Regulation of adipogenic differentiation and adipose tissue inflammation by interferon regulatory factor 3.
Journal
Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
15
10
2020
accepted:
26
04
2021
revised:
21
04
2021
pubmed:
7
6
2021
medline:
24
3
2022
entrez:
6
6
2021
Statut:
ppublish
Résumé
Dysfunction of adipocytes and adipose tissue is a primary defect in obesity and obesity-associated metabolic diseases. Interferon regulatory factor 3 (IRF3) has been implicated in adipogenesis. However, the role of IRF3 in obesity and obesity-associated disorders remains unclear. Here, we show that IRF3 expression in human adipose tissues is positively associated with insulin sensitivity and negatively associated with type 2 diabetes. In mouse pre-adipocytes, deficiency of IRF3 results in increased expression of PPARγ and PPARγ-mediated adipogenic genes, leading to increased adipogenesis and altered adipocyte functionality. The IRF3 knockout (KO) mice develop obesity, insulin resistance, glucose intolerance, and eventually type 2 diabetes with aging, which is associated with the development of white adipose tissue (WAT) inflammation. Increased macrophage accumulation with M1 phenotype which is due to the loss of IFNβ-mediated IL-10 expression is observed in WAT of the KO mice compared to that in wild-type mice. Bone-marrow reconstitution experiments demonstrate that the nonhematopoietic cells are the primary contributors to the development of obesity and both hematopoietic and nonhematopoietic cells contribute to the development of obesity-related complications in IRF3 KO mice. This study demonstrates that IRF3 regulates the biology of multiple cell types including adipocytes and macrophages to prevent the development of obesity and obesity-related complications and hence, could be a potential target for therapeutic interventions for the prevention and treatment of obesity-associated metabolic disorders.
Identifiants
pubmed: 34091599
doi: 10.1038/s41418-021-00798-9
pii: 10.1038/s41418-021-00798-9
pmc: PMC8563729
doi:
Substances chimiques
Interferon Regulatory Factor-3
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3022-3035Subventions
Organisme : Medical Research Council
ID : MC_UU_00014/2
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/12/13/29853
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/18/7/33636
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12012/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0802051
Pays : United Kingdom
Organisme : Medical Research Council
ID : MRC_MC_UU_12012/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400192
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_G0802535
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12012/5
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MRC_MC_UU_12012/2
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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