124 Wnt signaling activation causes ATGL-dependent lipolysis in skin fibrosis

Fibrosis is the pathological accumulation of extracellular matrix and can occur in all soft tissues. In many organs, including skin, fibrosis also associated with a loss fat or lipid-filled cells. dermal adipose tissue has critical roles which are likely impacted by fibrotic remodeling. Despite identifying numerous dysregulated signaling pathways common to disease, mechanism remains poorly understood. Wnt widely across diseases known impact adipocyte cell fate commitment, but causal role lipid breakdown mature adipocytes hasn’t yet been demonstrated. We found activation vitro vivo results depletion. Lipolysis process stored sequence lipases beginning triglyceride lipase (ATGL). hypothesized that dermis stimulates excessive ATGL-dependent lipolysis adipocytes. Using an inducible murine model dermis, we first demonstrate ATGL/lipolysis axis visible droplets electron microscopy. Second, show Wnt-induced depletion dependent on ATGL vivo. Third, genetic ablation Atgl confers protection against early collagen remodeling skin fibrosis, suggesting implications for ECM accumulation. Our involvement remodeling, highlighting new target therapies potential both phenotypes.