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

TY - JOUR

T1 - Ingested non-essential amino acids recruit brain orexin cells to suppress eating in mice

AU - Viskaitis, Paulius

AU - Arnold, Myrtha

AU - Garau, Celia

AU - Jensen, Lise T.

AU - Fugger, Lars

AU - Peleg-Raibstein, Daria

AU - Burdakov, Denis

N1 - Publisher Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

PY - 2022/4

Y1 - 2022/4

N2 - 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.

AB - 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.

KW - amino acids

KW - appetite

KW - behavior

KW - diet

KW - exploration

KW - food intake

KW - hypocretin

KW - hypothalamus

KW - orexin

UR - http://www.scopus.com/inward/record.url?scp=85129778727&partnerID=8YFLogxK

U2 - 10.1016/j.cub.2022.02.067

DO - 10.1016/j.cub.2022.02.067

M3 - Journal article

C2 - 35316652

AN - SCOPUS:85129778727

SN - 0960-9822

VL - 32

SP - 1812-1821.e4

JO - Current biology : CB

JF - Current biology : CB

IS - 8

ER -