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
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

2745

Subventions

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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Auteurs

Calvin C Chan (CC)

Medical Scientist Training Program, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
Immunology Graduate Program, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.

Michelle S M A Damen (MSMA)

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

Maria E Moreno-Fernandez (ME)

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

Traci E Stankiewicz (TE)

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

Monica Cappelletti (M)

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
Divisions of Neonatology and Developmental Biology, David Geffen School of Medicine at UCLA, Mattel Children's Hospital UCLA, Los Angeles, CA, USA.

Pablo C Alarcon (PC)

Medical Scientist Training Program, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
Immunology Graduate Program, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.

Jarren R Oates (JR)

Immunology Graduate Program, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.

Jessica R Doll (JR)

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

Rajib Mukherjee (R)

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

Xiaoting Chen (X)

The Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

Rebekah Karns (R)

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

Matthew T Weirauch (MT)

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA.
The Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
Divsion of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

Michael A Helmrath (MA)

Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
Center for Stem Cell & Organoid Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

Thomas H Inge (TH)

Department of Surgery, Children's Hospital Colorado, Aurora, CO, 80045, USA.

Senad Divanovic (S)

Medical Scientist Training Program, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA. senad.divanovic@cchmc.org.
Immunology Graduate Program, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA. senad.divanovic@cchmc.org.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45220, USA. senad.divanovic@cchmc.org.
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA. senad.divanovic@cchmc.org.
Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA. senad.divanovic@cchmc.org.

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