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Publication
IRF3 promotes adipose inflammation and insulin resistance and represses
browning.
Authors Kumari M, Wang X, Lantier L, Lyubetskaya A, Eguchi J, Kang S, Tenen D, Roh HC,
Kong X, Kazak L, Ahmad R, Rosen ED
Submitted By Submitted Externally on 10/26/2016
Status Published
Journal The Journal of clinical investigation
Year 2016
Date Published
Volume : Pages 126 : 2839 - 54
PubMed Reference 27400129
Abstract The chronic inflammatory state that accompanies obesity is a major contributor
to insulin resistance and other dysfunctional adaptations in adipose tissue.
Cellular and secreted factors promote the inflammatory milieu of obesity, but
the transcriptional pathways that drive these processes are not well described.
Although the canonical inflammatory transcription factor NF-?B is considered to
be the major driver of adipocyte inflammation, members of the interferon
regulatory factor (IRF) family may also play a role in this process. Here, we
determined that IRF3 expression is upregulated in the adipocytes of obese mice
and humans. Signaling through TLR3 and TLR4, which lie upstream of IRF3, induced
insulin resistance in murine adipocytes, while IRF3 knockdown prevented insulin
resistance. Furthermore, improved insulin sensitivity in IRF3-deficient mice was
associated with reductions in intra-adipose and systemic inflammation in the
high fat-fed state, enhanced browning of subcutaneous fat, and increased adipose
expression of GLUT4. Taken together, the data indicate that IRF3 is a major
transcriptional regulator of adipose inflammation and is involved in maintaining
systemic glucose and energy homeostasis.




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