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Effects of dietary polyunsaturated fatty acids and hepatic steatosis on the functioning of isolated working rat heart under normoxic conditions and during post-ischemic reperfusion

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Abstract

The purpose of this study was to modify the amount of 22:4 n-6, 22:5 n-6 and 20:5 n-3 in cardiac phospholipids and to evaluate the influence of these changes on the functioning of working rat hearts and mitochondrial energy metabolism under normoxic conditions and during postischemic reperfusion. The animals were fed one of these four diets: (i) 10% sunflower seed oil (SSO); (ii) 10% SSO + 1% cholesterol; (iii) 5% fish oil (FO, EPAX 3000TG, Pronova) + 5% SSO; (iv) 5% FO + 5% SSO + 1% cholesterol. Feeding n-3 PUFA decreased n-6 PUFA and increased n-3 PUFA in plasma lipids. In the phospholipids of cardiac mitochondria, this dietary modification also induced a decrease in the n-6/n-3 PUFA ratio. Cholesterol feeding induced marked hepatic steatosis (HS) characterized by the whitish appearance of the liver. It also brought about marked changes in the fatty acid composition of plasma and mitochondrial phospholipids. These changes, characterized by the impairment of Δ5- and Δ6-desaturases, were more obvious in the SSO-fed rats, probably because of the presence of the precursor of the n-6 family (linoleate) in the diet whereas the FO diet contained large amounts of eicosapentaenoic and docosahexaenoic acids. In the mitochondrial phospholipids of SSO-fed rats, the (22:4 n-6 + 22:5 n-6) to 18:2 n-6 ratio was decreased by HS, without modification of the proportion of 20:4 n-6. In the mitochondrial phospholipids of FO-fed rats, the amount of 20:5 n-3 tended to be higher (+56%). Cardiac functioning was modulated by the diets. Myocardial coronary flow was enhanced by HS in the SSO-fed rats, whereas it was decreased in the FO-fed animals. The rate constant k012 representing the activity of the adenylate kinase varied in the opposite direction, suggesting that decreased ADP concentrations could cause oxygen wasting through the opening of the permeability transition pore. The recovery of the pump function tended to be increased by n-3 PUFA feeding (+22%) and HS (+45%). However, the release of ascorbyl free radical during reperfusion was not significantly modified by the diets. Conversely, energy production was increased by ischemia/reperfusion in the SSO group, whereas it was not modified in the FO group. This supports greater ischemia/reperfusion-induced calcium accumulation in the SSO groups than in the FO groups. HS did not modify the mitochondrial energy metabolism during ischemia/reperfusion. Taken together, these data suggest that HS- and n-3 PUFA-induced decrease in 22:4 and 22:5 n-6 and increase in 20:5 n-3 favor the recovery of mechanical activity during post-ischemic reperfusion.

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References

  1. Beare-Rogers JL, Nera EA: Nutritional effects of partially hydrogenated low erucic rapeseed oil. Lipids 12: 769–774, 1976

    Google Scholar 

  2. Swanson JE, Kinsella JE: Dietary n-3 polyunsaturated fatty acids: Modification of rat cardiac lipids and fatty acid composition. J Nutr 116: 514–523, 1986

    Google Scholar 

  3. Hock CE, Holahan MA, Reibel DK: Effect of dietary fish oil on myocardial phospholipids and myocardial ischemic damages. Am J Physiol 252: H554–H560, 1987

    Google Scholar 

  4. Nalbone G, Termine E, Leonardi J, Portugal H, Lechene P, Calaf R, Lafont R, Lafont H: Effect of dietary salmon oil feeding on rat heart lipid status. J Nutr 118: 809–817, 1988

    Google Scholar 

  5. Ruiz-Gutierrez V, Molina MT, Vazquez CM: Comparative effects of feeding different fats on fatty acid composition of major individual phospholipids of rat hearts. Ann Nutr Metab 34: 350–358, 1990

    Google Scholar 

  6. Demaison L, Sergiel JP, Moreau D, Grynberg A: Influence of the phospholipid n-6/n-3 polyunsaturated fatty acid ratio on the mitochondrial oxidative metabolism before and after myocardial ischemia. Biochim Biophys Acta 1227: 53–59, 1994

    Google Scholar 

  7. Demaison L, Grynberg A: Influence of dietary linseed oil and sunflower seed oil on some mechanical and metabolic parameters of isolated working rat hearts. Reprod Nutr Dev 31: 37–45, 1991

    Google Scholar 

  8. Demaison L, P Bouveret, Grynberg A: Polyunsaturated fatty acid composition and lipid metabolism in cultured cardiomyocyte and isolated working rat heart. Nutr Res 13: 1003–1015, 1993

    Google Scholar 

  9. Paulson DJ, Smith JM, Zhao J, Bowman J: Effects of dietary fish oil on myocardial ischemic/reperfusion injury of Wistar Kyoto and Stroke-Prone spontaneously hypertensive rats. Metabolism 41: 533–539, 1992

    Google Scholar 

  10. Demaison L, Sergiel JP, Moreau D, Grynberg A: Influence of dietary fish oil on the mechanical and biochemical function of isolated working rat hearts before and after ischemia. In: C.A. Drevon, I. Baksaas, H.E. Krokan (eds). Omega-3 Fatty Acids: Metabolism and Biological Effects. Birkhäuser Verlag, Basel, 1993, pp 115–123

    Google Scholar 

  11. Yang B, Saldeen TGP, Nichols WW, Mehta JL: Dietary fish oil supplementation attenuates myocardial dysfunction and injury caused by global ischemia and reperfusion in isolated rat hearts. J Nutr 123: 2067–2074, 1993

    Google Scholar 

  12. Yang BC, Saldeen TGP, Bryant JL, Nichols WW, Metha JL: Long-term dietary fish oil supplementation protects against ischemia-reperfusion-induced myocardial dysfunction in isolated rat hearts. Am Heart J 126: 1287–1292, 1993

    Google Scholar 

  13. Sentex E, Grynberg A, Sergiel JP, Demaison L: Influence of the phospholipid n-6:n-3 polyunsaturated fatty acid ratio on the oxidative phosphorylation of isolated cardiac mitochondria. Exp Clin Cardiol 1: 37–44, 1996

    Google Scholar 

  14. Mugge A: The role of reactive oxygen species in atherosclerosis. Z Kardiol 87: 851–864, 1998

    Google Scholar 

  15. Vergely C, Maupoil V, Benderitter M, Rochette L: Influence of the severity of myocardial ischemia on the intensity of ascorbyl free radical release and on postischemic recovery during reperfusion. Free Radic Biol Med 24: 470–479, 1998

    Google Scholar 

  16. Sergiel JP, Martine L, Raederstorff D, Grynberg A, Demaison L: Individual effects of dietary EPA and DHA on the functioning of the isolated working rat heart. Can J Physiol Pharmacol 76: 728–736, 1998

    Google Scholar 

  17. Neely JR, Leibermeister H, Battersby EJ, Morgan HE: Effect of pressure development on oxygen consumption by isolated rat hearts. Am J Physiol 212: 804–814, 1967

    Google Scholar 

  18. Palmer JW, Tandler B, Hoppel CL: Biochemical properties of subsarcolemmal and interfibrillar mitochondria isolated from cardiac muscle. J Biol Chem 252: 8731–8739, 1991

    Google Scholar 

  19. Demaison L, Moreau D, Martine L, Chaudron I, Grynberg A: Myocardial ischemia and in vitro mitochondrial metabolic efficiency. Mol Cell Biochem 158: 161–169, 1996

    Google Scholar 

  20. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Proteins measurement with the folin reagent. J Biol Chem 193: 265–275, 1951

    Google Scholar 

  21. Chance B, Williams GR: The polarographic measurement of mitochondrial respiration. Adv Enzymol 17: 5–34, 1956

    Google Scholar 

  22. Estabrook RW: Mitochondrial respiratory control and polarographic measurement of ADP:O ratios. In: R.W. Estabrook (ed). Methods in Enzymology, Vol. 10. Academic Press, New York, 1967, pp 41–47

    Google Scholar 

  23. Teerlink T, Hennekes M, Bussemaker J, Groeneveld J: Simultaneous determination of creatine compounds and adenine nucleotides in myocardial tissue by high-performance liquid chromatography. Anal Biochem 214: 278–283, 1993

    Google Scholar 

  24. Fabiato A, Fabiato F: Calculator programs for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. J Physiol Paris 75: 463–505, 1979

    Google Scholar 

  25. Demaison L, Grégoire S, Dubois F: A new mathematical model for the evaluation of oxidative phosphorylation in isolated cardiac mitochondria: Application to the effects of palmitoylcarnitine and free calcium concentrations. Exp Clin Cardiol 4: 137–146, 1999

    Google Scholar 

  26. Folch J, Lees M, Sloane-Stanley GH: A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226: 497–509, 1957

    Google Scholar 

  27. Juaneda P, Rocquelin G: Rapid and convenient separation of phospholipids and non phosphorus lipids from rat hearts using silica cartridge. Lipids 20: 40–41, 1985

    Google Scholar 

  28. Dagnélie P: Théories et Méthodes Statistiques. Presses Agronomiques de Gembloux, Gembloux, 1975

    Google Scholar 

  29. Kang JX, Leaf A: Evidence that free polyunsaturated fatty acids modify Na+ channels by directly binding to the channel proteins. Proc Natl Acad Sci USA 93: 3542–3546, 1996

    Google Scholar 

  30. Kang JX, Leaf A: The cardiac antiarrhythmic effects of polyunsaturated fatty acid. Lipids 31: S41–S44, 1996

    Google Scholar 

  31. Honore E, Barhanin J, Attali B, Lesage F, Lazdunski M: External blockade of the major cardiac delayed-rectifier K+ channel (Kv1.5) by polyunsaturated fatty acids. Proc Natl Acad Sci USA 91: 1937–1941, 1994

    Google Scholar 

  32. Xiao YF, Kang JX, Morgan JP, Leaf A: Blocking effects of polyunsaturated fatty acids on Na+ channels of neonatal rat ventricular myocytes. Proc Natl Acad Sci USA 92: 11000–11004, 1995

    Google Scholar 

  33. Xiao YF, Gomez AM, Morgan JP, Lederer WJ, Leaf A: Suppression of voltage-gated L-type Ca2+ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes. Proc Natl Acad Sci USA 94: 4182–4187, 1997

    Google Scholar 

  34. Bogdanov KY, Spurgeon HA, Vinogradova TM, Lakatta EG: Modulation of the transient outward current in adult rat ventricular myocytes by polyunsaturated fatty acids. Am J Physiol 274: H571–H579, 1998

    Google Scholar 

  35. Kang JX, Xiao YF, Leaf A: Free, long-chain, polyunsaturated fatty acids reduce membrane electrical excitability in neonatal rat cardiac myocytes. Proc Natl Acad Sci USA 92: 3997–4001, 1995

    Google Scholar 

  36. Leaf A, Kang JX, Xiao YF, Billman GE: Dietary n-3 fatty acids in the prevention of cardiac arrhythmias. Curr Opin Clin Nutr Metab Care 1: 225–228, 1998

    Google Scholar 

  37. Kang JX, Leaf A: Effects of long-chain polyunsaturated fatty acids on the contraction of neonatal rat cardiac myocytes. Proc Natl Acad Sci USA 91: 9886–9890, 1994

    Google Scholar 

  38. Lapidus RG, Sokolove PM: The mitochondrial permeability transition. Interactions of spermine, ADP, and inorganic phosphate. J Biol Chem 269: 18931–18936, 1994

    Google Scholar 

  39. Demaison L, Grynberg A: Cellular and mitochondrial energy metabolism in the stunned myocardium. Basic Res Cardiol 89: 293–307, 1994

    Google Scholar 

  40. Miyata H, Lakatta EG, Stern MD, Silverman HS: Relation of mitochondrial and cytosolic free calcium to cardiac myocyte recovery after exposure to anoxia. Circ Res 71: 605–613, 1992

    Google Scholar 

  41. Pepe S, Tsuchiya N, Lakatta EG, Hansford RG: Cardiac mitochondrial membrane n-3/n-6 polyunsaturated fatty acid ratio modulates pyruvate dehydrogenase activation. J Mol Cell Cardiol 30: A112, 1998

    Google Scholar 

  42. Borutaite V, Morkuniene R, Brown GC: Release of cytochrome c from heart mitochondria is induced by high Ca2+ and peroxynitrite and is responsible for Ca2+-induced inhibition of substrate oxidation. Biochim Biophys Acta 1453: 41–48, 1999

    Google Scholar 

  43. Pietri S, Culcasi M, Stella L, Cozzone PJ: Ascorbyl free radical as a reliable indicator of free radical-mediated myocardial ischemic and post-ischemic injury. A real-time continuous-flow ESR study. Eur J Biochem 193: 845–854, 1990

    Google Scholar 

  44. Buettner GR, Jurkiewicz BA: Ascorbate free radical as a marker of oxidative stress: An EPR study. Free Radic Biol Med 14: 49–55, 1993

    Google Scholar 

  45. Blasig IE, Shuter S, Garlick P, Slater T: Relative time-profile for free radical trapping, coronary flow, enzyme leakage, arrhythmias, and function during myocardial reperfusion. Free Radic Biol Med 16: 35–41, 1994

    Google Scholar 

  46. Kojda G, Harrison D: Interactions between NO and reactive oxygen species: Pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure. Cardiovasc Res 43: 562–571, 1999

    Google Scholar 

  47. Ross S: Atherosclerosis: An inflammatory disease. New Engl J Med 340:115–126. Can J Physiol Pharmacol 76:728-736, 1999

Download references

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Demaison, L., Moreau, D., Vergely-Vandriesse, C. et al. Effects of dietary polyunsaturated fatty acids and hepatic steatosis on the functioning of isolated working rat heart under normoxic conditions and during post-ischemic reperfusion. Mol Cell Biochem 224, 103–116 (2001). https://doi.org/10.1023/A:1011934603667

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