cGAS-STING signaling and function in metabolism and kidney diseases

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway senses the presence of cytosolic DNA and, in turn, triggers downstream signaling to induce the expression of inflammatory and type I interferon genes in immune cells. Whereas the innate immune function of the cGAS-STING pathway is well studied over the past years, emerging evidence suggests that this signaling pathway may have additional functions beyond innate immune surveillance. Consistent with this notion, dysregulation of the cGAS-STING signaling pathway in adipocytes, hepatocytes, and renal proximal tubule epithelial cells are associated with metabolic dysfunction, impaired energy homeostasis, and kidney diseases. In this review, we summarize current understanding of the cGAS-STING pathway in several metabolic diseases such as obesity, insulin resistance, alcoholic and nonalcoholic fatty liver diseases, as well as acute kidney injury and chronic kidney disease. We also review the interaction between the cGAS-STING pathway and lipid metabolism. Lastly, we discuss potential mechanisms by which cGAS-STING signaling regulates metabolism and point toward future avenues of research targeting the cGAS-STING pathway as possible means to treat common metabolic disorders.

Automated summary

The cGAS-STING signaling pathway plays a role not only in innate immunity but is also associated with metabolic diseases such as obesity, fatty liver, and kidney diseases. It may affect energy homeostasis by regulating lipid metabolism, providing new research avenues for targeted treatment of metabolic disorders.