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Changes in low-density lipoprotein electronegativity and oxidizability after aerobic exercise are related to the increase in associated non-esterified fatty acids

      Abstract

      The immediate effects of intense aerobic exercise on the composition and oxidizability of low- (LDL) and high-density lipoproteins (HDL) were studied in 11 male athletes. Plasma parameters known to affect lipoprotein oxidizability were also evaluated. Lipophilic antioxidants, including α-tocopherol and carotenoids, paraoxonase and malondialdehyde (MDA) in plasma remained unchanged after exercise. Increases in the concentration of uric acid, bilirubin and ascorbic acid after the race resulted in a significant increase in total antioxidant serum capacity. LDL, but not HDL, increased its ‘in vitro’-induced susceptibility to oxidation and the proportion of electronegative LDL (LDL(−)). The ability of HDL to inhibit the oxidation of LDL remained unchanged after exercise. The enhanced oxidizability of LDL was not explained by increments in its aldehyde content or by decrements in antioxidants. The major compositional change in LDL was an increase in non-esterified fatty acid (NEFA) content (from 4.00±1.24 to 19.00±14.18 mol NEFA/mol apoB). NEFA also increased in plasma and HDL. ‘In vitro’ experiments showed that incubation of LDL with increasing amounts of NEFA induced a concentration-dependent increase in the proportion of LDL(−). Moreover, a slightly increased NEFA content in LDL (15–50 mol NEFA/mol apoB) induced higher susceptibility to oxidation. These ‘in vitro’ results concur with those observed in LDL obtained from athletes after exercise, i.e. a concentration of approximately 20 mol NEFA/mol apoB increased LDL oxidizability and LDL(−) proportion. We conclude that changes in the qualitative characteristics of LDL after exercise were unrelated to oxidative stress, but were related to the increase in LDL-associated NEFA content.

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      References

        • Powell K.E.
        • Thompson P.D.
        • Caspersen C.J.
        • Kendrick J.S.
        Physical activity and the incidence of coronary heart disease.
        Annu. Rev. Public Health. 1987; 8: 253-287
        • Williams P.T.
        • Krauss R.M.
        • Wood P.D.
        • Lindgren F.T.
        • Giotas C.
        • Vranizan K.M.
        Lipoprotein subfractions of runners and sedentary men.
        Metabolism. 1986; 35: 45-52
        • Sánchez-Quesada J.L.
        • Ortega H.
        • Payés-Romero A.
        • et al.
        LDL from aerobically-trained subjects shows higher resistance to oxidative modification than LDL from sedentary subjects.
        Atherosclerosis. 1997; 132: 207-213
        • Shern-Brewer R.
        • Santanam N.
        • Wetzstein C.
        • White-Welkley J.
        • Parthasarathy S.
        Exercise and cardiovascular disease. A new perspective.
        Arterioscler. Thromb. Vasc. Biol. 1998; 18: 1181-1187
        • Gutteridge J.M.
        Lipid peroxidation and antioxidants as biomarkers of tissue damage.
        Clin. Chem. 1995; 41: 1819-1828
        • Steinberg D.
        • Parthasarathy S.
        • Carew T.E.
        • Khoo J.C.
        • Witztum J.L.
        Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity.
        New Engl. J. Med. 1989; 320: 915-924
        • Sánchez-Quesada J.L.
        • Homs-Serradesanferm R.
        • Serrat-Serrat J.
        • Serra-Grima J.R.
        • González-sastre F.
        • Ordóñez-Llanos J.
        Increase of LDL susceptibility to oxidation occurring after intense, long duration aerobic exercise.
        Atherosclerosis. 1995; 118: 297-305
        • Sánchez-Quesada J.L.
        • Jorba O.
        • Payés A.
        • et al.
        Ascorbic acid inhibits the increase in low-density lipoprotein (LDL) susceptibility to oxidation and the proportion of electronegative LDL induced by intense aerobic exercise.
        Coronary Artery Dis. 1998; 9: 249-255
        • Liu M.L.
        • Bergholm R.
        • Makimattila S.
        • et al.
        A marathon run increases the susceptibility of LDL to oxidation in vitro and modifies plasma antioxidants.
        Am. J. Physiol. 1999; 276: E1083-E1091
        • Wetzstein C.J.
        • Shern-Brewer R.A.
        • Santanam N.
        • Green N.R.
        • White-Welkley J.E.
        • Parthasarathy S.
        Does acute exercise affect the susceptibility of low density lipoprotein to oxidation?.
        Free Radic. Biol. Med. 1998; 24: 679-682
        • Hodis H.N.
        • Kramsch D.M.
        • Avogaro P.
        • et al.
        Biochemical and cytotoxic characteristics of an in vivo circulating oxidized low density lipoprotein (LDL−).
        J. Lipid Res. 1994; 35: 669-777
        • Demuth K.
        • Myara I.
        • Chappey B.
        • et al.
        A cytotoxic electronegative LDL subfraction is present in human plasma.
        Arterioscler. Thromb. Vasc. Biol. 1996; 16: 773-783
        • de Castellarnau C.
        • Sánchez-Quesada J.L.
        • Benı́tez S.
        • et al.
        Electronegative LDL from normolipemic subjects induces IL-8 and monocyte chemotactic protein secretion by human endothelial cells.
        Arterioscler. Thromb. Vasc. Biol. 2000; 20: 2281-2287
        • Vasankari T.J.
        • Kujala U.M.
        • Vasankari T.M.
        • Vuorimaa T.
        • Ahotupa M.
        Effects of acute prolonged exercise on serum and LDL oxidation and antioxidant defences.
        Free Radic. Biol. Med. 1997; 22: 509-513
        • Ginsburg G.S.
        • Agil A.
        • O'Toole E.M.
        • Rimm E.
        • Douglas P.S.
        • Rifai N.
        Effects of a single bout of ultraendurance exercise on lipid levels and susceptibility of lipids to peroxidation in triathletes.
        J. Am. Med. Assoc. 1996; 276: 221-232
        • Kretzschmar M.
        • Müller D.
        Aging, training and exercise. A review of effects on plasma glutathione and lipid peroxides.
        Sports Med. 1993; 15: 196-209
        • Viguie C.A.
        • Frei B.
        • Shigenaga M.K.
        • Ames B.N.
        • Packer L.
        • Brooks G.A.
        Antioxidant status and indexes of oxidative stress during consecutive days of exercise.
        J. Appl. Physiol. 1993; 75: 566-572
        • Kanter M.M.
        • Nolte L.A.
        • Holloszy J.O.
        Effects of an antioxidant vitamin mixture on lipid peroxidation at rest and postexercise.
        J. Appl. Physiol. 1993; 74: 965-969
        • Gohil K.
        • Vigue C.
        • Stanley W.C.
        • Brookes G.A.
        • Packer L.
        Blood glutathione oxidation during human exercise.
        J. Appl. Pharmacol. 1988; 64: 115-119
        • Hellstein Y.
        • Tullson P.C.
        • Richter E.A.
        • Bangsbo J.
        Oxidation of urate in human skeletal muscle during exercise.
        Free Radic. Biol. Med. 1997; 22: 169-174
        • Tribble D.L.
        Lipoprotein oxidation in dyslipemia: insights into general mechanisms affecting lipoprotein oxidative behavior.
        Curr. Opin. Lipidol. 1995; 6: 196-208
        • Ordóñez-Llanos J.
        • Serra-Grima J.R.
        • Mercé-Muntañola J.
        • González-Sastre F.
        Ratio of creatine kinase 2 mass concentration to total creatine kinase activity not altered by heavy physical exercise.
        Clin. Chem. 1992; 38: 2224-2247
        • Fukunaga K.
        • Suzuki T.
        • Takama K.
        Highly sensitive high-performance liquid chromatography for the measurement of malondialdehyde in biological samples.
        J. Chromatogr. 1993; 621: 77-78
        • Elinder L.S.
        • Walldius G.
        Simultaneous measurement of serum probucol and lipid-soluble antioxidants.
        J. Lipid Res. 1992; 33: 131-137
        • Aviram M.
        • Billecke S.
        • Sorenson R.
        • et al.
        Paraoxonase active site required for protection against LDL oxidation involves its free sulfhydryl group and is different from that required for its arylesterase/paraoxonase activities.
        Arterioscler. Thromb. Vasc. Biol. 1998; 18: 1617-1624
        • Greenleaf J.E.
        • Convertino V.A.
        • Mangseth G.R.
        Plasma volume during stress in man: osmolality and red cell volume.
        J. Appl. Physiol. 1979; 47: 1031-1038
        • Havel R.J.
        • Eder H.A.
        • Bragdon J.H.
        The distribution and chemical composition of ultracentrifugally-separated lipoproteins in human serum.
        J. Clin. Invest. 1955; 34: 1345-1353
        • Sánchez-Quesada J.L.
        • Pérez A.
        • Caixàs A.
        • et al.
        Electronegative low density lipoprotein subform is increased in short-duration IDDM patients and is closely related to glycaemic control.
        Diabetologia. 1996; 39: 1469-1476
        • Esterbauer H.
        • Striegl G.
        • Puhl H.
        • Rotheneder M.
        Continuous monitoring of in vitro oxidation of human low density lipoprotein.
        Free Radic. Res. Commun. 1989; 6: 67-75
        • Vedie B.
        • Myara I.
        • Pech M.A.
        • et al.
        Fractionation of charge-modified low density lipoprotein by fast protein liquid chromatography.
        J. Lipid Res. 1991; 32: 1359-1369
        • Bailey A.L.
        • Wortley G.
        • Southon S.
        Measurement of aldehydes in low-density lipoprotein by high performance liquid chromatography.
        Free Radic. Biol. Med. 1997; 23: 1078-1085
        • Esterbauer H.
        • Jürgens G.
        • Quehenberger O.
        • Koller E.
        Autoxidation of human low density lipoprotein: loss of polyunsaturated fatty acids and vitamin E and generation of aldehydes.
        J. Lipid Res. 1987; 28: 495-509
        • Bijnen F.C.
        • Caspersen D.J.
        • Mosterd W.L.
        Physical inactivity as a risk factor for coronary heart disease: a WHO and International Society and Federation of Cardiology Position Statement.
        Bull. World Health Organ. 1994; 72: 1-4
        • Baumstark M.W.
        • Frey I.
        • Berg A.
        Acute and delayed effects of prolonged exercise on serum lipoproteins: concentration and composition of low-density lipoprotein subfractions and very low-density lipoprotein.
        Eur. J. Appl. Physiol. 1993; 66: 526-530
      1. Brooks G.A. Fahey T. Exercise Physiology. Human Bioenergetics and its Application. Mcmillan, New York1984: 338-364
        • Bowry V.W.
        • Stanley K.K.
        • Stocker R.
        High density lipoprotein is the major carrier of lipid hydroperoxides in human blood plasma from fasting donors.
        Proc. Natl. Acad. Sci. USA. 1992; 89: 10316-10320
        • Mackness M.I.
        • Abbott C.
        • Arrol S.
        • Durrington P.N.
        The role of high density lipoprotein and lipid-soluble antioxidant vitamins in inhibiting low-density lipoprotein oxidation.
        Biochem. J. 1993; 294: 829-834
        • Lamon-Fava S.
        • McNamara J.R.
        • Farber H.W.
        • Hill N.S.
        • Schaefer E.J.
        Acute changes in lipid, lipoprotein, apolipoprotein, and low-density lipoprotein particle size after an endurance triathlon.
        Metabolism. 1989; 38: 921-928
        • Shafrir E.
        Partition of unesterified fatty acid in normal and nephrotic syndrome serum and its effect on serum electrophoresic pattern.
        J. Clin. Invest. 1958; 37: 1775-1782
        • Cistola D.P.
        • Small D.M.
        Fatty acid distribution in systems modeling the normal and diabetic human circulation: a 13C nuclear magnetic resonance study.
        J. Clin. Invest. 1991; 87: 1431-1441
        • Chung B.H.
        • Tallis G.A.
        • Cho B.H.S.
        • Segrest J.P.
        • Henkins Y.
        Lipolysis-induced partitioning of free fatty acids to lipoproteins: effect on the biological properties of free fatty acids.
        J. Lipid Res. 1995; 36: 1956-1970
        • Carlsson M.
        • Wessman Y.
        • Almgren P.
        • Groop L.
        High levels of nonesterified fatty acids are associated with increased familial risk of cardiovascular disease.
        Arterioscler. Thromb. Vasc. Biol. 2000; 20: 1588-1594
        • Steinberg H.O.
        • Tarshoby M.
        • Monestel R.
        • et al.
        Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation.
        J. Clin. Invest. 1997; 100: 1230-1239
        • Chung B.H.
        • Hennig B.
        • Cho B.H.S.
        • Darnell B.E.
        Effect of the fat composition of a single meal on the composition and cytotoxic potencies of lipolytically-releasable free fatty acids in postprandial plasma.
        Atherosclerosis. 1998; 141: 321-332
        • Hennig B.
        • Toborek M.
        • Joshi-Barbe S.
        • et al.
        Linoleic acid activates nuclear transcription factor-kappaB (NF-kappaB) and induces NF-kappaB-dependent transcription in cultured endothelial cells.
        Am. J. Clin. Nutr. 1996; 63: 318-322
        • Hayashi H.
        • Naito C.
        • Ito H.
        • Kawamura M.
        • Miyazaki S.
        • Kumai M.
        Enhanced degradation of low density lipoprotein in human monocyte-derived macrophages associated with an increase in its free fatty acid content.
        Atherosclerosis. 1987; 66: 139-144
        • Aviram M.
        • Lund-Katz S.
        • Phillips M.C.
        • Chait A.
        The influence of the triglyceride content of low density lipoprotein on the interaction of apolipoprotein B-100 with cells.
        J. Biol. Chem. 1988; 263: 16842-16848
        • Braschi S.
        • Masson D.
        • Rostoker G.
        • et al.
        Role of lipoprotein-bound NEFAs in enhancing the specific activity of plasma CETP in the nephrotic syndrome.
        Arterioscler. Thromb. Vasc. Biol. 1997; 17: 2559-2567
        • Viens L.
        • Athias A.
        • Lizard G.
        • et al.
        Effect of lipid transfer activity and lipolysis on low density lipoprotein oxidizability: evidence for lipolysis-generated non-esterified fatty acids as inhibitors of LDL oxidation.
        J. Lipid Res. 1996; 37: 2179-2192
        • Upston J.M.
        • Neuzil J.
        • Witting P.K.
        • Alleva R.
        • Stocker R.
        Oxidation of free fatty acids in low density lipoprotein by 15-lipoxygenase stimulates nonenzymic, α-tocopherol-mediated peroxidation of cholesteryl esters.
        J. Biol. Chem. 1997; 272: 30067-30074
        • Foucher C.
        • Lagrost L.
        • Maupoil V.
        • le Meste M.
        • Rochette L.
        • Gambert P.
        Alterations of lipoprotein fluidity by non-esterified fatty acids known to affect cholesteryl ester transfer protein activity.
        Eur. J. Biochem. 1996; 236: 436-442
        • Hakala J.K.
        • Öörni K.
        • Ala-Korpela M.
        • Kovanen P.T.
        Lipolytic modification of LDL by phospholipase A2 induces particle aggregation in the absence and fusion in the presence of heparin.
        Arterioscler. Thromb. Vasc. Biol. 1999; 19: 1276-1283
        • Hermann M.
        • Gneimer B.
        Altered susceptibility to in vitro oxidation of LDL in LDL complexes and LDL aggregates.
        Arterioscler. Thromb. 1992; 12: 1503-1506