The chronic inflammatory state that accompanies obesity is a major contributor to insulin resistance and other metabolic dysfunction features. Despite recent advances in our understanding of the cellular and secreted factors that promote the inflammatory milieu of obesity, we have much less insight into the transcriptional pathways that drive these processes. While most attention has focused on the canonical inflammatory transcription factor NF-KB, other potentially important factors exist, including members of the interferon regultory factor (IRF) family. Here we show that IRF3 expression is upregulated in the adipocytes of obese mice and humans. TLR3/TLR4 activation induces insulin resistance in adipocytes, which can be prevented by IRF3 knockdown. Furthermore, Irf3KO mice display improved insulin sensitivity, associated with reduced intra-adipose and systemic inflammation in the high-fat fed state, enhanced browning of subcutaneous fat, and increased adipose expression of Glut4. Taken together, our data indicates that IRF3 is a major transcriptional regulator of adipose inflammation to maintain systemic glucose and energy homeostasis. SOURCE: Evan Rosen (erosen@bidmc.harvard.edu) - Rosen Lab Beth Israel Deconess Medical Center

Pluto Bioinformatics

GSE81193: Characterising the transcriptional profile of murine 3T3-L1 adipocytes with altered expression of IRF3.