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

18 Citations (Scopus)

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 1 2016

Fingerprint

Apolipoprotein C-III
Apolipoproteins C
Prediabetic State
Lipids
pioglitazone
Medical problems
Plasmas
Type 2 Diabetes Mellitus
Triglycerides
Peroxisome Proliferator-Activated Receptors
Glucose Intolerance
Hypertriglyceridemia
Lipolysis
Hep G2 Cells
N-Acetylneuraminic Acid

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

Koska, J., Yassine, H., Trenchevska, O., Sinar, S., Schwenke, D. C., Yen, F. T., ... 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

Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes1. / Koska, Juraj; Yassine, Hussein; Trenchevska, Olgica; Sinar, Shripad; Schwenke, Dawn C.; Yen, Frances T.; Billheimer, Dean; Nelson, Randall W.; Nedelkov, Dobrin; Reaven, Peter D.

In: Journal of Lipid Research, Vol. 57, No. 5, 01.05.2016, p. 894-905.

Research output: Contribution to journalArticle

Koska, J, Yassine, H, Trenchevska, O, Sinar, S, Schwenke, DC, Yen, FT, Billheimer, D, Nelson, RW, Nedelkov, D & Reaven, PD 2016, 'Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes1', Journal of Lipid Research, vol. 57, no. 5, pp. 894-905. https://doi.org/10.1194/jlr.P064816
Koska, Juraj ; Yassine, Hussein ; Trenchevska, Olgica ; Sinar, Shripad ; Schwenke, Dawn C. ; Yen, Frances T. ; Billheimer, Dean ; Nelson, Randall W. ; Nedelkov, Dobrin ; Reaven, Peter D. / Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes1. In: Journal of Lipid Research. 2016 ; Vol. 57, No. 5. pp. 894-905.
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