Abstract
Dietary restriction increases life span and delays the development of age-related diseases in rodents. We have recently demonstrated that chronic dietary restriction is beneficial on recovery of heart function following ischemia. We studied whether the metabolic basis of this benefit is associated with alterations in mitochondrial respiration. Male Wistar rats were assigned to an ad libitum-fed (AL) group and a food restricted (FR) group, in which food intake was reduced to 55% of the amount consumed by the AL group. Following an 8-month period of restricted caloric intake, isolated working hearts perfused with glucose and high levels of fatty acids were subjected to global ischemia followed by reperfusion. At the end of reperfusion, total heart mitochondria was respiration was assessed in the presence of pyruvate, tricarboxylic acid intermediates, and palmitoylcarnitine. Recovery of heart function following ischemia was greater in FR hearts compared to AL hearts. Paralleling these changes in heart function was in increase in state 3 respiration with pyruvate. The respiratory control ratios in the presence of pyruvate and tricarboxylic acid intermediates were higher in FR hearts compared to AL hearts, indicating well-coupled mitochondria. Overall energy production, expressed as the ADP:O ratio and the oxidative phosphorylation rate, was also improved in FR hearts. Our results indicate that the beneficial effect of FR on recovery of heart function following ischemia is associated with changes in mitochondrial respiration.
Similar content being viewed by others
References
Yu BP, Masoro EJ, Murata I, Bertrand HA, Lynd FT: Life span study of the SPF Fischer 344 male rats fed ad libitum or restricted diets: Longevity, growth, lean body mass and disease. J Gerontol 37: 130–141, 1982
Masoro E: Antiaging action of caloric restriction: Endocrine and metabolic aspects. Obes Res 3(suppl 1): 241–247, 1995
Sohal RS, Weindruch R: Oxidative stress, caloric restriction, and aging. Science 273: 59–63, 1996
Klebanov S, Herlihy JT, Freeman GR: Effect of long-term food restriction on cardiac mechanics. Am J Physiol 273: H2333–H2342, 1997
Kelley GR, Herlihy JT: Food restriction alters the age-related decline in cardiac beta-adrenergic responsiveness. Mech Ageing Dev 103: 1–12, 1988
Broderick TL, Driedzic WR, Gillis M, Jacob J, Belke T: Effects of chronic food restriction and exercise training on recovery of cardiac function following ischemia. J Gerontol Biol Sci 56: B1–B5, 2001
Kim SW, Yu BP, Sanderford M, Herlihy JT: Dietary restriction modulates the norepinephrine content and uptake of the heart. Proc Soc Exp Biol Med 207: 43–47, 1994
Wetter TJ, Gazdag AC, Dean DJ, Cartee GD: Effect of calorie restriction on in vivo metabolism by individual tissues in rats. Am J Physiol 276: E728–E738, 1999
Papa PC, Seraphim PR, Machado UF: Loss of weight restores GLUT 4 content in insulin-sensitive tissues of monosodium glutamatetreated obese mice. Int J Obes Relat Metab Disord 21: 1065–1070, 1994
Bunger R, Mallet RT, Hartman DA: Pyruvate-enhanced phosphorylation potential and inotropism in normoxic and postischemic isolated working heart. Eur J Biochem 180: 231–233, 1989
Neely JR, Whitmer M, Mochizuki S: Effects of mechanical activity and hormones on myocardial glucose and fatty acid utilization. Circ Res 38: I22–I30, 1976
Svensson S, Svedjeholm R, Ekroth R, Milocco I, Nilsson F, Dabel KG, William-Olsson G: Trauma metabolism in the heart: Uptake of substrates and the effects of insulin early after cardiac operations. J Thorac Cardiovasc Surg 99: 1063–1073, 1990
Paulson DJ, Shug AL: Inhibition of the adenine nucleotide translocator by matrix-localized palmitoyl-CoA in rat heart mitochondria. Biochem Biophys Acta 766: 70–76, 1984
Edoute Y, Kotze JCN, Lochne A: Oxidative phosphorylation rate: An index for evaluation of mitochondrial function in myocardial ischemia. J Mol Cell Cardiol 11: 831–833, 1979
Arnall DA, Palmer WK, Miller WC, Oscai LB: Effect of fasting on myocardial substrates in male and female rats. Am J Physiol 254: C560–C563, 1988
Lewandowski ED, White LT: Pyruvate dehydrogenase influences on postischemic heart function. Circulation 91: 2071–2079, 1985
McVeigh JJ, Lopaschuk GD: Dichloroacetate stimulation of glucose oxidation improves recovery of ischemic rat hearts. Am J Physiol 259: H1070–H1085, 1990
Lopaschuk GD: Alterations in fatty acid oxidation during reperfusion of the heart after myocardial ischemia. Am J Cardiol 80: 11A–16A, 1997
Vanoverschelde JLJ, Janier MF, Bakke JE, Marshall DR, Bergmann SR: Rate of glycolysis during ischemia determines the extent of ischemic injury and functional recovery after reperfusion. Am J Physiol 267: H1785–H1794, 1994
Kirsch A, Savabi F: Effect of food restriction in the phosphocreatine energy shuttle components in rat heart. J Mol Cell Cardiol 24: 821–830, 1992
Daneshrad Z, Novel-Chate V, Birot O, Serrurier B, Sanchez H, Bigard AX, Rossi A: Diet restriction plays an important role in the alterations of heart mitochondria following exposure of young rats to chronic exposure. Eur J Physiol 442: 12–18, 2001
Savabi F, Kirsch A: Diabetic type of cardiomyopathy in food-restricted rats. Can J Physiol Pharmacol 70: 1040–1047, 1992
Xia E, Rao G, Van Remmen H, Heydari AR, Richardson A: Activities of antioxidant enzymes in various tissues of male Fischer 344 rat are altered by food restriction. J Nutr 125: 195–201, 1995
Sohal RS, Ku HH, Agarwal S, Forster MJ, Lal H: Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse. Mech Ageing Dev 74: 121–133, 1994
Lass A, Sohal BH, Weindruch R, Forster MJ, Sohal RS: Caloric restriction prevents age-associated accrual of oxidative damage to mouse skeletal muscle mitochondria. Free Radic Biol Med 25: 1089–1097, 1988
Bolli R, Patel BS, Jeroudi MO, Lai EK, McCay PB: Demonstration of free radical generation in ‘stunned’ myocardium of intact dogs with the use of the spin trap alpha-phenyl N-tert-butyl nitrone. J Clin Invest 82: 476–485, 1988
Broderick TL, Driedzic WR, Paulson DJ: Propionyl-L-carnitine effects on postischemic recovery of mechanical function and substrate oxidation in the diabetic heart. Mol Cell Biochem 206: 151–157, 2000
McCormack JG, Barr RL, Wolff AA, Lopaschuk GD: Ranolazine stimulates glucose oxidation in normoxic, ischemic, and reperfused ischemic hearts. Circulation 93: 135–142, 1996
Palmer JW, Tandler B, Hoppel CL: Biochemical properties of subsarcolemmal and interfibrillar mitochondria isolated from rat cardiac muscle. J Biol Chem 252: 8731–8739, 1977
Hoppel CL, Tandler B, Parland W, Turkaly JS, Albers LD: Hamster cardiomyopathy: A defect in oxidative phosphorylation in cardiac interfibrillar mitochondria. J Biol Chem 257: 1540–1548, 1982
Lesnefsky EJ, Ramani K, Fannin S, Slabe TJ, Hoppel CL: Aging selectively decreases oxidative capacity in interfibrillar rat mitochondria. Circulation 90: I209, 1994
Ueta H, Ogura M, Sugiyama A, Kagiyama A, Shin G: Spin trapping of cardiac submitochondrial particles isolated from ischemic and nonischemic myocardium. J Mol Cell Cardiol 22: 893–899, 1990
Rights and permissions
About this article
Cite this article
Broderick, T.L., Belke, T. & Driedzic, W.R. Effects of chronic caloric restriction on mitochondrial respiration in the ischemic reperfused rat heart. Mol Cell Biochem 233, 119–125 (2002). https://doi.org/10.1023/A:1015506327849
Issue Date:
DOI: https://doi.org/10.1023/A:1015506327849