It is well established that ingested protein has a greater satiating effect than other macronutrients. The mechanisms behind this effect are unknown, although it is believed that protein induces a greater increase in levels of anorectic gut hormones than carbohydrate or fat. Recent identification of a family of promiscuous L-amino acid receptors has provided a potential mechanism for the effects of protein on appetite. These amino acid receptors - the G-protein coupled receptor family C group 6 member A (GPRC6A), the Taste receptor type 1 member 1/Taste receptor type 1 member 3 (T1R1/T1R3) dimer and the calcium-sensing receptor (CaR) - are non-specific in their ligand binding but show preference for different families of amino acids.
I assessed the effects of peripheral administration of a wide range of amino acids on food intake in rodents. My results demonstrate that the specific amino acids L-arginine, L-cysteine and L-lysine acutely reduce food intake following peripheral administration. The 0-1 hour food intake following both intraperitoneal (i.p.) and oral administration of amino acids in rats negatively correlated with the stimulatory efficacy of amino acids at the T1R1/T1R3. I subsequently investigated the mechanisms by which L-arginine, L-cysteine and L-lysine inhibit food intake. Oral administration, of L-arginine and L-lysine tended to increase levels of the anorectic hormones glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). Intraperitoneal administration of L-cysteine reduced levels of circulating total and acyl-ghrelin.
Conditioned taste aversion studies suggested that the anorectic effect of these amino acids is not secondary to visceral illness. Chronic administration of L-cysteine significantly reduces cumulative food intake. My studies suggest that specific amino acids can influence food intake, perhaps by altering circulating levels of gastrointestinal hormones. Altering dietary amino acid content may be helpful to prevent or treat obesity.