)- and Toll-like receptor-4 (TLR4)-mediated NFκB activation. Male C57BL6/J mice (6 weeks old) were fed a low-fat (LF) or high-fat (HF) diet for 12 weeks to induce NASH. They were then randomized to continue on these diets supplemented with 0 or 2% GTE (n=10/group) for an additional 8 weeks prior to evaluating NASH, NFκB inflammation and TNFR1 and TLR4 receptor complexes and their respective ligands, TNFα and endotoxin. HF feeding increased (P<.05) serum alanine aminotransferase (ALT) activity and histological evidence of NASH compared with LF controls. HF-mediated increases in NFκB p65 phosphorylation were also accompanied by increased serum TNFα and endotoxin concentrations, mRNA expression of hepatic TNFR1 and TLR4 and MyD88 protein levels. GTE in LF mice had no effect (P>.05) on liver histology or inflammatory responses. However, GTE in HF mice decreased biochemical and histological parameters of NASH and lowered hepatic p65 phosphorylation in association with decreased serum TNFα, mRNA expression of TNFR1 and TLR4 and MyD88 protein. GTE in HF-fed mice also lowered serum endotoxin and up-regulated mRNA expression of duodenal occludin and zonula occluden-1 and ileal occludin and claudin-1 that were otherwise lowered in expression by HF feeding. These data suggest that dietary GTE treatment reduces hepatic inflammation in NASH by decreasing proinflammatory signaling through TNFR1 and TLR4 that otherwise increases NFκB activation and liver injury.
核因子κB（NFκB）介导的炎症在非酒精性脂肪性肝炎（NASH）期间会导致肝损伤。我们推测，NASH期间绿茶提取物（GTE）的抗炎活性会降低肿瘤坏死因子受体-1（TNFR1）和Toll样受体-4（TLR4）介导的NFκB激活。将6周龄雄性C57BL6/J小鼠喂食低脂（LF）或高脂（HF）饮食12周以诱导NASH。然后将它们随机分组，在继续这些饮食的基础上补充0%或2%的GTE（每组n = 10），再持续8周，之后评估NASH、NFκB炎症以及TNFR1和TLR4受体复合物及其各自的配体肿瘤坏死因子α（TNFα）和内毒素。与LF对照组相比，HF喂养增加了（P<0.05）血清丙氨酸氨基转移酶（ALT）活性以及NASH的组织学证据。HF介导的NFκB p65磷酸化增加还伴随着血清TNFα和内毒素浓度升高、肝脏TNFR1和TLR4的mRNA表达以及髓样分化因子88（MyD88）蛋白水平升高。LF小鼠中的GTE对肝脏组织学或炎症反应没有影响（P>0.05）。然而，HF小鼠中的GTE降低了NASH的生化和组织学参数，并降低了肝脏p65磷酸化，同时血清TNFα、TNFR1和TLR4的mRNA表达以及MyD88蛋白减少。HF喂养小鼠中的GTE还降低了血清内毒素，并上调了十二指肠闭合蛋白和紧密连接蛋白-1以及回肠闭合蛋白和紧密连接蛋白-1的mRNA表达，而这些蛋白的表达在HF喂养时会降低。这些数据表明，饮食中GTE处理通过减少经由TNFR1和TLR4的促炎信号传导来减轻NASH中的肝脏炎症，否则该信号传导会增加NFκB激活和肝损伤。
