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

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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.