Type I interferon sensing unlocks dormant adipocyte inflammatory potential.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 06 2020
02 06 2020
Historique:
received:
07
12
2019
accepted:
12
05
2020
entrez:
4
6
2020
pubmed:
4
6
2020
medline:
22
8
2020
Statut:
epublish
Résumé
White adipose tissue inflammation, in part via myeloid cell contribution, is central to obesity pathogenesis. Mechanisms regulating adipocyte inflammatory potential and consequent impact of such inflammation in disease pathogenesis remain poorly defined. We show that activation of the type I interferon (IFN)/IFNα receptor (IFNAR) axis amplifies adipocyte inflammatory vigor and uncovers dormant gene expression patterns resembling inflammatory myeloid cells. IFNβ-sensing promotes adipocyte glycolysis, while glycolysis inhibition impeded IFNβ-driven intra-adipocyte inflammation. Obesity-driven induction of the type I IFN axis and activation of adipocyte IFNAR signaling contributes to obesity-associated pathogenesis in mice. Notably, IFNβ effects are conserved in human adipocytes and detection of the type I IFN/IFNAR axis-associated signatures positively correlates with obesity-driven metabolic derangements in humans. Collectively, our findings reveal a capacity for the type I IFN/IFNAR axis to regulate unifying inflammatory features in both myeloid cells and adipocytes and hint at an underappreciated contribution of adipocyte inflammation in disease pathogenesis.
Identifiants
pubmed: 32488081
doi: 10.1038/s41467-020-16571-4
pii: 10.1038/s41467-020-16571-4
pmc: PMC7265526
doi:
Substances chimiques
IFNAR1 protein, human
0
Interferon Type I
0
Receptor, Interferon alpha-beta
156986-95-7
Interferon-beta
77238-31-4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2745Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK078392
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM063483
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI118697
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK099222
Pays : United States
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