Deficiency results in a rare disorder of lipid metabolism causing the chylomicronemia syndrome.
Deficiency of this enzyme causes severe hypertriglyceridemia by blocking the clearance of triglyceride rich lipoproteins fro the plasma.
Lipoprotein lipase is a critical enzyme in TG metabolism and a target for TG lowering therapies such as fibrates.
Genetic mutations that decrease lipoprotein lipase activity and increase TG levels are associated with increased coronary heart disease risk.
Lipoprotein lipase (LPL) is a member of the lipase gene family, which includes pancreatic lipase, hepatic lipase, and endothelial lipase.
A water-soluble enzyme that hydrolyzes triglycerides in lipoproteins, such as those found in chylomicrons and very low-density lipoproteins (VLDL), into two free fatty acids and one monoacylglycerol molecule.
It promotes the cellular uptake of chylomicron remnants, cholesterol-rich lipoproteins, and free fatty acids.
LPL requires ApoC-II as a cofactor.
LPL is located on Chromosome 8 Band 8p21.3 LPL is attached to the surface of endothelial cells in capillaries by the protein glycosylphosphatidylinositol HDL-binding protein 1 (GPIHBP1) and by heparan sulfated proteoglycans.
LPL is most widely distributed in adipose, heart, and skeletal muscle tissue, as well as in lactating mammary glands.
LPL is secreted from parenchymal cells as a glycosylated homodimer, after which it is translocated through the extracellular matrix and across endothelial cells to the capillary lumen.
After translation, the newly synthesized protein is glycosylated in the endoplasmic reticulum.
Glucosidases then remove terminal glucose residues responsible for the conformational change needed for LPL to form homodimers and become catalytically active.
In the Golgi apparatus, the oligosaccharides are further altered to result in either two complex chains, or two complex and one high-mannose chain.
It is composed of two distinct regions: the larger N-terminus domain that contains the lipolytic active site, and the smaller C-terminus domain.
Triglyceride binds to the C-terminal domain and the lid region, inducing a conformation change in LPL to make the active site accessible.
The C-terminal domain appears to confer LPL’s substrate specificity; it has a higher affinity for large triacylglyceride-rich lipoproteins than cholesterol-rich lipoproteins.
The C-terminal domain is also important for binding to LDL’s receptors.
LPL therefore serves as a bridge between the cell surface and lipoproteins.
LPL binding to the cell surface or receptors is not dependent on its catalytic activity.
LPL, which is expressed on endothelial cells in the heart, muscle, and adipose tissue.
LPL has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake.
Through catalysis, VLDL is converted to IDL and then to LDL.
Mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism.
The circadian clock may have a role in the control of Lpl mRNA levels in peripheral tissues.
Insulin is known to activate LPL in adipocytes and its placement in the capillary endothelium.
In contrast, insulin has been shown to decrease expression of muscle LPL.
Muscle and myocardial LPL is activated by glucagon and adrenaline.
During fasting, LPL activity increases in muscle tissue and decreases in adipose tissue, whereas after a meal, the opposite occurs.
After days on a high-carbohydrate or a high-fat diet, LPL activity increased significantly in LPL activity in muscle and adipose tissues 6 hours after a meal of either composition, but there was a significantly greater rise in adipose tissue LPL in response to the high-carbohydrate diet compared to the high-fat diet.
There was no difference between the two diets’ effects on insulin sensitivity or fasting LPL activity in either tissue.
The concentration of LPL on endothelial cell surface cannot be regulated by endothelial cells, as they neither synthesize nor degrade LPL.
LPL concentration on endothelial cells occurs by managing the flux of LPL arriving at the lipolytic site and by regulating the activity of LPL present on the endothelium.
ANGPTL4 is a key protein involved in controlling the activity of LPL and serves as a local inhibitor of LPL.
Induction of ANGPTL4 accounts for the inhibition of LPL activity in white adipose tissue during fasting, and is a physiological regulator of LPL activity in a variety of tissues.
Feeding induces ANGPTL8, activating the ANGPTL8–ANGPTL3 pathway, which inhibits LPL in cardiac and skeletal muscles, thereby making circulating triglycerides available for uptake by white adipose tissue, in which LPL activity is elevated owing to diminished ANGPTL4
The reverse is true during fasting, which suppresses ANGPTL8 but induces ANGPTL4, thereby directing triglycerides to muscles.
Lipoprotein lipase deficiency leads to hypertriglyceridemia.
A high adipose tissue LPL response to a high-carbohydrate diet may predispose toward fat gain.
A high-carbohydrate diet increases in adipose tissue LPL activity per adipocyte, or a decrease in skeletal muscle LPL activity per gram of tissue.