Regulation of fatty acid uptake into tissues: lipoprotein lipase- and CD36-mediated pathways

Abstract

Cells obtain FAs either from LPL-catalyzed hydrolysis of lipoprotein triglyceride or from unesterified FFAs associated with albumin. LPL also influences uptake of esterified lipids such as cholesteryl and retinyl esters that are not hydrolyzed in the plasma. This process might not involve LPL enzymatic activity. LPL is regulated by feeding/fasting, insulin, and exercise. Although a number of molecules may affect cellular uptake of FFAs, the best characterized is CD36. Genetic deletion of this multiligand receptor reduces FFA uptake into skeletal muscle, heart, and adipose tissue, and impairs intestinal chylomicron production and clearance of lipoproteins from the blood. CD36 is regulated by some of the same factors that regulate LPL, including insulin, muscle contraction, and fasting, in part, via ubiquitination. LPL and CD36 actions in various tissues coordinate biodistribution of fat-derived calories.

Fig. 1.

LPL-mediated uptake of lipids. Left panel: LPL hydrolyzes lipoprotein TG releasing FFAs that are internalized by cells. Much of this uptake is via cell surface receptors such as CD36. Middle panel: LPL also creates remnant lipoproteins that interact with cell surface lipoprotein receptors. Right panel: Another option for uptake of core lipids is that lipolysis creates small particles that contain both surface and core lipid as well as apoproteins, exclusive of apoB. Inactive LPL (iLPL) on the cell surface might facilitate cellular internalization of these particles. Such a pathway might allow cholesteryl and retinyl ester uptake into “high lipolysis” organs such as the heart.