Ingested non-essential amino acids recruit brain orexin cells to suppress eating in mice

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  • Paulius Viskaitis, ETH Zürich
  • ,
  • Myrtha Arnold, ETH Zürich
  • ,
  • Celia Garau, University of Leicester
  • ,
  • Lise T. Jensen
  • Lars Fugger
  • Daria Peleg-Raibstein, ETH Zürich
  • ,
  • Denis Burdakov, ETH Zürich

Ingested nutrients are proposed to control mammalian behavior by modulating the activity of hypothalamic orexin/hypocretin neurons (HONs). Previous in vitro studies showed that nutrients ubiquitous in mammalian diets, such as non-essential amino acids (AAs) and glucose, modulate HONs in distinct ways. Glucose inhibits HONs, whereas non-essential (but not essential) AAs activate HONs. The latter effect is of particular interest because its purpose is unknown. Here, we show that ingestion of a dietary-relevant mix of non-essential AAs activates HONs and shifts behavior from eating to exploration. These effects persisted despite ablation of a key neural gut → brain communication pathway, the cholecystokinin-sensitive vagal afferents. The behavioral shift induced by the ingested non-essential AAs was recapitulated by targeted HON optostimulation and abolished in mice lacking HONs. Furthermore, lick microstructure analysis indicated that intragastric non-essential AAs and HON optostimulation each reduce the size, but not the frequency, of consumption bouts, thus implicating food palatability modulation as a mechanism for the eating suppression. Collectively, these results suggest that a key purpose of HON activation by ingested, non-essential AAs is to suppress eating and re-initiate food seeking. We propose and discuss possible evolutionary advantages of this, such as optimizing the limited stomach capacity for ingestion of essential nutrients.

Original languageEnglish
JournalCurrent biology : CB
Volume32
Issue8
Pages (from-to)1812-1821.e4
Number of pages10
ISSN0960-9822
DOIs
Publication statusPublished - Apr 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 Elsevier Inc. All rights reserved.

    Research areas

  • amino acids, appetite, behavior, diet, exploration, food intake, hypocretin, hypothalamus, orexin

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