Regulation of adipogenic differentiation and adipose tissue inflammation by interferon regulatory factor 3
| Autor: | Antonio Vidal-Puig, Huipeng Jiao, Henry Yang, Chin Wen Png, Stephan Gasser, Ying Li, Yongliang Zhang, Mark Campbell, Asim Shabbir, David M. Kemeny, Jing Guo, José Manuel Fernández-Real, Sam Virtue, José María Moreno-Navarrete, Jian Yi Gerald Goie, Peng Tang, Yen Leong Chua |
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| Přispěvatelé: | Apollo - University of Cambridge Repository |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Adipose tissue Inflammation 13/106 White adipose tissue 631/250/127/1212 13 Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Insulin resistance 13/21 Internal medicine Adipocyte medicine Animals Humans Obesity Metabolisme -- Trastorns Metabolism -- Disorders Molecular Biology 692/308/2778 business.industry article Adipose tissues Cell Differentiation Cell Biology medicine.disease Teixit adipós 030104 developmental biology Endocrinology Adipose Tissue chemistry Preclinical research Adipogenesis 13/51 13/95 Obesitat Interferon Regulatory Factor-3 Interferons medicine.symptom IRF3 business 030215 immunology Interferon regulatory factors |
| Zdroj: | Cell Death and Differentiation Cell Death and Differentiation, 2021, vol. 28, p. 3022-3035 Articles publicats (D-CM) DUGiDocs – Universitat de Girona instname |
| Popis: | 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 This study was supported by grants from the National Medical Research Council (OFIRG/0059/2017) of Singapore (to YZ), A*STAR-NHMRC (bilateral grant NHMRC2017-SG006 to YZ), the National Research Foundation, Prime Minister’s Office, Singapore under its Campus of Research Excellence and Technological Enter- prise (CREATE) Programme (to YZ), the NUS Global Asia Institute (R571-000-043-133 to YZ), British Heart Foundation (Programme Grant RG/18/7/33636 to AVP), Medical Research Council (MRC_MC_UU_12012/2 to AVP, and Medical Research Council Disease Model Core facilities of the Wellcome Trust-MRC MDU (MRC_MC_UU_12012/5 to AVP), SGR 2017/00734 (to JF) and PI18/01022 (to JF) |
| Databáze: | OpenAIRE |
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