cGAS: bridging immunity and metabolic regulation

Recent advances have revealed that cyclic guanosine monophosphate-adenosine monophosphate (AMP) synthase (cGAS), classically recognized as a cytosolic DNA sensor, plays crucial roles beyond innate immunity. Particularly in the adipose tissue, cGAS functions as a metabolic sentinel, responding to mitochondrial stress and contributing to inflammation, insulin resistance, and energy imbalance. These effects occur through both stimulator of interferon genes (STING)-dependent and STING-independent pathways, involving autophagy, chromatin remodeling, and transcriptional reprogramming. Here, we propose a paradigm shift positioning cGAS at the intersection of immunity and metabolism. We explore its multifaceted roles in adipocytes and other metabolic tissues, highlighting emerging therapeutic opportunities and future research directions.