Through the cytosolic DNA sensor cGAS, mtDNA activates the STING-interferon regulatory Factor 3 pathway and induces a chronic sterile inflammatory response in mouse adipose tissue.313,314 In STING-deficient mice, the effects of diet-induced obesity, including endothelial inflammation (in adipose tissue), insulin resistance, and glucose intolerance, were alleviated.314 These findings support the notion that STING signaling plays a critical role in obesity-related adipose inflammation and insulin resistance. The gene discussed is IRF3; the disease is obesity due to melanocortin 4 receptor deficiency.