Unknown

Dataset Information

0

IRF3 promotes adipose inflammation and insulin resistance and represses browning.


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.

SUBMITTER: Kumari M 

PROVIDER: S-EPMC4966307 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

IRF3 promotes adipose inflammation and insulin resistance and represses browning.

Kumari Manju M   Wang Xun X   Lantier Louise L   Lyubetskaya Anna A   Eguchi Jun J   Kang Sona S   Tenen Danielle D   Roh Hyun Cheol HC   Kong Xingxing X   Kazak Lawrence L   Ahmad Rasheed R   Rosen Evan D ED  

The Journal of clinical investigation 20160711 8


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-κB is considered to be the major driver of adipocyte inflammation, members of the interferon regulatory factor (IRF) family ma  ...[more]

Similar Datasets

| S-EPMC4320010 | biostudies-literature
| S-EPMC6021131 | biostudies-literature
| S-EPMC3088110 | biostudies-literature
| S-EPMC5873875 | biostudies-other
| S-EPMC5985036 | biostudies-literature
| S-EPMC5314706 | biostudies-literature
| S-EPMC9611559 | biostudies-literature
2024-02-09 | GSE213048 | GEO
2024-03-14 | PXD047864 | Pride
| S-EPMC7409818 | biostudies-literature