Regulation of adipogenic differentiation and adipose tissue inflammation by interferon regulatory factor 3
Authors
Tang, Peng
Virtue, Sam
Goie, Jian Yi Gerald
Png, Chin Wen
Guo, Jing
Li, Ying
Jiao, Huipeng
Chua, Yen Leong
Campbell, Mark
Moreno-Navarrete, José Maria
Shabbir, Asim
Fernández-Real, José-Manuel
Gasser, Stephan
Kemeny, David Michael
Yang, Henry
Vidal-Puig, Antonio
Zhang, Yongliang
Publication Date
2021-06-05Journal Title
Cell Death & Differentiation
ISSN
1350-9047
Publisher
Nature Publishing Group UK
Volume
28
Issue
11
Pages
3022-3035
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Tang, P., Virtue, S., Goie, J. Y. G., Png, C. W., Guo, J., Li, Y., Jiao, H., et al. (2021). Regulation of adipogenic differentiation and adipose tissue inflammation by interferon regulatory factor 3. Cell Death & Differentiation, 28 (11), 3022-3035. https://doi.org/10.1038/s41418-021-00798-9
Abstract
Abstract: 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.
Keywords
Article, /631/250/127/1212, /692/308/2778, /13, /13/21, /13/51, /13/95, /13/106, article
Identifiers
s41418-021-00798-9, 798
External DOI: https://doi.org/10.1038/s41418-021-00798-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330187
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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