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. 2010 Feb;30(2):239-45.
doi: 10.1161/ATVBAHA.109.197830. Epub 2009 Nov 12.

Metabolism of very-low-density lipoprotein and low-density lipoprotein containing apolipoprotein C-III and not other small apolipoproteins

Carlos O Mendivil  1 , Chunyu Zheng, Jeremy Furtado, Julian Lel, Frank M Sacks
Affiliations

Metabolism of very-low-density lipoprotein and low-density lipoprotein containing apolipoprotein C-III and not other small apolipoproteins

Carlos O Mendivil et al. Arterioscler Thromb Vasc Biol. 2010 Feb.

Erratum in

  • Arterioscler Thromb Vasc Biol.2010 Sep;30(9):e171

Abstract

Objective: We aimed to clarify the influence of apolipoprotein C-III (apoCIII) on human apolipoprotein B metabolism.

Methods and results: We studied the kinetics of 4 very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) types containing: (1) otherApos-CIII-: none of apoCIII, apoAII, apoCI, apoCII, or apoE; (2) otherApos+CIII-: no apoCIII but at least one of the others; (3) otherApos-CIII+: apoCIII, but not any others; and (4) otherApos+CIII+: apoCIII and at least one other. VLDL and IDL otherApos-CIII+ and otherApos-CIII- had similar rates of lipolytic conversion to smaller particles. However, light LDL otherApos-CIII+ compared with otherApos-CIII- had much faster conversion to dense LDL as did light LDL otherApos+CIII+ compared with otherApos+CIII-. VLDL and IDL otherApos-CIII+ had minimal direct removal from circulation, whereas VLDL and IDL otherApos+CIII-, rich in apoE, showed fast clearance. Lipoproteins in fraction otherApos+CIII+ also rich in apoE had very low clearance.

Conclusions: The results suggest that apoCIII strongly inhibits hepatic uptake of VLDL and IDL overriding the opposite influence of apoE when both are present. The presence of apoCIII on dense VLDL is not associated with slow conversion to IDL, a lipoprotein lipase-dependent process; but when on light LDL, apoCIII is associated with enhanced conversion to dense LDL, a process involving hepatic lipase.

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Conflict of interest statement

Disclosures

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
ApoB metabolism in the study participants. Oval boxes represent apoB lipoprotein fractions separated by apolipoprotein composition and density, and numbers inside indicate pool sizes estimated by the model (mg). The measured pool sizes are shown in Supplemental Table II and Supplemental Figure III. The large square box in the left represents the liver; arrows out of this box represent direct liver secretion. Arrows out of lipoprotein compartments represent conversion to more dense lipoproteins and direct removal from plasma. Panel A. Numbers above or next to the arrows represent rate constants ± SD. Panel B. Percentages in bold next to the arrows indicate the percentage of total liver secretion into each fraction ± SD; percentages above the arrows indicate the relative proportion of flux out of each compartment. OtherApos−CIII−, lipoproteins without apoAII, apoCI, apoCII, apoCIII or apoE; OtherApos+CIII−, lipoproteins with apoAII or apoCI or apoCII or apoE and without apoCIII; OtherApos−CIII+, lipoproteins with no apoAII, no apoCI, no apoCII and no apoE but with apoCIII; OtherApos+CIII+, lipoproteins with apoCIII and at least one of the others.
Figure 2
Figure 2
Tracer-tracee ratios of D3-leucine (A) and D5-phenylalanine (B) in VLDL, IDL, and LDL subfractions in the study participants. Data points represent average leucine and phenylalanine tracer-tracee ratios. Lines represent model-derived curves fitted to the data. Phenylalanine data are presented on a logarithmic scale. See Figure 1 for explanation of lipoprotein fractions.
Figure 3
Figure 3
Rate of lipolytic catabolism of dense VLDL to IDL, and of light LDL to dense LDL according to apolipoprotein composition. Bars represent the average rate among study participants, error bars represent SD.
Figure 4
Figure 4
Proportion of total plasma LDL coming from direct liver secretion and lipolysis of VLDL and IDL with apoCIII in participants with fasting plasma triglycerides below or above the group median (1.35 mmol/L).
See this image and copyright information in PMC

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