The relevance of adiponectin to insulin sensitivity has been elucidated over the last two decades. As a promoter of ceramide degradation, it works through its cognate receptors, AdipoR1 and AdipoR2, to alter bioactive sphingolipid species. Adiponectin diminishes the accumulation of ceramide, a lipid metabolite which can play a causal role in obesity-induced insulin resistance. Concurrently, adiponectin stimulates the production of sphingosine-1-phosphate (S1P), a cyto-protective molecule that accentuates adiponectin's positive metabolic effects. This review focuses on recent work that solidifies knowledge of the adiponectin signaling pathway, gives new insight into some notable characteristics of adiponectin's receptors, and most importantly, affirms adiponectin receptor agonism as a viable therapeutic tool to combat elevated ceramide levels and improve insulin sensitivity in obese patients with type II diabetes.
Keywords: AMPK; Ceramide; S1P; ceramidase; insulin resistance.