Interferon regulatory factor 3 beyond innate immunity: Regulation in obesity and metabolic disorders

Interferon regulatory factor 3 (IRF3) is a transcription factor known primarily for its role in antiviral immunity via regulation of type I interferons (IFNs). Recent research has broadened its significance to encompass metabolic disorders, particularly obesity and diabetes. Obesity is characterized by chronic low-grade inflammation, insulin resistance, and metabolic dysfunction, all of which are increasingly found to be associated with immune signaling pathways. IRF3 has emerged as an important regulator in the development of obesity and type 2 diabetes (T2D), predominantly through its regulation of inflammatory cytokines production in various cells in adipose tissue. In obese individuals, IRF3 is activated in the adipocytes and adipose tissue macrophages, to promote the expression of inflammatory cytokines, thereby contributing to chronic inflammation and exacerbating insulin resistance. Moreover, IRF3 has been linked to mitochondrial dysfunction in hepatic disorders, further amplifying metabolic stress and imbalances associated with obesity. The growing evidence suggests that IRF3 is an important mediator in both immune and metabolic pathways, highlighting its potential as a target for the development of therapeutic interventions for obesity-related inflammation and metabolic dysfunction.