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Clinical dyslipidaemia is associated with changes in the lipid composition and inflammatory properties of apolipoprotein-B-containing lipoproteins from women with type 2 diabetes.

Journal article
Authors Marcus Ståhlman
H T Pham
Martin Adiels
T W Mitchell
S J Blanksby
Björn Fagerberg
Kim Ekroos
Jan Borén
Published in Diabetologia
Volume 55
Issue 4
Pages 1156-66
ISSN 1432-0428
Publication year 2012
Published at Wallenberg Laboratory
Department of Mathematical Sciences
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 1156-66
Language en
Links dx.doi.org/10.1007/s00125-011-2444-...
Keywords Apolipoproteins B, metabolism, Diabetes Mellitus, Type 2, complications, metabolism, physiopathology, Dyslipidemias, complications, metabolism, physiopathology, Female, Humans, Inflammation, metabolism, physiopathology, Lipoproteins, LDL, metabolism, Lipoproteins, VLDL, metabolism, Middle Aged
Subject categories Clinical Medicine

Abstract

Aims/hypothesis The aim of this study was to use lipidomics to determine if the lipid composition of apolipoprotein-B-containing lipoproteins is modified by dyslipidaemia in type 2 diabetes and if any of the identified changes potentially have biological relevance in the pathophysiology of type 2 diabetes. Methods VLDL and LDL from normolipidaemic and dyslipidaemic type 2 diabetic women and controls were isolated and quantified with HPLC and mass spectrometry. A detailed molecular characterisation of VLDL triacylglycerols (TAG) was also performed using the novel ozone-induced dissociation method, which allowed us to distinguish vaccenic acid (C18:1 n-7) from oleic acid (C18:1 n-9) in specific TAG species. Results Lipid class composition was very similar in VLDL and LDL from normolipidaemic type 2 diabetic and control participants. By contrast, dyslipidaemia was associated with significant changes in both lipid classes (e.g. increased diacylglycerols) and lipid species (e.g. increased C16:1 and C20:3 in phosphatidylcholine and cholesteryl ester and increased C16:0 [palmitic acid] and vaccenic acid in TAG). Levels of palmitic acid in VLDL and LDL TAG correlated with insulin resistance, and VLDL TAG enriched in palmitic acid promoted increased secretion of proinflammatory mediators from human smooth muscle cells. Conclusions We showed that dyslipidaemia is associated with major changes in both lipid class and lipid species composition in VLDL and LDL from women with type 2 diabetes. In addition, we identified specific molecular lipid species that both correlate with clinical variables and are proinflammatory. Our study thus shows the potential of advanced lipidomic methods to further understand the pathophysiology of type 2 diabetes.

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