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

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-(I)II2 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-gamma 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.
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Submitted on : Monday, August 21, 2017 - 11:30:42 AM
Last modification on : Monday, July 4, 2022 - 2:26:43 PM

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Juraj Koska, Hussein yassine, Olgica Trenchevska, Shripad Sinari, Dawn C. Schwenke, et al.. Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes. Journal of Lipid Research, American Society for Biochemistry and Molecular Biology, 2016, 57 (5), pp.894-905. ⟨10.1194/jlr.P064816⟩. ⟨hal-01575598⟩



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