Obesity is the leading cause of mortality and morbidity in the world. There is a clear lack of safe and effective treatments for obesity. Dieting and exercise remain the most effective treatment strategy, but are difficult to adhere to. High protein diets have proven to promote satiation and weight loss, and to facilitate subsequent weight maintenance. The mechanism by which high protein diets exert their effect is unclear. Evidence suggests that amino acids produced by protein digestion may play a role in satiety and appetite regulation.

We tested the effect of various amino acids on gut hormone release in a mice primary colonic L-cells model and found L-arginine to be a potent  stimulus of glucagon-like peptide 1 (GLP-1) and peptide tyrosine tyrosine (PYY) release from these cells. L-arginine significantly reduced food intake following oral and intraperitoneal administration in both mice and rats in a dose dependent manner. This effect did not appear to be secondary to behavioural side effects. L-arginine had no significant effect on energy expenditure in mice as assessed by measuring oxygen consumption (VO₂) using the Comprehensive Lab Animal Monitoring System. Oral administration of L-arginine significantly elevated plasma GLP-1 and PYY levels in rats. Central administration of L-arginine did not reduce food intake in rats, suggesting that its effects on appetite are peripherally mediated. L-arginine may therefore contribute towards protein-induced satiety by promoting the release of anorectic gut hormones GLP-1 and PYY, and the L-arginine sensing system may represent a possible target for anti-obesity agents.

Conflicts of interest: The authors declare no conflicts of interest.

Sources of research support: The Section is funded by grants from the BBSRC (BB/I001816/1), MRC, NIHR, Wellcome Trust an Integrative Mammalian Biology (IMB) Capacity Building Award, an FP7- HEALTH- 2009- 241592 EurOCHIP grant, NC3R’s, Technology Strategy Board and the Society for Endocrinology.