Our research identified the membrane protein CD36 as a high affinity receptor for long chain fatty acid (FA) and as a signaling protein that plays a key role in metabolic regulation. We recently documented that CD36-mediated signal transduction involves modulation of the assembly/disassembly of proteins in the AMPK and insulin signaling pathways and we are exploring how this affects activity of downstream proteins of FA and glucose metabolism. In humans, we found that variants in the CD36 gene influence blood lipids and risk of metabolic syndrome and more recently endothelial function. We will be exploring the contribution of CD36 polymorphisms to the susceptibility for endothelial dysfunction, a condition that often precedes insulin resistance, inflammation and onset of metabolic pathologies.