High protein diets suppress appetite and facilitate weight loss, but are difficult to adhere to in the long-term. Understanding the mechanisms by which protein suppresses appetite may establish targets for more acceptable interventions to treat or prevent obesity. Of particular interest is the concept of functional foods or novel products which aim to potentiate satiety. However, the specific mechanisms regulating protein-induced satiety are unknown. Protein has a satiating effect greater than that of other macronutrients. A high protein meal increases circulating concentrations of the anorectic gut hormones peptide YY (PYY) and glucagon-like peptide-1 (GLP-1). The effects of a high protein diet are thought to be mediated by PYY. Receptor systems that respond to amino acids have been identified. Previous work has investigated the effect of specific amino acids which act as ligands for the following G-protein coupled receptors: CaR, T1R1/T1R3 and GPRC6A on appetite in rodents. These receptors are present within the gut, where they are thought to be responsible for amino acid sensing. L-arginine activates the T1R1/T1R3, the GPRC6A and the CaR. Animal studies showed that L-arginine can significantly reduce food intake and elevate plasma GLP-1 and PYY, whilst glycine had no effect.
The role of L-arginine on anorectic gut hormone release in humans was thus investigated. Following an overnight fast, nine healthy volunteers were given capsules containing a dose of L-arginine, glycine or vehicle control (17.1 μmol) in a double-blinded randomised manner. Following administration of the amino acid or control, visual analogue scales were completed and gut hormone analysis carried out every 15 min over a 2.5 h period. At t=60 min, an ad libitum meal was presented to the volunteers in order to assess food intake. Oral administration of L-arginine significantly increased circulating levels of GLP-1 (P<0.01) compared to vehicle or glycine controls. In addition, following the ad libitum meal there was a significant increase in PYY (P<0.05) following L-arginine administration compared to vehicle or glycine controls. However, L-arginine had no significant effect on subjective measures of appetite or food intake compared to vehicle or glycine controls. These results suggest L-arginine can modulate gut hormone release in humans.