Dietary supplementation and intragastric infusions of L-tryptophan reduce food intake

Select free amino acids have been suggested to promote early satiation. Initial studies indicate that L-tryptophan may play an important role in reducing appetite. The current set of experiments examined whether dietary and intragastrically administered L-tryptophan decreases food consumption and whether this effect is specific to eating stimulated by energy (calorie) needs or by pleasant taste (reward). A link between a satiating action of L-tryptophan and activity of the anorexigenic oxytocin circuit has also been investigated. Supplementation of milk formula-based diets with tryptophan reduced energy deprivation-induced consumption of these formulas in mice. Tryptophan enrichment had no effect on water intake, which precludes the involvement of taste- or thirst-related mechanisms in tryptophan-driven hypophagia. Intragastrically administered L-tryptophan decreased deprivation-induced chow intake. It also reduced hedonics-driven consumption of palatable saccharin and milk, but not of sucrose solutions in non-deprived mice, suggesting a link with feeding reward mechanisms unrelated to sucrose. Finally, oxytocin receptor blockade with very low doses of an antagonist just prior to intragastric L-tryptophan administration, completely abolished early termination of deprivation-induced food intake by this amino acid. Overall, the data indicate that dietary supplementation and intragastric delivery of free L-tryptophan reduce eating behaviour stimulated by energy needs and palatability, and that the effect of L-tryptophan is mediated by the anorexigenic oxytocin system

Intragastric preloads of L-tryptophan reduce ingestive behavior via oxytocinergic neural mechanisms in male mice

Human and laboratory animal studies suggest that dietary supplementation of a free essential amino acid, l-tryptophan (TRP), reduces food intake. It is unclear whether an acute gastric preload of TRP decreases consumption and whether central mechanisms underlie TRP-driven hypophagia. We examined the effect of TRP administered via intragastric gavage on energy- and palatability-induced feeding in mice. We sought to identify central mechanisms through which TRP suppresses appetite. Effects of TRP on consumption of energy-dense and energy-dilute tastants were established in mice stimulated to eat by energy deprivation or palatability. A conditioned taste aversion (CTA) paradigm was used to assess whether hypophagia is unrelated to sickness. c-Fos immunohistochemistry was employed to detect TRP-induced activation of feeding-related brain sites and of oxytocin (OT) neurons, a crucial component of satiety circuits. Also, expression of OT mRNA was assessed with real-time PCR. The functional importance of OT in mediating TRP-driven hypophagia was substantiated by showing the ability of OT receptor blockade to abolish TRP-induced decrease in feeding. TRP reduced intake of energy-dense standard chow in deprived animals and energy-dense palatable chow in sated mice. Anorexigenic doses of TRP did not cause a CTA. TRP failed to affect intake of palatable yet calorie-dilute or noncaloric solutions (10% sucrose, 4.1% Intralipid or 0.1% saccharin) even for TRP doses that decreased water intake in thirsty mice. Fos analysis revealed that TRP increases activation of several key feeding-related brain areas, especially in the brain stem and hypothalamus. TRP activated hypothalamic OT neurons and increased OT mRNA levels, whereas pretreatment with an OT antagonist abolished TRP-driven hypophagia. We conclude that intragastric TRP decreases food and water intake, and TRP-induced hypophagia is partially mediated via central circuits that encompass OT