Melanocortin-3 receptor expression in AgRP neurons is required for normal activation of the neurons in response to energy deficiency.
AgRP
CP: Metabolism
CP: Neuroscience
fasting
food intake
ghrelin
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
31 10 2023
31 10 2023
Historique:
received:
06
04
2023
revised:
14
08
2023
accepted:
14
09
2023
medline:
6
11
2023
pubmed:
4
10
2023
entrez:
4
10
2023
Statut:
ppublish
Résumé
The melanocortin-3 receptor (MC3R) is a negative regulator of the central melanocortin circuitry via presynaptic expression on agouti-related protein (AgRP) nerve terminals, from where it regulates GABA release onto secondary MC4R-expressing neurons. However, MC3R knockout (KO) mice also exhibit defective behavioral and neuroendocrine responses to fasting. Here, we demonstrate that MC3R KO mice exhibit defective activation of AgRP neurons in response to fasting, cold exposure, or ghrelin while exhibiting normal inhibition of AgRP neurons by sensory detection of food in the ad libitum-fed state. Using a conditional MC3R KO model, we show that the control of AgRP neuron activation by fasting and ghrelin requires the specific presence of MC3R within AgRP neurons. Thus, MC3R is a crucial player in the responsiveness of the AgRP soma to both hormonal and neuronal signals of energy need.
Identifiants
pubmed: 37792535
pii: S2211-1247(23)01200-7
doi: 10.1016/j.celrep.2023.113188
pii:
doi:
Substances chimiques
Agouti-Related Protein
0
Receptor, Melanocortin, Type 3
0
Ghrelin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
113188Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK126715
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK101357
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests R.D.C., P.S., and the University of Michigan have equity in Courage Therapeutics, and R.D.C. serves on the board of the company. R.D.C. and P.S. have patents filed related to drug development based on the MC3R.