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

Persistent Link:
http://hdl.handle.net/10150/614755
Title:
Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes
Author:
Koska, Juraj; Yassine, Hussein; Trenchevska, Olgica; Sinari, Shripad; Schwenke, Dawn C.; Yen, Frances T.; Billheimer, Dean; Nelson, Randall W.; Nedelkov, Dobrin; Reaven, Peter D.
Affiliation:
Univ Arizona
Issue Date:
2016-05
Publisher:
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation:
Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes 2016, 57 (5):894 Journal of Lipid Research
Journal:
Journal of Lipid Research
Rights:
Copyright © 2016 American Society for Biochemistry and Molecular Biology
Collection Information:
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
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.
Note:
Publisher's version/PDF may be used after 12 months embargo
ISSN:
0022-2275; 1539-7262
DOI:
10.1194/jlr.P064816
Keywords:
lipoproteins; mass spectrometry; proteomics; triglycerides; very low density lipoprotein
Version:
Final published version
Sponsors:
This work was supported by the National Institutes of Health Grants R24-DK090958 (R.W.N./P.D.R.), R01-067690 (P.D.R.), R01-HL94775 (P.D.R.), R01-DK082542 (R.W.N.), and K23-HL107389 and 15BGIA25690024 from the American Heart Association (H.Y.), the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development (#431), and Takeda Pharmaceuticals. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Additional Links:
http://www.jlr.org/lookup/doi/10.1194/jlr.P064816; http://www.jlr.org/content/suppl/2016/03/03/jlr.P064816.DC1.html

Full metadata record

DC FieldValue Language
dc.contributor.authorKoska, Jurajen
dc.contributor.authorYassine, Husseinen
dc.contributor.authorTrenchevska, Olgicaen
dc.contributor.authorSinari, Shripaden
dc.contributor.authorSchwenke, Dawn C.en
dc.contributor.authorYen, Frances T.en
dc.contributor.authorBillheimer, Deanen
dc.contributor.authorNelson, Randall W.en
dc.contributor.authorNedelkov, Dobrinen
dc.contributor.authorReaven, Peter D.en
dc.date.accessioned2016-06-24T22:40:43Z-
dc.date.available2016-06-24T22:40:43Z-
dc.date.issued2016-05-
dc.identifier.citationDisialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes 2016, 57 (5):894 Journal of Lipid Researchen
dc.identifier.issn0022-2275-
dc.identifier.issn1539-7262-
dc.identifier.doi10.1194/jlr.P064816-
dc.identifier.urihttp://hdl.handle.net/10150/614755-
dc.description.abstractThe 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.en
dc.description.sponsorshipThis work was supported by the National Institutes of Health Grants R24-DK090958 (R.W.N./P.D.R.), R01-067690 (P.D.R.), R01-HL94775 (P.D.R.), R01-DK082542 (R.W.N.), and K23-HL107389 and 15BGIA25690024 from the American Heart Association (H.Y.), the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development (#431), and Takeda Pharmaceuticals. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.en
dc.language.isoenen
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INCen
dc.relation.urlhttp://www.jlr.org/lookup/doi/10.1194/jlr.P064816en
dc.relation.urlhttp://www.jlr.org/content/suppl/2016/03/03/jlr.P064816.DC1.htmlen
dc.rightsCopyright © 2016 American Society for Biochemistry and Molecular Biologyen
dc.subjectlipoproteinsen
dc.subjectmass spectrometryen
dc.subjectproteomicsen
dc.subjecttriglyceridesen
dc.subjectvery low density lipoproteinen
dc.titleDisialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetesen
dc.typeArticleen
dc.contributor.departmentUniv Arizonaen
dc.identifier.journalJournal of Lipid Researchen
dc.description.notePublisher's version/PDF may be used after 12 months embargoen
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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