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

Abstract

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 CIII 2 isoforms, contribute to hypertriglyceridemia and that apoC-III 2 may play a significant role in the expression of the small, dense LDL phenotype. Copyright © 2006 by the American Society for Biochemistry and Molecular Biology, Inc.