cGAS Inhibits ALDH2 to Suppress Lipid Droplet Function and Regulate MASLD Progression

mice fed with a modified high-fat diet develop exacerbated metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by excessive lipid droplet accumulation in livers compared to wild-type controls. In human MASLD patient cohorts, increased cGAS but reduced ALDH2 mRNA expression is observed relative to healthy individuals. Together, this findings uncover a previously unrecognized role of cGAS in metabolic regulation, independent of its innate immune function. By suppressing ALDH2, cGAS controls lipid droplet biogenesis and stress responses, with direct implications for MASLD pathogenesis.