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J. Lipid Res.
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A more recent version of this article appeared on June 1, 2006

Papers In Press, published online ahead of print February 22, 2006
J. Lipid Res., doi:10.1194/jlr.M500455-JLR200
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Submitted on October 18, 2005
Revised on February 1, 2006
Accepted on February 21, 2006

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

Jean-Francois Mauger, Patrick Couture, Nathalie Bergeron, and Benoît Lamarche

Institute on Nutraceuticals and Functional Food, Ste-Foy, Quebec G1K 7P4

Corresponding Author: jean-francois.mauger{at}inaf.ulaval.ca

Apolipoprotein C-III (apoC-III) production rate (PR) is strongly correlated to 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 isoforms 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 yrs, body mass index 29.8±4.6 kg/m2] using a primed-constant infusion of L-(5,5,5-D3) leucine for 12 hours. Mono-sialylated and di-sialylated apoC-III (ApoC-III1 and apoC-III2) exhibited similar PR (means±SD, 1.22±0.49 mg/kg/d vs. 1.15±0.59 mg/kg/d respectively) and similar fractional catabolic rate (FCR, 0.51±0.13 pool/d vs. 0.61±0.24 pool/d respectively). Non-sialylated apoC-III (ApoC-III0) had an 80% lower PR (0.25±0.12 mg/kg/d) and a 60% lower FCR (0.21±0.07 pool/d) (P<0.0001 for comparison with apoC-III1 and apoC-III2 isoforms). The PR of apoC-III1 and apoC-III2 were more strongly correlated with plasma TG levels (r>0.8, P<0.0001) than 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 apoC-III1 and apoC-III2 isoforms, contribute to hypertriglyceridemia and that apoC-III2 may play a significant role in the expression of the small dense LDL phenotype.


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