Jegatheesan Prasanthi, Beutheu Stéphanie, Freese Kim, Waligora-Dupriet Anne-Judith, Nubret Esther, Butel Marie-Jo, Bergheim Ina, De Bandt Jean-Pascal
1EA4466, Faculty of Pharmacy,Paris Descartes University,Sorbonne Paris Cité,75006 Paris,France.
2EA4065, Faculty of Pharmacy,Paris Descartes University,Sorbonne Paris Cité,75006 Paris,France.
Br J Nutr. 2016 Jul;116(2):191-203. doi: 10.1017/S0007114516001793. Epub 2016 May 20.
A Western diet induces insulin resistance, liver steatosis (non-alcoholic fatty liver disease (NAFLD)) and intestinal dysbiosis, leading to increased gut permeability and bacterial translocation, thus contributing to the progression of NAFLD to non-alcoholic steatohepatitis. In the present study, we sought, in a model of Western diet-induced NAFLD, to determine whether citrulline (Cit), an amino acid that regulates protein and energy metabolism, could decrease Western diet-induced liver injuries, as well as the mechanisms involved. Sprague-Dawley rats were fed a high-fat diet (45 %) and fructose (30 %) in drinking water or a control diet associated with water (group C) for 8 weeks. The high-fat, high-fructose diet (Western diet) was fed either alone (group WD) or with Cit (1 g/kg per d) (group WDC) or an isonitrogenous amount of non-essential amino acids (group WDA). We evaluated nutritional and metabolic status, liver function, intestinal barrier function, gut microbiota and splanchnic inflammatory status. Cit led to a lower level of hepatic TAG restricted to microvesicular lipid droplets and to a lower mRNA expression of CCAAT-enhancer-binding protein homologous protein, a marker of endoplasmic reticulum stress, of pro-inflammatory cytokines Il6 (P<0·05) and Tnfα, and of toll-like receptor 4 (Tlr4) (P<0·05). Cit also improved plasma TAG and insulin levels. In the colon, it decreased inflammation (Tnfα and Tlr4 expressions) and increased claudin-1 protein expression. This was associated with higher levels of Bacteroides/Prevotella compared with rats fed the Western diet alone. Cit improves Western diet-induced liver injuries via decreased lipid deposition, increased insulin sensitivity, lower inflammatory process and preserved antioxidant status. This may be related in part to its protective effects at the gut level.
西式饮食会引发胰岛素抵抗、肝脂肪变性（非酒精性脂肪性肝病（NAFLD））和肠道菌群失调，导致肠道通透性增加和细菌易位，从而促使NAFLD进展为非酒精性脂肪性肝炎。在本研究中，我们在西式饮食诱导的NAFLD模型中，探究调节蛋白质和能量代谢的氨基酸瓜氨酸（Cit）是否能够减轻西式饮食诱导的肝损伤及其相关机制。将斯普拉格-道利大鼠分为三组，分别给予高脂肪饮食（45%）并饮用含果糖（30%）的水、对照组饮食并饮用普通水（C组），持续8周。其中，高脂肪、高果糖饮食组（西式饮食组，WD组）单独给予该饮食，高脂肪、高果糖饮食 + 瓜氨酸组（WDC组）给予含Cit（1 g/kg每日）的相同饮食，高脂肪、高果糖饮食 + 等氮量非必需氨基酸组（WDA组）给予含等氮量非必需氨基酸的相同饮食。我们评估了营养和代谢状况、肝功能、肠道屏障功能、肠道微生物群和内脏炎症状态。结果显示，Cit可使肝内甘油三酯（TAG）水平降低，且仅限于微泡脂质滴，同时CCAAT增强子结合蛋白同源蛋白（内质网应激标志物）、促炎细胞因子Il6（P<0·05）、Tnfα以及Toll样受体4（Tlr4）（P<0·05）的mRNA表达水平也降低。此外，Cit还改善了血浆TAG和胰岛素水平。在结肠中，它减轻了炎症（Tnfα和Tlr4表达）并增加了紧密连接蛋白-1的蛋白表达。与单独喂食西式饮食的大鼠相比，这与拟杆菌属/普雷沃菌属水平升高有关。Cit通过减少脂质沉积、提高胰岛素敏感性、降低炎症反应和维持抗氧化状态，改善了西式饮食诱导的肝损伤。这可能部分与其在肠道水平的保护作用有关。
