L-cysteine suppresses ghrelin and reduces appetite in rodents and humans

BACKGROUND: High-protein diets promote weight loss and subsequent weight maintenance, but are difficult to adhere to. The mechanisms by which protein exerts these effects remain unclear. However, the amino acids produced by protein digestion may have a role in driving protein-induced satiety. METHODS: We tested the effects of a range of amino acids on food intake in rodents and identified L-cysteine as the most anorexigenic. Using rodents we further studied the effect of L-cysteine on food intake, behaviour and energy expenditure. We proceeded to investigate its effect on neuronal activation in the hypothalamus and brainstem before investigating its effect on gastric emptying and gut hormone release. The effect of L-cysteine on appetite scores and gut hormone release was then investigated in humans. RESULTS: L-Cysteine dose-dependently decreased food intake in both rats and mice following oral gavage and intraperitoneal administration. This effect did not appear to be secondary to behavioural or aversive side effects. L-Cysteine increased neuronal activation in the area postrema and delayed gastric emptying. It suppressed plasma acyl ghrelin levels and did not reduce food intake in transgenic ghrelin-overexpressing mice. Repeated L-cysteine administration decreased food intake in rats and obese mice. L-Cysteine reduced hunger and plasma acyl ghrelin levels in humans. CONCLUSIONS: Further work is required to determine the chronic effect of L-cysteine in rodents and humans on appetite and body weight, and whether L-cysteine contributes towards protein-induced satiety.