Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Dornburger Str. 29, 07743, Jena, Germany.
Nutrition Biology Laboratory EA4466, Faculty of Pharmacy, Paris Descartes University, Sorbonne Paris Cité, Paris, France.
Eur J Nutr. 2017 Dec;56(8):2519-2527. doi: 10.1007/s00394-016-1287-9. Epub 2016 Aug 5.
Impairments of intestinal barrier function are discussed as risk factors for the development and progression of non-alcoholic fatty liver disease (NAFLD). Studies suggest an association between arginine/citrulline homeostasis and the development of liver damages. Here, the effect of an oral L-citrulline (Cit) supplement on the development of a Western-style diet (WSD)-induced NAFLD was determined in mice.
Female 6- to 8-week-old C57BL/6J mice were either pair-fed a liquid Western-style or control diet (C) ± 2.5 g/kg bodyweight Cit for 6 weeks (C + Cit or WSD + Cit). Indices of liver damage, glucose metabolism, intestinal barrier function and NO synthesis were measured.
While bodyweight gain was similar between groups, markers of glucose metabolism like fasting blood glucose and HOMA index and markers of liver damage like hepatic triglyceride levels, number of neutrophils and plasminogen activator inhibitor-1 protein levels were significantly lower in WSD + Cit-fed mice when compared to WSD-fed mice only. Protein levels of the tight junction proteins occludin and zonula occludens-1 in duodenum were significantly lower in mice fed a WSD when compared to those fed a WSD + Cit (-70 and -60 %, respectively, P < 0.05), whereas portal endotoxin levels, concentration of 3-nitrotyrosine protein adducts in duodenum and toll-like receptor-4 mRNA expression in livers of WSD + Cit-fed mice were markedly lower than in WSD-fed mice (-43 %, P = 0.056; -80 and -~48 %, respectively, P < 0.05).
Our data suggest that the protective effects of supplementing Cit on the development of NAFLD in mice are associated with a decreased translocation of endotoxin into the portal vein.
肠道屏障功能障碍被认为是非酒精性脂肪性肝病（NAFLD）发生和发展的危险因素。有研究表明精氨酸/瓜氨酸稳态与肝损伤的发展之间存在关联。在此，研究人员在小鼠中确定了口服 L-瓜氨酸（Cit）补充剂对西式饮食（WSD）诱导的非酒精性脂肪性肝病发展的影响。
将 6 至 8 周龄的雌性 C57BL/6J 小鼠进行等热量喂养，分别给予液体西式饮食或对照饮食（C）±2.5 g/kg 体重 Cit 喂养 6 周（C+Cit 或 WSD+Cit）。测量肝损伤、葡萄糖代谢、肠道屏障功能和一氧化氮合成的指标。
虽然各组的体重增加相似，但 WSD+Cit 喂养组的空腹血糖和 HOMA 指数等葡萄糖代谢标志物以及肝甘油三酯水平、中性粒细胞数量和纤溶酶原激活物抑制剂-1 蛋白水平等肝损伤标志物均显著低于 WSD 喂养组。与 WSD 喂养组相比，WSD+Cit 喂养组小鼠十二指肠中紧密连接蛋白 occludin 和 zonula occludens-1 的蛋白水平显著降低（分别降低约 70%和 60%，P<0.05），而 WSD+Cit 喂养组的门静脉内毒素水平、十二指肠中 3-硝基酪氨酸蛋白加合物浓度和肝脏中 toll 样受体-4 mRNA 表达均显著低于 WSD 喂养组（分别降低约 43%，P=0.056；降低约 80%和 48%，分别，P<0.05）。
我们的数据表明，Cit 补充对小鼠非酒精性脂肪性肝病发展的保护作用与内毒素向门静脉易位减少有关。
