Lipoprotein lipase (LPL) and hepatic lipase (HL) (LPL and HL)

Lipoprotein lipase (LPL) and hepatic lipase (HL, or LIPC) are key enzymes in the metabolism of triglyceride-rich lipoproteins. LPL is primarily expressed in adipose and muscle tissues, where it is anchored to the capillary endothelium and hydrolyzes triglycerides in chylomicrons and very-low-density lipoproteins (VLDL) into free fatty acids (UniProt P06858). Hepatic lipase is synthesized in the liver and functions to further remodel intermediate-density lipoproteins (IDL) and high-density lipoproteins (HDL), facilitating the conversion of IDL to LDL (UniProt P11150). Together, these enzymes ensure the efficient clearance of dietary and endogenous lipids from the bloodstream. Deficiencies or dysregulation of these enzymes lead to severe hypertriglyceridemia, which significantly increases the risk for acute pancreatitis and cardiovascular disease (PubMed: 30124465). Pharmacological intervention often targets these enzymes indirectly; for instance, fibrates activate PPAR-alpha to increase LPL expression (StatPearls: NBK559219). Newer therapeutic agents, such as volanesorsen and evinacumab, work by inhibiting endogenous inhibitors like Apolipoprotein C-III and ANGPTL3, thereby enhancing the activity of these lipases (Nature Reviews Cardiology: 10.1038/s41569-020-0405-2). Heparin is also used in clinical settings to release these enzymes into the plasma for diagnostic measurement of their catalytic activity (StatPearls: NBK537236).

Other names

LPLLIPCHTGLHepatic triacylglycerol lipaseLIPDLipoprotein lipaseHepatic lipase

Activation of lipase activity through PPAR-alpha agonism or by inhibiting endogenous lipase inhibitors such as Apolipoprotein C-III and Angiopoietin-like protein 3 (ANGPTL3).