CD36 (SR-B2) as master regulator of cellular fatty acid homeostasis

Transmembrane glycoprotein cluster of differentiation 36 (CD36) is a scavenger receptor class B protein (SR-B2) that serves various functions in lipid metabolism and signaling, in particular facilitating the cellular uptake of long-chain fatty acids. Recent studies have disclosed CD36 to play a prominent regulatory role in cellular fatty acid metabolism in both health and disease.

The rate of cellular fatty acid uptake is short-term (i.e., minutes) regulated by the subcellular recycling of CD36 between endosomes and the plasma membrane. This recycling is governed by the activity of vacuolar-type H+-ATPase (v-ATPase) in the endosomal membrane via assembly and disassembly of two subcomplexes. The latter process is being influenced by metabolic substrates including fatty acids, glucose and specific amino acids, together resulting in a dynamic interplay to modify cellular substrate preference and uptake rates. Moreover, in cases of metabolic disease v-ATPase activity was found to be affected while interventions aimed at normalizing v-ATPase functioning had therapeutic potential.

The emerging central role of CD36 in cellular lipid homeostasis and recently obtained molecular insight in the interplay among metabolic substrates indicate the applicability of CD36 as target for metabolic modulation therapy in disease. Experimental studies already have shown the feasibility of this approach.