Effects of an oral supplementation of arginine, citrulline and glutamine on the development and progression of non-alcoholic fatty liver disease (NAFLD): Role of gender and age

非酒精性脂肪性肝病（NAFLD）的患病率显著增加，目前NAFLD是世界范围内最常见的肝病之一，但仍缺乏公认的、成功的治疗方法。研究表明，即使是NAFLD的早期阶段也与肠内细菌内毒素的肠移位增加和肝脏中Toll样受体（TLR）依赖性信号通路的诱导有关。第一个资助期使用动物模型的结果表明，口服补充精氨酸、瓜氨酸或谷氨酰胺对NAFLD的发展具有保护作用。我们的数据进一步表明，这三种氨基酸之间的机制有显著差异。口服补充氨基酸是否对NAFLD的进展也有治疗作用尚未明确。因此，本研究的目的是（1）进一步阐明精氨酸保护作用的机制，瓜氨酸和谷氨酰胺对小鼠NAFLD发展的影响，特别关注肝脏脂肪酸分布和肠道微生物群的变化，以及（2）以确定这三种氨基酸是否对小鼠的疾病也具有治疗作用，从而也旨在增加新的prevention预防and therapeutic治疗strategies策略.

The prevalence of non-alcoholic fatty liver disease (NAFLD) hasmarkedly increased and by now NAFLD is one of the most frequentliver diseases worldwide; however, universally accepted, successfultherapies are still lacking. Studies indicate that even early stages ofNAFLD are associated with an increased intestinal translocation ofbacterial endotoxin in the intestine and an induction of toll-likereceptor (TLR)-dependent signaling pathways in the liver. Results ofthe first funding period using animal models suggest that an oralsupplementation of arginine, citrulline or glutamine possess protectiveeffects on the development of NAFLD. Our data further suggest thatthe mechanisms involved herein markedly differ between the threeamino acids. If an oral supplementation of the amino acids alsopossess therapeutic effects on the progression of NAFLD has not yetbeen clarified. Therefore, the aim of the present research project is (1)to further delineate the mechanisms involved in the protective effectsof arginine, citrulline and glutamine on the development of NAFLD inmice with a special focus on changes in hepatic fatty acid distributionand intestinal microbiota and (2) to determine if the three amino acidsalso possess therapeutic effects on the disease in mice thereby alsoaiming to add to the development of new prevention and therapeuticstrategies.