High leucine intake reduces the concentration of hypothalamic serotonin in piglets

Leucine (Leu) and tryptophan (Trp) modulate brain regulation of appetite and satiety. Because Leu and Trp compete for transport across the blood-brain barrier, we hypothesized that interactions between these two amino acids mediate food intake and cerebral Leu and Trp availability. The interaction between Leu and Trp was tested in a two-factor study design. To this end, weaned piglets of both sexes were randomly allotted to one of four groups and received diets with either adequate Leu (standardized ileal digestible (SID) Leu: lysine (Lys) = 100%, Leu100) or high Leu (SID Leu: Lys = 300%, Leu300) and diets with SID Trp: Lys levels of 18% (Trp18) and 23% (Trp23). Piglets that received the Leu300 diet consumed, on average, 6.5% less food than pigs fed the Leu100 diet (P < 0.05). The administration of the Leu300 diet was accompanied by higher concentrations of plasma Leu (2.2-fold, P < 0.05) and hypothalamic Leu (+37%, P < 0.05) and lower hypothalamic concentrations of serotonin (P < 0.05) and Trp (P < 0.05), although the effect of Leu on hypothalamic Trp was observed only in pigs fed the Trp23 diet. Because hypothalamic serotonin and Trp concentrations positively correlated with food intake, the Leu-induced appetite suppression was probably partially due to a reduction of the cerebral Trp available for serotonin synthesis.