Apolipoprotein C-III isoforms: kinetics and relative implication in lipid metabolism.
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 A (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.
Institute on Nutraceuticals and Functional Foods, Laval University, Québec, Canada.
Jean-François
JF
Mauger
Patrick
P
Couture
Nathalie
N
Bergeron
Benoît
B
Lamarche
D000328:Adult; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D050356:Lipid Metabolism / Q000502:physiology*; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000097:blood / Q000378:metabolism / Q000502:physiology; D013223:Statistics as Topic
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D020033:Protein Isoforms; D002784:Cholesterol