Oral citrulline supplementation protects female mice from the development of non-alcoholic fatty liver disease (NAFLD)
Oral citrulline supplementation protects female mice from the development of non-alcoholic fatty liver disease (NAFLD)
复制标题
DOI：
10.1007/s00394-016-1287-9
复制
发表时间：
2017-12-01
影响因子：
5
通讯作者：
Bergheim, Ina
中科院分区：
文献类型：
--
作者：
Sellmann, Cathrin;Jin, Cheng Jun;Bergheim, Ina
目的探讨肠屏障功能受损作为非酒精性脂肪性肝病（NAFLD）发生和进展的危险因素。研究表明精氨酸/瓜氨酸稳态与肝损伤的发生之间存在关联。在此，确定口服L-瓜氨酸（Cit）补充剂对西式饮食（WSD）诱导的小鼠NAFLD发展的影响。方法将6至8周龄的雌性C57 BL/6J小鼠成对喂食西式或对照饮食（C）+/-2.5 g/kg体重Cit 6周（C + Cit或WSD + Cit）。结果WSD + Cit-fed小鼠的体重增加相似，但糖代谢指标如空腹血糖、HOMA指数和肝损伤指标如肝甘油三酯水平、中性粒细胞数量和纤溶酶原激活物抑制物-1蛋白水平均显著低于WSD + Cit-fed小鼠。与喂食WSD + Cit的小鼠相比，喂食WSD的小鼠十二指肠中紧密连接蛋白occludin和闭合小带-1的蛋白水平显著降低（分别为-类似于70%和-类似于60%，P <0.05），而门静脉内毒素水平，WSD + Cit-fed小鼠的十二指肠中3-硝基酪氨酸蛋白加合物的浓度和肝脏中Toll样受体-4mRNA的表达显著低于WSD-fed小鼠结论补充Cit对NAFLD小鼠的保护作用可能与减少内毒素向门静脉的转运有关。
Purpose 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.Methods 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.Results 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 (-similar to 70 and -similar to 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 (-similar to 43 %, P = 0.056; -similar to 80 and -similar to 48 %, respectively, P < 0.05).Conclusion 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.