Effects of apoA-II, C-I, C-II on in vivo metabolism of apoB-containing lipoproteins-stable, isotope study

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In addition to an elevated LDL-cholesterol (C), an increased triglyceride (TG) rich lipoprotein has drawn more attention as the risk for coronary artery disease. TG-rich lipoproteins (TRL) comprise heterogeneous lipoproteins subclasses, depending upon apoprotein composition. Among them, apoC-III and apoE have been extensively investigated, whereas effects of other apoptoteins such as apoA-II, C-I, C-II are largely unknown. In the present study, we wish to investigate 1) distribution of VLDL subcleasses which differ in apolipoprotein compositions, 2) in vivo role of apoC-III and apoE by utilyzing stable isotopically labeled amino acid tracer study. ApoA-II, C-I, and C-II containing VLDL comprise 13%, 17%, and 16% of VLDL, respectively, representing minor fractions among TRL relative to those containing either apoC-III or apoE. Those containing the apolipoproteins comprise more cholesterol and TG per particle and tend to have other apoproteins. Distribution does not change postprandially, but absolute concentrations increase by fat ingestion. In vivo kinetic study revealed that E-/C-and E-/C+ VLDL are catabolized faster than E+/C-and E+/C+ particles. This was true for IDL and LDL, too. ApoE containing particle, especially E+/C-, are preferentially catabolized by direct removal via LDL receptor or/and LRP with a delayed lipolysis. To the contrary, E-/C-and E-/C+ particles are catablized in favor of lipolysis rather than direct removal. In conclusions, these results demonstrated 1) that, unlike apoC-III and apoE, TRL containing apoA-II, apoC-I, or apoC-II represent minor fraction, thus not suitable for kinetic study. Combination of stable isotope tracer study with immunoaffinity isolation technique provides for the first time a new insight into the role of apoC-III and apoE on TRL, namely inhibitory effect of lipolysis and promoting direct uptake by apoE and promoting lipolysis by apoC-III.