Role of IRF3 as a key regulator of immunometabolism in macrophages and adipocytes

Obesity induces a state of chronic low-grade inflammation, marked by immune regulatory cell infiltration of fat, liver and muscle and production of proinflammatory cytokines/chemokines to result in defects regarding insulin signaling and metabolic function as observed in type-2 diabetes. As opposed to well-understood TLR4-MyD88-IKKβ-NF-κB transcriptional pathway, little is known about the MyD88-independent arm (i.e. TLR4-TBK1-IKKε axis) of TLR4 signaling pathway. It remains to be seen how the major downstream transcriptional effector of this pathway, called interferon regulatory factor (IRF)-3, gets activated by overnutrition and functions in adipose tissue and macrophages to regulate insulin sensitivity and inflammatory responses. Public Health Relevance: Our findings will highlight an unappreciated role of IRF3 as a driver of metabolic dysfunction and discover a new potential therapeutic target that would improve the resolution of inflammation in obese individuals with diabetes and associated complications.