文章基本信息

标题：Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes
本地全文：下载
作者：Juraj Koska ; Hussein Yassine ; Olgica Trenchevska 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2016
卷号：57
期号：5
页码：894-905
DOI：10.1194/jlr.P064816
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：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.
关键词：lipoproteins ; mass spectrometry ; proteomics ; triglycerides ; very low density lipoprotein