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

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dc.contributor.authorTang, Peng
dc.contributor.authorVirtue, Sam
dc.contributor.authorGoie, Jian Yi Gerald
dc.contributor.authorPng, Chin Wen
dc.contributor.authorGuo, Jing
dc.contributor.authorLi, Ying
dc.contributor.authorJiao, Huipeng
dc.contributor.authorChua, Yen Leong
dc.contributor.authorCampbell, Mark
dc.contributor.authorMoreno-Navarrete, José Maria
dc.contributor.authorShabbir, Asim
dc.contributor.authorFernández-Real, José-Manuel
dc.contributor.authorGasser, Stephan
dc.contributor.authorKemeny, David Michael
dc.contributor.authorYang, Henry
dc.contributor.authorVidal-Puig, Antonio
dc.contributor.authorZhang, Yongliang
dc.date.accessioned2021-11-02T16:32:54Z
dc.date.available2021-11-02T16:32:54Z
dc.date.issued2021-06-05
dc.date.submitted2020-10-15
dc.date.updated2021-11-02T16:32:53Z
dc.description.abstractAbstract: 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.
dc.identifier.doi10.17863/CAM.77628
dc.identifier.eissn1476-5403
dc.identifier.issn1350-9047
dc.identifier.others41418-021-00798-9
dc.identifier.other798
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330187
dc.languageen
dc.publisherNature Publishing Group UK
dc.subjectArticle
dc.subject/631/250/127/1212
dc.subject/692/308/2778
dc.subject/13
dc.subject/13/21
dc.subject/13/51
dc.subject/13/95
dc.subject/13/106
dc.subjectarticle
dc.titleRegulation of adipogenic differentiation and adipose tissue inflammation by interferon regulatory factor 3
dc.typeArticle
dcterms.dateAccepted2021-04-26
prism.endingPage3035
prism.issueIdentifier11
prism.publicationNameCell Death & Differentiation
prism.startingPage3022
prism.volume28
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41418-021-00798-9
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