Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes1

Juraj Koska, Hussein Yassine, Olgica Trenchevska, Shripad Sinar, Dawn C. Schwenke, Frances T. Yen, Dean Billheimer, Randall W. Nelson, Dobrin Nedelkov, Peter D. Reaven

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The apoC-III proteoform containing two sialic acid residues (apoC-III2) has different in vitro effects on lipid metabolism compared with asialylated (apoC-III0) or the most abundant monosialylated (apoC-III1) proteoforms. Cross-sectional and longitudinal associations between plasma apoC-III proteoforms (by mass spectrometric immunoassay) and plasma lipids were tested in two randomized clinical trials: ACT NOW, a study of pioglitazone in subjects with impaired glucose tolerance (n = 531), and RACED (n = 296), a study of intensive glycemic control and atherosclerosis in type 2 diabetes patients. At baseline, higher relative apoC-III2 and apoC-III2/apoC-III1 ratios were associated with lower triglycerides and total cholesterol in both cohorts, and with lower small dense LDL in the RACED. Longitudinally, changes in apoC-III2/apoC-III1 were inversely associated with changes in triglycerides in both cohorts, and with total and small dense LDL in the RACED. apoC-III2/apoC-III1 was also higher in patients treated with PPAR-γ agonists and was associated with reduced cardiovascular events in the RACED control group. Ex vivo studies of apoC-III complexes with higher apoC-III2/ apoC-III1showed attenuated inhibition of VLDL uptake by HepG2 cells and LPL-mediated lipolysis, providing possible functional explanations for the inverse association between a higher apoC-III2/apoC-III1 and hypertriglyceridemia, proatherogenic plasma lipid profiles, and cardiovascular risk.- Koska, J., H. Yassine, O. Trenchevska, S. Sinari, D. C. Schwenke, F. T. Yen, D. Billheimer, R. W. Nelson, D. Nedelkov, and P. D. Reaven. Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes. J. Lipid Res. 2016. 57: 894-905.

Original languageEnglish (US)
Pages (from-to)894-905
Number of pages12
JournalJournal of Lipid Research
Volume57
Issue number5
DOIs
StatePublished - May 2016

Keywords

  • Lipoproteins
  • Mass spectrometry
  • Proteomics
  • Triglycerides
  • Very low density lipoprotein

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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    Koska, J., Yassine, H., Trenchevska, O., Sinar, S., Schwenke, D. C., Yen, F. T., Billheimer, D., Nelson, R. W., Nedelkov, D., & Reaven, P. D. (2016). Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes1. Journal of Lipid Research, 57(5), 894-905. https://doi.org/10.1194/jlr.P064816