Adiponectin and related C1q/TNF related proteins bind selectively to anionic phospholipids and sphingolipids
Adiponectin (also known as Acrp30) is a well known adipokine associated with protection from cardiovascular disease, insulin resistance, and inflammation. Though multiple studies have investigated the mechanism of action of adiponectin and its relationship with tissue ceramide levels, several aspects of adiponectin biology remain unexplained, including its high circulating levels, tendency to oligomerize, and marked structural similarity to the opsonin C1q. Given the connection between adiponectin and ceramide metabolism, and the lipid binding properties of C1q, we hypothesized that adiponectin may function as a lipid binding protein. Indeed, we found that recombinant adiponectin bound to various anionic phospholipids and sphingolipids, including phosphatidylserine, ceramide 1 phosphate, and sulfatide. The globular head domain of adiponectin was necessary and sufficient for lipid binding. Adiponectin oligomerization was also observed to be critical for efficient lipid binding. In addition to lipids in liposomes, adiponectin bound LDL in an oligomerization dependent manner. Other C1qTNF related protein (CTRP) family members Cbln1, CTRP1, CTRP5, and CTRP13 also bound similar target lipids in liposomes. These findings suggest that adiponectin and other CTRP family members may not only function as classical hormones, but also as lipid binding opsonins or carrier proteins.