IRF3 is a Critical Regulator of Adipose Glucose and Energy Homeostasis

Xun Wang

Obesity is associated with a state of chronic inflammation, which is believed to contribute to insulin resistance. We previously identified interferon regulatory factor 3 (IRF3) as an anti-adipogenic transcription factor with high expression in adipocytes. Because IRF3 is known to drive expression of pro-inflammatory genes in immune cells, we hypothesized that it may also promote inflammation and insulin resistance in adipocytes. Consistent with our expectations, we found that the expression of inflammatory genes in adipocytes was induced by IRF3 overexpression, while knockdown of IRF3 had the opposite effect. Despite this effect on local adipocyte gene expression, we found that Irf3-/- mice did not show evidence of altered systemic inflammation. Nonetheless, Irf3-/- mice did display altered metabolism relative to their wild type (WT) littermates. For example, high fat diet (HFD) fed...