Journal of Community Nutrition

The Korean Society of Community Nutrition (대한지역사회영양학회)
권호 표지

Effects of Exercise and Supplementation of L-Carnitine and Antioxidants on Mitochondrial Function in Rats

  • Kim, Sook-Bae (Department of Food Science and Human Nutrition, Chonbuk National University) ;
  • Kim, Sun-Ju (Department of Food Science and Human Nutrition, Chonbuk National University)
  • Published : 2002.11.01
Download PDF
⟨ Previous Next ⟩

Abstract

This study was investigated the effects of exercise and supplementation of L-carnitine and antioxidants on hepatic mitochondrial function, especially oxidative phosphorylation (OXPHOS). Isolated hepatic mitochondria from 4 rat groups were functionally tested by an analysis of respiration and the coupling of this process to ATP synthesis in the presence of ADP. Four groups were non-trained, non-supplemented group (NTNS), non-trained, supplemented group (NTS), long term-trained, non-supplemented group (LTNS) , and long term-trained, supplemented group (LTS). The trained rats run on a treadmill (grade 10°,20 m/min) for 60min/day for 8 weeks. The supplemented rats were treated with L-carnitine (0.5% diet), vitamin E(0.5mg/g BW), vitamin C (0.5mg/g BW) and melatonin (1 $\mu$ g/g BW) for 8 weeks. There were exercise effects on improving mitochondrial OXPHOS. Within non-supplemented groups, exercised rats resulted in a significant decrease in state 4 oxygen consumption, which increased the respiratory control (RC) ratio and ADP : O (P/O) ratio. There were supplementation effects on improving mitochondrial OXPHOS, too. Within non-exercised rats, supplemented rats resulted in a significant decrease in state 4 oxygon consumption. which increased the RC ratio and P/O ratio. There were additive effects of exercise and supplementation on OXPHOS. Within supplemented rats, exercise resulted in an increase in RC ratio. Significant effects of exercise-supplement interaction on improving OXPHOS were identified. It suggests that exercise and supplementation of L-carnitine and antioxidants might improve more efficiently the impaired OXPHOS efficiency in mitochondrial dysfunction that recognized as is an important cause of degenerative diseases. (J Community Nutrition 4(3) : 187∼194, 2002)

Keywords

References

  1. Ahmad S, Robertson T, Golper TA(1990) : Multicenter trial of Lcarnitine in maintenance hemodialysis patients : clinical biochemical effects. Kidney lnt 38 : 912-918 https://doi.org/10.1038/ki.1990.290
  2. Arenas J, Huertas R, Campos Y, Diaz AE, Evillalon JM, Vilas E (1994) : Effectsof L-carnitine on the pyruvate dehydrogenase complex and carnitine palmitoyl transferase activities in muscle of endurance athletes. FEBS Letters 341 : 91-93 https://doi.org/10.1016/0014-5793(94)80246-7
  3. Baskin CR, Hinchcliff KW, Disilvestro RA, Reinhart GA, Hayek MG, Chew BP, Burr JR, Swenson RA(2000) : Effectof dietary antioxidant supplementation on oxidative damage and resistance to oxidative damage during prolonged exercise in sleddogs. Am J Ver Res 61(8) : 886-891 https://doi.org/10.2460/ajvr.2000.61.886
  4. Bejma J, Ramires P, Ji LL(2000) : Free radical generation and oxidative stress with ageing and exercise : differential effects in the myocardium and liver. Acta Physiol Scand 169 (4) : 343-351 https://doi.org/10.1046/j.1365-201x.2000.00745.x
  5. Berthon P, Freyssenet D, Chatard JC, Castelles J, Mujika I, Geyssant A, Guezennec CY, Denis C (1995) : Mitochondrial ATP production rate in 55 to 73-year-old men : effect of endurance training. Acta Physiol Scand 154 : 269-274 https://doi.org/10.1111/j.1748-1716.1995.tb09908.x
  6. Bieber LL (1988) : Carnitine. Annu Rev BioChem 57 : 261-283 https://doi.org/10.1146/annurev.bi.57.070188.001401
  7. Brass EP, Hiatt WR (1994) : Camitine metabolism during exercise. Life Science 54(9) : 1383-1393 https://doi.org/10.1016/0024-3205(94)00593-1
  8. Brass EP, Hiatt WR (1998) : The role of camitine and carnitine supplementation during exercise in man and in individuals with special needs. J Am Coll Nutr 17 (3) : 207-215 https://doi.org/10.1080/07315724.1998.10718750
  9. Brown MD, Wallace DC(1994) : Molecular basis of mitochondrial DNA disease. J Bioenerg Biomembr 26 : 273-289 https://doi.org/10.1007/BF00763099
  10. Buttgereit F, Brand MD(1995) : A hierarchy of ATP-consuming processes in mammalian cells. Biochem J 312 : 163-167 https://doi.org/10.1042/bj3120163
  11. Chance B, Williams GR(1955) : Respiratory enzymes in oxidative phosphorylation. J Biol Chem 217 : 409-427
  12. Chen J, Gollnick PD(1994) : Effect of exercise on hexokinase distribution and mitochondrial respiration in skeletal muscle. Pflugers Arch 427 : 257-263 https://doi.org/10.1007/BF00374532
  13. Clarkson PM (1995) : Antioxidants and physical performance. Crit Rev Food Sci Nutr 35 : 131-141 https://doi.org/10.1080/10408399509527692
  14. Corral-Debrinski M, Stepien G, Shoffner JM, Lott MT, Kanter K, Wallace DC(1991) : Hypoxemia is associated with mitochondrial DNA damage and gene induction implications for cardiac disease. JAMA 266 (13) : 1739-1740 https://doi.org/10.1001/jama.266.13.1739
  15. Estabrook RW(1967) : Mitochondrial respiratory control and the polarographic measurement of ADP : O ratios. In : Estabrook RW, Pullaman ME eds. Methods in enzymology 10, ppAI-47, Academic press, New York and London
  16. Hagen TM, Uowe DL, Bartholomew J(1997) : Mitochondrial decay in hepatocytes from old rats : membrane potential declines, heterogeneity and oxidants increase. Proc Natl Acad Sci USA 94 : 3064-3069 https://doi.org/10.1073/pnas.94.7.3064
  17. Holt IJ, Harding AE(1988) : Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331 : 717-719 https://doi.org/10.1038/331717a0
  18. Huertas R, Campos Y, Diaz E, Esteban J, Vechietti L, Montanari G, Montanari G, D'Iddio S, Corsi M, Arenas J(1992) : Respiratory chain enzymes in muscle of endurance athletes. Effect of L-camitine Biochim Biophys Res Commun 188(1) : 102-107 https://doi.org/10.1016/0006-291X(92)92355-2
  19. Infante JP, Huszagh VA(2000) : Secondary camitine deficiency and impaired docosahexaenoic acid synthesis : a common denominator in the patho-physiology of diseases of OXPHOS and $\beta$-oxidation. FEBS Letters 468 : 1-5 https://doi.org/10.1016/S0014-5793(00)01083-8
  20. Johnson D, Lardy H(1967) : Isolation of liver or kidney mitochondria. In : Estabrook RW, Pullaman ME eds. Methods in enzymology 10, pp.94-96, Academic press, New York and London
  21. Kim MC, Berdanier CD(1998) : Nutrient-gene interactions determine mitochondrial function : effect of dietary fat. FASEB J 12 : 243-248 https://doi.org/10.1096/fasebj.12.2.243
  22. Lancha AH, Recco MB, Abdalla DS, Curi R(1995) : Effect of aspartate, asparagine, and carnitine supplementation in the diet on metabolism of skeletal muscle during a moderate exercise. Physiol Behav 57 (2) : 367-371 https://doi.org/10.1016/0031-9384(94)00243-X
  23. Larsson NG, Luft R (1999) : Revolution in mitochondrial medicine. FEBS Letters 455 : 199-202 https://doi.org/10.1016/S0014-5793(99)00854-6
  24. Leeuwenburgh C, Heinecke JW (2001) : Oxidative stress and antioxidants in exercise. Curr Med Chem 8 (7) : 829-838 https://doi.org/10.2174/0929867013372896
  25. Matschinsky FA (1996) : A lesson in metabolic regulation inspired by the glucokinase glucose sensor paradigm. Diabetes 45 : 223-241 https://doi.org/10.2337/diabetes.45.2.223
  26. Mollica MP(2001) : Acetyl-L-carnitine treatment stimulates oxygen consumption and biosynthetic function in perfused liver of young and old rats. Cell Mol Life Sci 58 : 477-484 https://doi.org/10.1007/PL00000871
  27. Nicot C, Hegardt FG, Woldegiorgis G, Haro D, Marrero PF(2001) : Pig liver carnitine palmitoyltransferase I, with low Krn for carnitine and high sensitivity to malonyl-CoA inhibition, is a natural chimera of rat liver and muscle enzymes. Biochemistry 40(7) : 2260-2266 https://doi.org/10.1021/bi0024106
  28. Paradies G, Ruggiero FM, Gadaleta MN, Quagliariello E(1992) : The effect of aging and acetyl-L-carnitine on the activity of the phosphate carrier and on the phospholipid composition in rat heart mitochondria. Biochem Biophys Acta 1103(2) : 324-326 https://doi.org/10.1016/0005-2736(92)90103-S
  29. Pincemail J, Deby C, Pirmay F(1988) : Tocopherol mobilization during intensive exercise. Eur J Appl Physiol 57 : 189-191 https://doi.org/10.1007/BF00640661
  30. Reynafarje B, Costa LE, Lehninge, AL (1985) : $O_{2}$ solubility in aqueous media determined by a kinetic method. Analy Biochem 145 : 406-410 https://doi.org/10.1016/0003-2697(85)90381-1
  31. Robertson JD, Maughan RJ, Duthie GG(1991) : Increased blood antioxidant systems of runners in response to training load. Clin Sci 80 (6) : 611-618 https://doi.org/10.1042/cs0800611
  32. Sahlin K (1990) : Muscle carnitine metabolism during incremental dynamic exercise in humans. Acta Physiol Scand 138 (3) 259-262 https://doi.org/10.1111/j.1748-1716.1990.tb08845.x
  33. Schroder H, Navarro E, Tramullas A, Mora J, Galiano D (2000) : Nutrition anti oxidant status and oxidative stress in professional basketball players : Effects of a three compound antioxidative supplement. Int J sports Med 21 (2) : 146-150 https://doi.org/10.1055/s-2000-8870
  34. Sipliprand N (1985) : Carnitine and its role in metabolism. Acta Med Rom 23 : 237-250
  35. Starrit EC, Angus D, Hargreaves M (1999) : Effect of short-term training on mitochondrial ATP production rate in human skeletal muscle. J Appl Physiol 86 (2) : 450-454 https://doi.org/10.1152/jappl.1999.86.2.450
  36. Terblanche SE, Gohill K, Packer L, Henderson S, Brooks GA(2001) : The effects of endurance training and exhaustive exercise on mitochondrial enzymes in tissues of the rat. Comp Biochem Physiol 128 : 889-896 https://doi.org/10.1016/S1095-6433(00)00344-5
  37. Trounce I, Neill S, Wallace DC(1994) : Cytoplasmic transfer of the mtDNA 8993 T \longrightarrow G(ATP 6) point mutation associated with Leigh syndrome into mtDNA-less cells demonstrates cosegregation with a decrease in state III respiration and ADP/O ratio. Genetics 91 : 8334- 8338
  38. Venditti P, Masullo P, Meo SD(1999) : Effect of exercise duration on characteristics of mitochondrial population from rat liver. Arch Biochem Biophys 368 (1) : 112-120 https://doi.org/10.1006/abbi.1999.1269
  39. Villa RF, Turpeenoja L, Benzi G, Giuffrida Stella AM (1988) : Action of L-acetylcarnitine on age-dependent modifications of mitochondrial membrane proteins from rat cerebellum. Neuro chem Res 13(10) : 909-916 https://doi.org/10.1007/BF00970761
  40. Wallace DC (1992) : Mitochondrial genetics: A paradigm for aging and degenerative diseases? Science 256 : 628-632 https://doi.org/10.1126/science.1533953
  41. Wallace DC (1994) : Mitochondrial mutations in diseases of energy metabolism. J Bioenerg Biomembr 26 : 241-250 https://doi.org/10.1007/BF00763096
  42. Wallace DC, Shoffner JM, Trounce I, Brown MD, Ballinger SW(1995) : Mitochondrial DNA mutations in human degenerative diseases in aging. Biochim Biophy Acta 1271 : 141-151 https://doi.org/10.1016/0925-4439(95)00021-U
  43. Yoon GA(1999) : Antioxidant levels and lipid peroxidation in plasma and erythrocyte following treadmill running. Kor Nutr Soc 32 (8) : 870 -876