Acute L-Leucine Supplementation and Sprint Exercise Elicit Distinct Appetite and Inflammatory Responses in Persons with Overweight: A Randomized, Counterbalanced, and Crossover Design Study

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Abstract

Objectives: Our objective was to evaluate the acute effect of L-leucine supplementation and high-intensity sprint exercise on appetite-controlling neuropeptides and their association with the subjective perception of appetite (SPA), satiety (SPS), food intake, and inflammatory response in overweight participants. Methods: In a double-masked, randomized, counterbalanced, and crossover design, 12 sedentary overweight adult men performed four experiments: (1) exercise and L-leucine (EX-Leu), (2) exercise and placebo (EX-PLA), (3) L-leucine without exercise (SED-Leu), and (4) placebo without exercise (SED-PLA). The supplementation consisted of three daily doses of 70 mg/kg body weight of L-leucine or placebo (on the day of exercise and one day after). During the experiments, we recorded the food intake, SPA, and SPS, and evaluated the neuropeptides (GLP-1, PYY, CCK, and ghrelin) and cytokines (IL1-beta, IL-6, IL-10, and TNF-α) in peripheral blood. The acute exercise trial consisted of four sets of 30 sec cycle ergometer sprint exercises. Results: EX-Leu, EX-PLA, and SED-Leu decreased SPA, compared to SED-PLA; only EX-PLA improved SPS; EX-PLA and EX-Leu reduced food intake. GLP-1 decreased in the EX-PLA trial compared to SED-Leu. IL-6 and IL1-β levels increased in the EX-Leu trial compared to SED-PLA. An anti-inflammatory profile was identified in the EX-PLA trial compared to the other trials. Both neuropeptides (increased) and cytokines (a pro-inflammatory profile) were associated with changes in SPA, SPS, and food intake. Conclusions: The acute inflammatory balance induced by EX-Leu seems to improve appetite control. Sprint exercise had a consistent acute anorexic effect, while isolated L-leucine decreased SPA, but their impact on SPS and food intake is not clear (FAPESP grants: 2020/09936-2 and 2021/03601-1).

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França, E. de, Thomatieli-Santos, R. V., Aquino, R. de C., Cavalcante, M. M., Salvalágio, B. R., Hofmann, P., … Caperuto, E. das C. (2026). Acute L-Leucine Supplementation and Sprint Exercise Elicit Distinct Appetite and Inflammatory Responses in Persons with Overweight: A Randomized, Counterbalanced, and Crossover Design Study. Nutrients , 18(4). https://doi.org/10.3390/nu18040614

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