Hypothalamic steroid receptor coactivator-2 regulates adaptations to fasting and overnutrition.
Animals
Anxiety
/ metabolism
Disease Models, Animal
Energy Metabolism
Fasting
/ metabolism
Feeding Behavior
Forkhead Transcription Factors
/ genetics
HEK293 Cells
Humans
Hypothalamus
/ metabolism
Male
Mice, Knockout
Neurons
/ metabolism
Nuclear Receptor Coactivator 2
/ genetics
Obesity
/ genetics
Overnutrition
/ genetics
Pro-Opiomelanocortin
/ genetics
Satiety Response
Signal Transduction
Weight Gain
FoxO1
POMC
SRC-2
anxiety
electrophysiology
feeding
glucose
ion channels
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
07 12 2021
07 12 2021
Historique:
received:
23
09
2020
revised:
09
08
2021
accepted:
09
11
2021
entrez:
8
12
2021
pubmed:
9
12
2021
medline:
15
2
2022
Statut:
ppublish
Résumé
The neuroendocrine system coordinates metabolic and behavioral adaptations to fasting, including reducing energy expenditure, promoting counterregulation, and suppressing satiation and anxiety to engage refeeding. Here, we show that steroid receptor coactivator-2 (SRC-2) in pro-opiomelanocortin (POMC) neurons is a key regulator of all these responses to fasting. POMC-specific deletion of SRC-2 enhances the basal excitability of POMC neurons; mutant mice fail to efficiently suppress energy expenditure during food deprivation. SRC-2 deficiency blunts electric responses of POMC neurons to glucose fluctuations, causing impaired counterregulation. When food becomes available, these mutant mice show insufficient refeeding associated with enhanced satiation and discoordination of anxiety and food-seeking behavior. SRC-2 coactivates Forkhead box protein O1 (FoxO1) to suppress POMC gene expression. POMC-specific deletion of SRC-2 protects mice from weight gain induced by an obesogenic diet feeding and/or FoxO1 overexpression. Collectively, we identify SRC-2 as a key molecule that coordinates multifaceted adaptive responses to food shortage.
Identifiants
pubmed: 34879284
pii: S2211-1247(21)01566-7
doi: 10.1016/j.celrep.2021.110075
pmc: PMC8715676
mid: NIHMS1762848
pii:
doi:
Substances chimiques
Forkhead Transcription Factors
0
Foxi1 protein, mouse
0
Ncoa2 protein, mouse
0
Nuclear Receptor Coactivator 2
0
Pro-Opiomelanocortin
66796-54-1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
110075Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK104901
Pays : United States
Organisme : NIDDK NIH HHS
ID : P01 DK113954
Pays : United States
Organisme : NIDDK NIH HHS
ID : P01 DK059820
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK115761
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG069966
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117281
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK111436
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM135002
Pays : United States
Organisme : NIDDK NIH HHS
ID : R00 DK107008
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL153320
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES027544
Pays : United States
Organisme : NIA NIH HHS
ID : R03 AG070687
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK109934
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK101379
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK126655
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120858
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK125480
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD007857
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK119471
Pays : United States
Organisme : NICHD NIH HHS
ID : P30 HD024064
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114279
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES030285
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS108091
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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