Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function.
Journal
Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592
Informations de publication
Date de publication:
29 Apr 2024
29 Apr 2024
Historique:
received:
16
08
2022
accepted:
25
03
2024
medline:
30
4
2024
pubmed:
30
4
2024
entrez:
29
4
2024
Statut:
aheadofprint
Résumé
Promoting brown adipose tissue (BAT) activity innovatively targets obesity and metabolic disease. While thermogenic activation of BAT is well understood, the rheostatic regulation of BAT to avoid excessive energy dissipation remains ill-defined. Here, we demonstrate that adenylyl cyclase 3 (AC3) is key for BAT function. We identified a cold-inducible promoter that generates a 5' truncated AC3 mRNA isoform (Adcy3-at), whose expression is driven by a cold-induced, truncated isoform of PPARGC1A (PPARGC1A-AT). Male mice lacking Adcy3-at display increased energy expenditure and are resistant to obesity and ensuing metabolic imbalances. Mouse and human AC3-AT are retained in the endoplasmic reticulum, unable to translocate to the plasma membrane and lack enzymatic activity. AC3-AT interacts with AC3 and sequesters it in the endoplasmic reticulum, reducing the pool of adenylyl cyclases available for G-protein-mediated cAMP synthesis. Thus, AC3-AT acts as a cold-induced rheostat in BAT, limiting adverse consequences of cAMP activity during chronic BAT activation.
Identifiants
pubmed: 38684889
doi: 10.1038/s42255-024-01033-8
pii: 10.1038/s42255-024-01033-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))
ID : 675014
Organisme : EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))
ID : PROTEOFIT
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : 33444
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : 28416
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : 33444
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : 28416
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : 33444
Organisme : Deutscher Akademischer Austauschdienst (German Academic Exchange Service)
ID : A/12/97620
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : TRR333/1 (450149205)
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : TRR333/1 (450149205)
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : TRR333/1 (450149205)
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB 1454 (432325352)
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : TRR83
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SPP1926
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SPP1726
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : FOR2743
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB1123-B10
Organisme : European Molecular Biology Organization (EMBO)
ID : 676-2021
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
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