ADPN

Adiponectin, an adipocyte-derived secretory factor, enhances insulin sensitivity, reduces inflammation, and promotes cell survival, yet the underlying mechanism remains unclear. This study identifies a critical role of adiponectin in stimulating ceramidase activity through its receptors, AdipoR1 and AdipoR2, leading to increased ceramide catabolism and the production of the anti-apoptotic metabolite sphingosine-1-phosphate (S1P), independent of AMP-activated protein kinase (AMPK). Using apoptosis models in pancreatic beta cells and cardiomyocytes, the findings show that adiponectin overexpression reduces caspase-8-mediated apoptosis, while adiponectin deficiency exacerbates cell death via sphingolipid-mediated mechanisms. Cells lacking both adiponectin receptors exhibit impaired ceramidase activity, elevated ceramide levels, and increased susceptibility to palmitate-induced apoptosis. These findings suggest that adiponectin’s systemic benefits are mediated through sphingolipid metabolism, providing a unifying mechanism for its protective effects in metabolic and cardiovascular health.