Repository logo
 

Regulation of adipogenic differentiation and adipose tissue inflammation by interferon regulatory factor 3.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Tang, Peng 
Virtue, Sam 
Goie, Jian Yi Gerald 
Png, Chin Wen 
Guo, Jing 

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.

Description

Keywords

Adipose Tissue, Animals, Cell Differentiation, Humans, Inflammation, Interferon Regulatory Factor-3, Male, Mice, Obesity

Journal Title

Cell Death Differ

Conference Name

Journal ISSN

1350-9047
1476-5403

Volume Title

Publisher

Springer Science and Business Media LLC
Sponsorship
British Heart Foundation (RG/18/7/33636)
MRC (Unknown)
Medical Research Council (MC_UU_12012/2)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (G0802051)
Medical Research Council (MC_G0802535)
Medical Research Council (G0400192)
British Heart Foundation (None)
MRC (MC_UU_00014/2)
Medical Research Council (MC_PC_12012)