Lipoprotein Lipase

Lipoprotein lipase (LPL) is the enzyme responsible for the hydrolysis (breakdown) of triacylglycerols (TAG, or dietary fat) from lipoprotein carrying molecules into nonesterified free fatty acids and 2-monoacyglycerol for incorporation into tissues such as adipose, heart, and skeletal muscle. LPL plays an important role in lipid metabolism and [Page 429]dysregulation of this enzyme has been implicated in pathologies associated with obesity, including cardiovascular disease.

Within adipose tissue, skeletal muscle, and heart, LPL is located on the capillary endothelium and is attached to the cell surface by heparin sulfate proteoglycan chains. LPL catalyzes the rate-limiting step in the breakdown of TAG from lipoproteins (proteins which transport lipids around the body) so that free fatty acids can be taken up by other target tissues. Two examples of lipoproteins that transport TAGs are chylomicrons and very low density lipoproteins (VLDLs). Dietary TAG are incorporated into chylomicrons and secreted by the intestine, while endogenous TAG is incorporated into VLDL and secreted by the liver. Upon secretion, the lipoproteins migrate to the skeletal muscle, adipose tissue, or the heart.

Apolipoprotein C2, which is present on the lipoprotein particles, serves as a cofactor for the TAG hydrolysis action of LPL. This reaction is necessary for cellular utilization of TAG as the lipoprotein molecules are normally too large to cross the capillary endothelium. Once inside the cell, the fatty acids and monoacylglycerol chains are either re-esterified (put back together) as TAGs for storage, or they are broken down further for energy needs.

Dysregulation of LPL in humans is associated with increased risk for coronary heart disease. Reduced activity of LPL is associated with hypertriglyceridemia, which is a risk factor for heart disease. Conversely, enhanced activity of LPL results in the increased release of remnant lipoproteins in circulation, which are subject for uptake by inflammatory macrophages, which may increase risk for atherosclerosis. In addition, LPL is expressed in macrophages from atherosclerotic lesions. Macrophage LPL activity is proposed to be proatherogenic, promoting uptake of lipids into the macrophages, which become incorporated into atherosclerotic lesions and subsequently increase the size of these lesions.