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Journal of Lipid Research, Vol. 47, 1212-1218, June 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Apolipoprotein C-III isoforms: kinetics and relative implication in lipid metabolism

Jean-François Mauger^*, Patrick Couture, Nathalie Bergeron and Benoît Lamarche^1,*

^* Institute on Nutraceuticals and Functional Foods, Laval University, Québec, Canada
Department of Food Sciences and Nutrition, Laval University, Québec, Canada
Lipid Research Center, Laval University Medical Center, Québec, Canada

Published, JLR Papers in Press, February 22, 2006.

¹ To whom correspondence should be addressed. e-mail: benoit.lamarche{at}inaf.ulaval.ca

Apolipoprotein C-III (apoC-III) production rate (PR) is strongly correlated with plasma triglyceride (TG) levels. ApoC-III exists in three different isoforms, according to the sialylation degree of the protein. We investigated the kinetics and respective role of each apoC-III isoform in modulating intravascular lipid/lipoprotein metabolism. ApoC-III kinetics were measured in a sample of 18 healthy men [mean age (±SD) 42.1 ± 9.5 years, body mass index 29.8 ± 4.6 kg/m²] using a primed-constant infusion of L-(5,5,5-D3) leucine for 12 h. Mono-sialylated and di-sialylated apoC-III (apo-CIII₁ and apoC-III₂) exhibited similar PRs (means ± SD, 1.22 ± 0.49 mg/kg/day vs. 1.15 ± 0.59 mg/kg/day, respectively) and similar fractional catabolic rates (FCRs) (0.51 ± 0.13 pool/day vs. 0.61 ± 0.24 pool/day, respectively). Nonsialylated apoC-III (apoC-III₀) had an 80% lower PR (0.25 ± 0.12 mg/kg/day) and a 60% lower FCR (0.21 ± 0.07 pool/day) (P < 0.0001 for comparison with CIII₁ and CIII₂ isoforms). The PRs of apoC-III₁ and apoC-III₂ were more strongly correlated with plasma TG levels (r > 0.8, P < 0.0001) than was apoC-III₀ PR (r = 0.54, P < 0.05). Finally, the PR of apoC-III₂ was strongly correlated with the proportion of LDL <255 Å (r = 0.72, P = 0.002). These results suggest that all apoC-III isoforms, especially the predominant CIII₁ and CIII₂ isoforms, contribute to hypertriglyceridemia and that apoC-III₂ may play a significant role in the expression of the small, dense LDL phenotype.

Abbreviations: apoC-III, apolipoprotein C-III; BMI, body mass index; FCR, fractional catabolic rate; HDL-C, HDL-cholesterol; LPL, lipoprotein lipase; PR, production rate; PS, pool size; TG, triglyceride; TRL, triglyceride-rich lipoprotein

Supplementary key words VLDL metabolism • metabolic syndrome • triglycerides • LDL particle size • sialylation

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