The effect of L-cysteine on appetite in humans

Abstract

High protein diets suppress appetite and facilitate weight loss. However, they are difficult to adhere to. Understanding the mechanisms by which protein suppresses appetite may establish targets for more acceptable interventions to treat or prevent obesity. Receptor systems that respond to amino acids, the products of protein digestion, have been identified. However, the specific mechanisms regulating protein-induced satiety are unknown. Previous work within our laboratory 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 food intake in rodents. L-cysteine activates the CaR, the T1R1/T1R3 and the GPRC6A. A diet that includes high levels of whey protein, which contains high levels of L-cysteine, has been reported to be more satiating and to suppress circulating levels of the orexigenic hormone ghrelin to a greater extent than other types of protein in humans. Pilot studies suggested that ligands for the GPRC6A receptor can reduce food intake in rodents, and that this effect is at least partly mediated by a reduction in circulating ghrelin levels. The putative role of L-cysteine in food intake in humans was investigated. The effect of a high protein meal on circulating levels of cysteine was determined. Subsequently, the time course of changes in the circulating levels of L-cysteine following oral consumption of L-cysteine was established. Finally, the effects of different doses of cysteine on subjective assessment of appetite and acute food intake were investigated. These studies suggested that oral administration of L-cysteine at 0.04 or 0.07g/kg resulted in supraphysiological levels of L-cysteine in circulation. Oral administration of L-cysteine significantly influenced subjective markers of appetite compared to vehicle or glycine controls, but did not affect food intake. These data suggest that L-cysteine may be suitable for manipulating appetite in humans.