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

Sarah N. Gartner, Fraser Aidney, Anica Klockars, Colin Prosser, Elizabeth A. Carpenter, Kiriana Isgrove, Allen S. Levine, Pawel K. Olszewski

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)278-286
Number of pages9
JournalAppetite
Volume125
DOIs
StatePublished - Jun 1 2018

Keywords

  • Amino acids
  • Food intake
  • Oxytocin
  • Tryptophan
  • c-Fos

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    Gartner, S. N., Aidney, F., Klockars, A., Prosser, C., Carpenter, E. A., Isgrove, K., Levine, A. S., & Olszewski, P. K. (2018). Intragastric preloads of L-tryptophan reduce ingestive behavior via oxytocinergic neural mechanisms in male mice. Appetite, 125, 278-286. https://doi.org/10.1016/j.appet.2018.02.015