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Journal of Lipid Research, Vol. 43, 1680-1687, October 2002 Plasma kinetics of VLDL and HDL apoC-I in normolipidemic and hypertriglyceridemic subjects
* Hyperlipidemia and Atherosclerosis Research Group, Montréal, Québec, Canada
1 To whom correspondence should be addressed. e-mail: cohnj{at}ircm.qc.ca ApoC-I has several different lipid-regulating functions including, inhibition of receptor-mediated uptake of plasma triglyceride-rich lipoproteins, inhibition of cholesteryl ester transfer activity, and mediation of tissue fatty acid uptake. Since little is known about the rate of production and catabolism of plasma apoC-I in humans, the present study was undertaken to determine the plasma kinetics of VLDL and HDL apoC-I using a primed constant (12 h) intravenous infusion of deuterium-labeled leucine. Data were obtained for 14 subjects: normolipidemics (NL, n = 4), hypertriglyceridemics (HTG, n = 4) and combined hyperlipidemics (CHL, n = 6). Plasma VLDL triglyceride (TG) levels were 0.59 ± 0.03, 4.32 ± 0.77 (P < 0.01 vs. NL), and 2.20 ± 0.39 mmol/l (P < 0.01 vs. NL), and plasma LDL cholesterol (LDL-C) levels were 2.34 ± 0.22, 2.48 ± 0.26, and 5.35 ± 0.48 mmol/l (P < 0.01 vs. NL), respectively. HTG and CHL had significantly (P < 0.05) increased levels of total plasma apoC-I (12.5 ± 1.2 and 12.4 ± 1.3 mg/dl, respectively) versus NL (7.9 ± 0.6 mg/dl), due to significantly (P < 0.01) elevated levels of VLDL apoC-I (5.8 ± 0.8 and 4.5 ± 0.8 vs. 0.3 ± 0.1 mg/dl). HTG and CHL also had increased rates of VLDL apoC-I transport (i.e., production) versus NL: 2.29 ± 0.34 and 3.04 ± 0.53 versus 0.24 ± 0.11 mg/kg.day (P < 0.01), with no significant change in VLDL apoC-I residence times (RT): 1.16 ± 0.12 versus 0.69 ± 0.06 versus 0.74 ± 0.17. Although HDL apoC-I concentrations were not significantly lower in HTG and CHL versus NL, HDL apoC-I rates of transport were inversely related to plasma and VLDL-TG levels (r = -0.63 and -0.62, respectively, P < 0.05). Our results demonstrate that increased levels of plasma and VLDL apoC-I in hypertriglyceridemic subjects (with or without elevated LDL-C levels) are associated with increased levels of plasma VLDL apoC-I production.
Abbreviations: apo, apolipoprotein; CHL, combined hyperlipidemic(s); FTR, fractional transport rate; GC-MS, gas chromatography-mass spectrometry; HTG, hypertriglyceridemic(s); NL, normolipidemic(s); RT, residence time; TG, triglyceride; TR, transport rate; TRL, triglyceride-rich lipoprotein Supplementary key words triglyceride cholesterol atherosclerosis stable isotope lipoprotein metabolism
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