Abstract
Increased oxidative stress is associated with type-2 diabetes and related cardiovascular diseases, but oxidative modification of LDL has been partially characterized. Our aim was to compare the lipid and fatty acid composition as well as the redox status of LDL from diabetic patients and healthy subjects. First, to ensure that isolation of LDL by sequential ultracentrifugation did not result in lipid modifications, lipid composition and peroxide content were determined in LDL isolated either by ultracentrifugation or fast-protein liquid chromatography. Both methods resulted in similar concentrations of lipids, fatty acids, hydroxy-octadecadienoic acid (HODE) and malondialdehyde (MDA). Then, LDLs were isolated by ultracentrifugation from eight type-2 diabetic patients and eight control subjects. Compared to control LDL, diabetic LDL contained decreased cholesteryl esters and increased triglyceride concentrations. Ethanolamine plasmalogens decreased by 49%. Proportions of linoleic acid decreased in all lipid classes, while proportions of arachidonic acid increased in cholesteryl esters. Total HODE concentrations increased by 56%, 12- and 15-hydroxy-eicosatetraenoic acid by 161 and 86%, respectively, and MDA levels increased by twofold. α-Tocopherol concentrations, expressed relative to triglycerides, were lower in LDL from patients compared to controls, while γ-tocopherol did not differ. Overall, LDL from type-2 diabetic patients displayed increased oxidative stress. Determination of hydroxylated fatty acids and ethanolamine plasmalogen depletion could be especially relevant in diabetes.
Similar content being viewed by others
Abbreviations
- BHT:
-
Butylhydroxytoluene
- CE:
-
Cholesteryl ester
- DMA:
-
Dimethylacetal
- ELSD:
-
Evaporative light-scattering detector
- Etn-PL:
-
Ethanolamine phospholipids
- FPLC:
-
Fast-protein liquid chromatography
- GPE:
-
Glycerophosphoethanolamine
- HETE:
-
Hydroxy-eicosatetraenoic acid
- HODE:
-
Hydroxy-octadecadienoic acid
- MDA:
-
Malondialdehyde
- MUFA:
-
Monounsaturated fatty acids
- PC:
-
Phosphatidylcholine
- PL:
-
Phospholipid
- PUFA:
-
Polyunsaturated fatty acids
- SFA:
-
Saturated fatty acids
- SM:
-
Sphingomyelin
- TBA:
-
Thiobarbituric acid
- TBARS:
-
Thiobarbituric acid reactive species
- TG:
-
Triacylglycerols
- UC:
-
Ultracentrifugation
References
Mehta JL, Rasouli N, Sinha AK, Molavi B (2006) Oxidative stress in diabetes: a mechanistic overview of its effects on atherogenesis and myocardial dysfunction. Int J Biochem Cell Biol 38:794–803
Baynes JW (1991) Role of oxidative stress in development of complications in diabetes. Diabetes 40:405–412
Witztum JL, Steinberg D (1991) Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 88:1785–1792
Griesmacher A, Kindhauser M, Andert SE et al (1995) Enhanced serum levels of thiobarbituric-acid-reactive substances in diabetes mellitus. Am J Med 98:469–475
Gopaul NK, Anggard EE, Mallet AI, Betteridge DJ, Wolff SP, Nourooz-Zadeh J (1995) Plasma 8-epi-PGF2 alpha levels are elevated in individuals with non-insulin dependent diabetes mellitus. FEBS Lett 368:225–229
Bellomo G, Maggi E, Poli M, Agosta FG, Bollati P, Finardi G (1995) Autoantibodies against oxidatively modified low-density lipoproteins in NIDDM. Diabetes 44:60–66
Napoli C, Mancini FP, Corso G et al (1997) A simple and rapid purification procedure minimizes spontaneous oxidative modifications of low density lipoprotein and lipoprotein (a). J Biochem 121:1096–1101
Zambon A, Schmidt I, Beisiegel U, Brunzell JD (1996) Dimeric lipoprotein lipase is bound to triglyceride-rich plasma lipoproteins. J Lipid Res 37:2394–2404
Pruneta V, Autran D, Ponsin G et al (2001) Ex vivo measurement of lipoprotein lipase-dependent very low density lipoprotein (VLDL)-triglyceride hydrolysis in human VLDL: an alternative to the postheparin assay of lipoprotein lipase activity? J Clin Endocrinol Metab 86:797–803
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Seppanen-Laakso T, Laakso I, Vanhanen H, Kiviranta K, Lehtimaki T, Hiltunen R (2001) Major human plasma lipid classes determined by quantitative high-performance liquid chromatography, their variation and associations with phospholipid fatty acids. J Chromatogr B Biomed Sci Appl 754:437–445
Browne RW, Armstrong D (2000) HPLC analysis of lipid-derived polyunsaturated fatty acid peroxidation products in oxidatively modified human plasma. Clin Chem 46:829–836
Therasse J, Lemonnier F (1987) Determination of plasma lipoperoxides by high-performance liquid chromatography. J Chromatogr 413:237–241
Calzada C, Coulon L, Halimi D et al (2007) In vitro glycoxidized low-density lipoproteins and low-density lipoproteins isolated from type 2 diabetic patients activate platelets via p38 mitogen-activated protein kinase. J Clin Endocrinol Metab 92:1961–1964
Grundy SM, Cleeman JI, Daniels SR et al (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 112:2735–2752
Wiesner P, Leidl K, Boettcher A, Schmitz G, Liebisch G (2009) Lipid profiling of FPLC-separated lipoprotein fractions by electrospray ionization tandem mass spectrometry. J Lipid Res 50:574–585
Kuksis A, Myher JJ, Geher K, Breckenridge WC, Jones GJ, Little JA (1981) Lipid class and molecular species interrelationships among plasma lipoproteins of s subjects. J Chromatogr 224:1–23
Engelmann B, Brautigam C, Thiery J (1994) Plasmalogen phospholipids as potential protectors against lipid peroxidation of low density lipoproteins. Biochem Biophys Res Commun 204:1235–1242
Esterbauer H, Gebicki J, Puhl H, Jurgens G (1992) The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radic Biol Med 13:341–390
Barre E (2003) A more detailed fatty acid composition of human lipoprotein(a)—a comparison with low density lipoprotein. Chem Phys Lipids 123:99–105
Esterbauer H, Jurgens G, Quehenberger O, Koller E (1987) Autoxidation of human low density lipoprotein: loss of polyunsaturated fatty acids and vitamin E and generation of aldehydes. J Lipid Res 28:495–509
Scheek LM, Wiseman SA, Tijburg LB, van Tol A (1995) Dialysis of isolated low density lipoprotein induces a loss of lipophilic antioxidants and increases the susceptibility to oxidation in vitro. Atherosclerosis 117:139–144
Stephens JW, Khanolkar MP, Bain SC (2009) The biological relevance and measurement of plasma markers of oxidative stress in diabetes and cardiovascular disease. Atherosclerosis 202:321–329
Mora S, Otvos JD, Rosenson RS, Pradhan A, Buring JE, Ridker PM (2010) Lipoprotein particle size and concentration by nuclear magnetic resonance and incident type 2 diabetes in women. Diabetes 59:1153–1160
Feingold KR, Grunfeld C, Pang M, Doerrler W, Krauss RM (1992) LDL subclass phenotypes and triglyceride metabolism in non-insulin-dependent diabetes. Arterioscler Thromb 12:1496–1502
Packard CJ (2003) Triacylglycerol-rich lipoproteins and the generation of small, dense low-density lipoprotein. Biochem Soc Trans 31:1066–1069
Verges B (2009) Lipid modification in type 2 diabetes: the role of LDL and HDL. Fundam Clin Pharmacol 23:681–685
Tribble DL, Holl LG, Wood PD, Krauss RM (1992) Variations in oxidative susceptibility among six low density lipoprotein subfractions of differing density and particle size. Atherosclerosis 93:189–199
Jurgens G, Fell A, Ledinski G, Chen Q, Paltauf F (1995) Delay of copper-catalyzed oxidation of low density lipoprotein by in vitro enrichment with choline or ethanolamine plasmalogens. Chem Phys Lipids 77:25–31
Nagan N, Zoeller RA (2001) Plasmalogens: biosynthesis and functions. Prog Lipid Res 40:199–229
Niki E (2009) Lipid peroxidation: physiological levels and dual biological effects. Free Radic Biol Med 47:469–484
Mashima R, Onodera K, Yamamoto Y (2000) Regioisomeric distribution of cholesteryl linoleate hydroperoxides and hydroxides in plasma from healthy humans provides evidence for free radical-mediated lipid peroxidation in vivo. J Lipid Res 41:109–115
Liu W, Yin H, Akazawa YO, Yoshida Y, Niki E, Porter NA (2010) Ex vivo oxidation in tissue and plasma assays of hydroxyoctadecadienoates: Z, E/E, E stereoisomer ratios. Chem Res Toxicol 23:986–995
Brenner RR (2003) Hormonal modulation of delta6 and delta5 desaturases: case of diabetes. Prostaglandins Leukot Essent Fatty Acids 68:151–162
Kesavulu MM, Giri R, Kameswara Rao B, Apparao C (2000) Lipid peroxidation and antioxidant enzyme levels in type 2 diabetics with microvascular complications. Diabetes Metab 26:387–392
Schneider M, Verges B, Klein A et al (2004) Alterations in plasma vitamin E distribution in type 2 diabetic patients with elevated plasma phospholipid transfer protein activity. Diabetes 53:2633–2639
Hunt JV, Smith CC, Wolff SP (1990) Autoxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose. Diabetes 39:1420–1424
Acknowledgments
We thank the subject participants for their contribution. We also thank the nursing staff at the Hospices Civils de Lyon for their help with blood sample collection and some analyses. We acknowledge the French Ministry of Education and Research for RC’s grant. CC is supported by CNRS.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Colas, R., Pruneta-Deloche, V., Guichardant, M. et al. Increased Lipid Peroxidation in LDL from Type-2 Diabetic Patients. Lipids 45, 723–731 (2010). https://doi.org/10.1007/s11745-010-3453-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11745-010-3453-9