Hepatic Lipase, High Density Lipoproteins, and Hypertriglyceridemia

Abstract

Hepatic lipase (HL) is a lipolytic enzyme that contributes to the regulation of plasma triglyceride (TG) levels. Elevated TG levels may increase the risk of developing coronary heart disease, and studies suggest that mutations in the HL gene may be associated with elevated TG levels and increased risk of coronary heart disease. Hepatic lipase facilitates the clearance of TG from the very low density lipoprotein (VLDL) pool, and this function is governed by the composition and quality of high density lipoprotein (HDL) particles. In humans, HL is a liver resident enzyme regulated by factors that release it from the liver and activate it in the bloodstream. HDL regulates the release of HL from the liver and HDL structure controls HL transport and activation in the circulation. Alterations in HDL-apolipoprotein composition can perturb HL function by inhibiting the release and activation of the enzyme. HDL structure may therefore affect plasma TG levels and coronary heart disease risk. Triglycerides and Heart DiseaseElevated plasma triglyceride (TG) levels have been viewed as a risk factor for coronary heart disease (CHD) for more than a decade.1,2 Plasma TG levels are regulated by both synthesis and degradation of both very low density lipoprotein (VLDL) and chylomicron particles. The clearance of TG-rich lipoproteins from the circulation is controlled by the actions of lipoprotein lipase (LPL) and hepatic lipase (HL) and by the interlipoprotein exchange of TG by cholesteryl ester transfer protein. Lipoprotein lipase is the predominant TG lipase and is responsible for hydrolyzing TG in chylomicrons and VLDL, whereas HL is both a phospholipase and a TG lipase and plays an important role in HDL metabolism and in the conversion of VLDL to LDL.3 Single nucleotide polymorphisms (SNPs) in the HL gene (LIPC) have been shown to associate with plasma lipid concentrations and increased CHD risk. 4,5 Hepatic lipase deficiency is a result of relatively rare LIPC mutations that give rise to a loss in circulating HL activity (due to impaired secretion or inactive enzyme) and cause an increase in TG-rich HDL and VLDL remnants and increased CHD risk.

Binding of human apoA-I[K107del] variant to TG-rich particles: implications for mechanisms underlying hypertriglyceridemia

“…Further studies may unravel additional mechanisms contributing to the development of HTG associated with apoA-I mutations. It is possible, for example, that apoA-I mutations associated with HTG may impair the ability of apoA-I to liberate hepatic lipase from heparan sulfate proteoglycans ( 37,52 ) and thus lead to a reduced amount of the active enzyme and contribute to HTG. Our study shows that enhanced binding of apoA-I to TG-rich lipoproteins may be one of the factors contributing to the development of HTG associated with human apoA-I mutation.…”

LIPC rs10468017, rs493258 and LPL rs12678919 Role in Patients With Age- Related Macular Degeneration

“…Genotype-phenotype associations are known to vary from country to country (11)(12)(13)(14)(15)(16)(17)(18)(19), so the aim of our study was to determine the genotype frequency of LIPC rs10468017, rs493258 and LPL rs126789919 in patients with early and exudative AMD in Lithuanian subjects.…”

“…Liver cells express LIPC and excrete the enzyme into blood [13]. In the blood, the LIPC enzyme converts very low density lipoproteins (VLDL) and medium-density lipoproteins (MDL) to low density lipoproteins (LDL).…”

“…Disruption of the LIPC function increases the risk of suffering from these diseases because the lack of the enzyme means that VLDL and MDL are not converted into LDL and HDL. As a result, cholesterol and triglycerides are not removed from the circulation [13].…”

“…Disruption of the LIPC function increases the risk of suffering from these diseases because the lack of the enzyme means that VLDL and MDL are not converted into LDL and HDL. As a result, cholesterol and triglycerides are not removed from the circulation [13].LPL gene encodes lipoprotein and is localized on the short arm of chromosome 8, position 22 (8p22). This enzyme is found on the surface of capillary cells which play a key role in the digestion and However, results of studies related to AMD in different cohorts on the reported HDL cholesterol metabolism genes, including the hepatic lipase (LIPC) and lipoprotein lipase (LPL) genes are inconsistent [12,[16][17][18][19].…”