Obesity-linked diabetes is a growing public health problem and contributes to cardiovascular disease, the most prevalent cause of death in the U.S. High plasma concentrations fatty acids derived from food intake and excess fat stores and high concentrations of glucose from diet are hallmarks of diabetes. Increasing attention has been directed to fatty acids and their multiple pathophysiological effects.
The plasma membrane receptor CD36 is a key protein that plays central roles in obesity and type 2 diabetes. It binds both fatty acids and oxidized low density lipoprotein (LDL), which has been implicated in promotion of atherosclerosis. However, the mechanistic roles of CD36 are complex and have remained elusive.
In an opensource study published in the Journal of Biological Chemistry, a research group from Boston University applied novel methods to detect binding of fatty acids to CD36 and their effect on internalization of oxidized LDL. Although other research groups have characterized a fatty acid binding site on CD36 and postulated CD36 to be a gatekeeper for fatty acid entry into cells, the lab previously found that CD36 did not increase fatty acid translocation across the plasma membrane.
In the current study all of the common dietary fatty acid types (saturated, unsaturated, trans and polyunsaturated) were shown by a new assay to bind to CD36 at levels greater than expected for a single binding site characterized in previous studies. In cells with CD36 present in the plasma membrane, all of the fatty acids also enhanced oxidized LDL uptake, except for the fish oil fatty acid DHA. This current study adds to the possible mechanisms for fish oil benefits that are now widely recognized.
Since obesity and type 2 diabetes are characterized by high plasma levels of fatty acids, the demonstrated enhancement of oxLDL uptake by increases in common dietary fatty acids may contribute to the pathophysiology of these diseases. The team summise that the new results provided a link between fatty acids, CD36, and atherosclerosis and new drugs can be designed that target the exact mechanism more precisely.