The Differential Effects of HDL Subpopulations on Lipoprotein Lipase (LPL)-Mediated VLDL Catabolism

Abstract

High-density lipoprotein (HDL) subpopulations functional assessment is more relevant for HDL anti-atherogenic activity than cholesterol level. The aim of the study was to assess the impact of HDL-2 and HDL-3 on lipoprotein lipase (LPL)-mediated very-low-density lipoprotein (VLDL) catabolism related to hypertriglyceridemia development. VLDL and HDLs were isolated from serum by ultracentrifugation. VLDL was incubated with LPL in the absence and presence of total HDL or HDL subpopulations. Next, VLDL remnants were separated, and their composition and electrophoretic mobility was assessed. Both HDL subpopulations increased the efficiency of triglyceride lipolysis and apolipoprotein CII and CIII removal from VLDL up to ~90%. HDL-3 exerted significantly greater impact than HDL-2 on apolipoprotein E (43% vs. 18%, p < 0.001), free cholesterol (26% vs. 18%, p < 0.05) and phospholipids (53% vs. 43%, p < 0.05) removal from VLDL and VLDL remnant electrophoretic mobility (0.18 vs. 0.20, p < 0.01). A greater release of these components was also observed in the presence of total HDL with a low HDL-2/HDL-3 cholesterol ratio. Both HDL subpopulations affect VLDL composition during lipolysis, but HDL-3 exhibited a greater effect on this process. Altered composition of HDL related to significant changes in the distribution between HDL-2 and HDL-3 can influence the VLDL remnant features, affecting atherosclerosis progression.

High-Density Lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner

“…6 , to identify further biochemical parameters that make LTHC HDL different from LTLC and LTLC HDL. HDL can be divided into different subpopulations or subfractions for which each HDL particle varies in protein and lipid content, size, and density [48] . HDL3 are the smallest protein-enriched particles that are subsequently converted into the large HDL2, which have other subdivisions like HDL2b and HDL2a [49] .…”

Spotlight on very-low-density lipoprotein as a driver of cardiometabolic disorders: Implications for disease progression and mechanistic insights

“…The reverse-remnant cholesterol transport mechanism, which is the acquisition of VLDL surface components by HDL during LPL-mediated lipolysis, plays an important role in VLDL catabolism ( 57 ). HDL affects the lipolysis of VLDL TGs and the release of surface lipids, free cholesterol, phospholipids, and exchangeable apoE, apoCII, and apoCIII from VLDL during lipolysis ( 58 ). HDL can also be classified into subpopulations according to size, apolipoprotein content, charge, mass, and density.…”

“…Although subpopulations of both large and small HDL particles increased VLDL TG lipolysis efficiency and surface material removal from VLDL, the small, protein-enriched HDL particles exhibited a greater effect on this process and promoted a more efficient release of surface components, thereby affecting the properties of the generated remnants. Loss of apoC proteins from VLDL during lipolysis promoted the metabolism of apoB-containing lipoprotein because both apoCII and apoCIII inhibit the binding of apoB lipoproteins to the LDLR ( 58 ).…”

Afamin Levels and Their Correlation with Oxidative and Lipid Parameters in Non-diabetic, Obese Patients

“…There is an inverse relationship between Tg elevation and high-density lipoprotein (HDL) cholesterol levels [ 15 ]. The reason for this is the altered maturation of HDL particles in the presence of lipid components released during the breakdown of Tg [ 16 ]. The Tg content of HDL increases and the metabolism of these particles by hepatic lipase accelerates [ 13 , 16 ].…”

“…The reason for this is the altered maturation of HDL particles in the presence of lipid components released during the breakdown of Tg [ 16 ]. The Tg content of HDL increases and the metabolism of these particles by hepatic lipase accelerates [ 13 , 16 ]. There is also a change in the composition of LDL: the level of small, dense LDL particles—prone to oxidation—increases, resulting in elevated oxidized LDL (oxLDL) concentrations and accelerated atherogenesis [ 17 ].…”