Adipocyte HIF2α functions as a thermostat via PKA Cα regulation in beige adipocytes.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 06 2022
07 06 2022
Historique:
received:
19
08
2021
accepted:
24
05
2022
entrez:
7
6
2022
pubmed:
8
6
2022
medline:
10
6
2022
Statut:
epublish
Résumé
Thermogenic adipocytes generate heat to maintain body temperature against hypothermia in response to cold. Although tight regulation of thermogenesis is required to prevent energy sources depletion, the molecular details that tune thermogenesis are not thoroughly understood. Here, we demonstrate that adipocyte hypoxia-inducible factor α (HIFα) plays a key role in calibrating thermogenic function upon cold and re-warming. In beige adipocytes, HIFα attenuates protein kinase A (PKA) activity, leading to suppression of thermogenic activity. Mechanistically, HIF2α suppresses PKA activity by inducing miR-3085-3p expression to downregulate PKA catalytic subunit α (PKA Cα). Ablation of adipocyte HIF2α stimulates retention of beige adipocytes, accompanied by increased PKA Cα during re-warming after cold stimuli. Moreover, administration of miR-3085-3p promotes beige-to-white transition via downregulation of PKA Cα and mitochondrial abundance in adipocyte HIF2α deficient mice. Collectively, these findings suggest that HIF2α-dependent PKA regulation plays an important role as a thermostat through dynamic remodeling of beige adipocytes.
Identifiants
pubmed: 35672324
doi: 10.1038/s41467-022-30925-0
pii: 10.1038/s41467-022-30925-0
pmc: PMC9174489
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
MicroRNAs
0
endothelial PAS domain-containing protein 1
1B37H0967P
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
EC 2.7.11.11
protein kinase A Calpha
EC 2.7.11.11
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3268Informations de copyright
© 2022. The Author(s).
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