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J Lipid Res. 2016 May;57(5):894-905. doi: 10.1194/jlr.P064816. Epub 2016 Mar 3.

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

Author information

1
Phoenix Veterans Affairs Health Care System, Phoenix, AZ juraj.koska@va.gov.
2
University of Southern California, Los Angeles, CA.
3
Arizona State University, Tempe, AZ.
4
University of Arizona, Tucson, AZ.
5
Phoenix Veterans Affairs Health Care System, Phoenix, AZ.
6
Université de Lorraine, URAFPA, INSERM, Vandoeuvre-lès-Nancy, France.

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-III1 showed 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.

KEYWORDS:

lipoproteins; mass spectrometry; proteomics; triglycerides; very low density lipoprotein

PMID:
26945091
PMCID:
PMC4847634
DOI:
10.1194/jlr.P064816
[Indexed for MEDLINE]
Free PMC Article

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