Abnormalities of fatty acid (FA) metabolism contribute to etiology of inflammation and diabetes. The Abumrad group identified the membrane protein CD36 as a facilitator of high affinity cellular FA uptake and as a signaling protein important in metabolic regulation. CD36-mediated signaling influences muscle FA oxidation, gut chylomicron production and secretion of regulatory peptides, hepatic VLDL output, etc. CD36 signals to raise cellular Ca2+ via store operated Ca2+ flux which regulates generation of FA-derived eicosanoids and mediates orosensory fatty perception by taste bud cells.
CD36 is a metabolic regulator. It is required for cellular switching of fuel preference between glucose and FA by its simultaneous regulation of the metabolism of FA and glucose. FA-sensitive CD36 signaling alters protein interactions in the AMPK and insulin receptor pathways. Another interesting aspect of metabolic regulation by CD36 is that it transduces markedly different metabolic signals in response to saturated versus unsaturated FA ligands.
CD36 function and dysfunction are relevant to humans. We found that CD36 gene variants influence endothelial function, metabolic syndrome risk, and levels of fasting and postprandial plasma lipids. Genetically determined low CD36 expression in muscle is associated with incidence of type2 diabetes.
Dr. Abumrad serves as associate director of the Nutrition and Obesity Research Center (NORC) at Washington University and as director of the NORC Adipocyte Biology and Molecular Nutrition (ABMN) Core. The ABMN Core and the Abumrad lab assist young investigators transitioning to independence and help facilitate research in molecular nutrition.