Abstract
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 language | English |
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Journal | Current biology : CB |
Volume | 32 |
Issue number | 8 |
Pages (from-to) | 1812-1821 |
Number of pages | 10 |
ISSN | 0960-9822 |
DOIs | |
Publication status | Published - 2022 |
Bibliographical note
Publisher Copyright:Copyright © 2022 Elsevier Inc. All rights reserved.
Keywords
- amino acids
- appetite
- behavior
- diet
- exploration
- food intake
- hypocretin
- hypothalamus
- orexin