HDL biology
ApoC-II and apoC-III move from VLDL preferentially into larger HDL3 particles, and a CETP inhibitor does not change this transfer (Biol Chem 2021)
Original title: Apolipoprotein C-II and C-III preferably transfer to both high-density lipoprotein (HDL)2 and the larger HDL3 from very low-density lipoprotein (VLDL)
During triglyceride hydrolysis by lipoprotein lipase, apolipoproteins C-II and C-III are known to move from VLDL to HDL, but the mechanism was unclear. This study incubated isolated HDL2 and HDL3 subfractions with VLDL or biotin-labelled VLDL and quantified the transferred apolipoproteins and lipids by western blot and HPLC. Incubation with VLDL increased net apoC-II and apoC-III in HDL, and biotin-labelled apoCs and apoE were preferentially transferred to the larger HDL3 rather than HDL2. Adding a CETP inhibitor had no effect on these apoC transfers, indicating the process occurs independently of CETP. Quantifying apoC-II and apoC-III in HDL2 and HDL3 from eight healthy subjects showed large individual variation between the two apolipoproteins. The authors conclude apoC-II and apoC-III transfer disproportionately to HDL3 by a CETP-independent mechanism that may shape individual triglyceride metabolism.
Original abstract
Triglyceride hydrolysis by lipoprotein lipase (LPL), regulated by apolipoproteins C-II (apoC-II) and C-III (apoC-III), is essential for maintaining normal lipid homeostasis. During triglyceride lipolysis, the apoCs are known to be transferred from very low-density lipoprotein (VLDL) to high-density lipoprotein (HDL), but the detailed mechanisms of this transfer remain unclear. In this study, we investigated the extent of the apoC transfers and their distribution in HDL subfractions, HDL2 and HDL3. Each HDL subfraction was incubated with VLDL or biotin-labeled VLDL, and apolipoproteins and lipids in the re-isolated HDL were quantified using western blotting and high-performance liquid chromatography (HPLC). In consequence, incubation with VLDL showed the increase of net amount of apoC-II and apoC-III in the HDL. HPLC analysis revealed that the biotin-labeled apolipoproteins, including apoCs and apolipoprotein E, were preferably transferred to the larger HDL3. No effect of cholesteryl ester transfer protein inhibitor on the apoC transfers was observed. Quantification of apoCs levels in HDL2 and HDL3 from healthy subjects (n = 8) showed large individual differences between apoC-II and apoC-III levels. These results suggest that both apoC-II and apoC-III transfer disproportionately from VLDL to HDL2 and the larger HDL3, and these transfers might be involved in individual triglyceride metabolism.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.