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

Journal of Lipid Research

Hussein Yassine¹  Peter D. Reaven²  Dobrin Nedelkov²  Shripad Sinari²  Frances T. Yen³  Juraj Koska⁴  Randall W. Nelson⁵  Dawn C. Schwenke⁵  Olgica Trenchevska⁶  Dean Billheimer⁷ 

[1] Phoenix Veterans Affairs Health Care System, Phoenix, AZ;Arizona State University, Tempe, AZ;Phoenix Veterans Affairs Health Care System, Phoenix, AZ;To whom correspondence should be addressed;University of Arizona, Tucson, AZ;University of Southern California, Los Angeles, CA;Université de Lorraine, URAFPA, INSERM, Vandoeuvre-lès-Nancy, France;

关键词: lipoproteins;    mass spectrometry;    proteomics;    triglycerides;    very low density lipoprotein;   

DOI  :  

来源: DOAJ

【 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.

【 授权许可】

Unknown