Engstler Anna Janina, Sellmann Cathrin, Jin Cheng Jun, Brandt Annette, Herz Kathleen, Priebs Josephine, Bergheim Ina
Institute of Nutrition, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University of Jena, Jena, Germany.
Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria.
Mol Nutr Food Res. 2017 May;61(5). doi: 10.1002/mnfr.201600985. Epub 2017 Feb 22.
The role of invariant natural killer T cells in the development of nonalcoholic steatohepatitis (NASH) has not yet been fully understood. Here, the effect of the invariant natural killer T-cell activator alpha-galactosylceramide (αGalCer) on the development of nonalcoholic fatty liver disease and intestinal barrier function was assessed in a mouse model of early Western-style diet (WSD) induced NASH.
Female C57BL/6J mice were either fed a liquid control diet or a liquid fructose-enriched WSD for 6 wk while being treated three times weekly with αGalCer (2 μg intraperitoneal) or vehicle. Indices of liver damage, glucose metabolism, and intestinal permeability were measured. Treatment with αGalCer markedly suppressed hepatic fat accumulation and inflammation while not affecting fasting glucose. The protective effects of αGalCer were associated with a protection against the increased translocation of bacterial endotoxins and the decreased protein levels of tight junction proteins occludin and zonula occludens 1 found in vehicle-treated mice while being fed a WSD.
Taken together, our data suggest that the protective effects of αGalCer against the development of a diet-induced NASH in mice are associated with a protection against the increased translocation of intestinal bacterial endotoxins associated with the development of NASH.
不变自然杀伤T细胞在非酒精性脂肪性肝炎（NASH）发生发展中的作用尚未完全明确。在此，我们在早期西式饮食（WSD）诱导的NASH小鼠模型中评估了不变自然杀伤T细胞激活剂α-半乳糖神经酰胺（αGalCer）对非酒精性脂肪性肝病发展及肠道屏障功能的影响。
雌性C57BL/6J小鼠分别给予液体对照饮食或富含果糖的液体WSD，持续6周，同时每周三次腹腔注射αGalCer（2μg）或溶剂。检测肝损伤、糖代谢及肠道通透性指标。αGalCer治疗显著抑制了肝脏脂肪堆积和炎症，同时不影响空腹血糖。αGalCer的保护作用与防止细菌内毒素转运增加以及防止在给予WSD的溶剂处理小鼠中发现的紧密连接蛋白闭合蛋白和闭合小带蛋白1的蛋白质水平降低有关。
综上所述，我们的数据表明，αGalCer对小鼠饮食诱导的NASH发展的保护作用与防止与NASH发展相关的肠道细菌内毒素转运增加有关。
