What is the Key Step in Muscle Fatty Acid Oxidation after Change of Plasma Free Fatty Acids Level in Rats?

  • Doh, Kyung-Oh (Department of Physiology, Yeungnam University College of Medicine) ;
  • Suh, Sang-Dug (Department of Physiology, Yeungnam University College of Medicine) ;
  • Kim, Jong-Yeon (Department of Physiology, Yeungnam University College of Medicine)
  • Published : 2005.06.21


The purpose of this study was to discern the critical point in skeletal muscle fatty acid oxidation by changing plasma free fatty acids (FFA) level in rat. In the study, 3 key steps in lipid oxidation were examined after changing plasma FFA level by acipimox. The rates of both palmitate and palmitoylcarnitine oxidation were decreased by decrease of plasma FFA level, however, carnitine palmitoyl transferase (CPT) 1 activity was not changed, suggesting CPT1 activity may not be involved in the fatty acid oxidation at the early phase of plasma FFA change. In the fasted rats, ${\beta}-hydroxy$ acyl-CoA dehydrogenase (${\beta}$-HAD) activity was depressed to a similar extent as palmitate oxidation by a decrease of plasma FFA level. This suggested that ${\beta}-oxidation$ might be an important process to regulate fatty acid oxidation at the early period of plasma FFA change. Citrate synthase activity was not altered by the change of plasma FFA level. In conclusion, the critical step in fatty acids oxidation of skeletal muscles by the change of plasma FFA level by acipimox in fasting rats might be the ${\beta}-oxidation$ step rather than CPT1 and TCA cycle pathways.


  1. Bulow J. Lipid mobilization and utilization. Principles of Exercise Biochemistry. 1st ed. Basel, Karger, p 140-163, 1988
  2. Dagenais GR, Tancredi RG, Zierlier KL. Free fatty acid oxidation by forearm muscle at rest, and evidence for an intramuscular lipid pool in human forearm. J Clin Invest 58: 421-431, 1976 https://doi.org/10.1172/JCI108486
  3. Gollnick PD, Saltin B. Significance of skeletal muscle oxidative enzyme enhancement with endurance training: hypothesis. Clin Physiol 2: 1-12, 1982 https://doi.org/10.1111/j.1475-097X.1982.tb00001.x
  4. Howald H, Hoppeler H, Claasen H, Mathieu O, Straub R. Influence of endurance training on the ultrastructural composition of the different muscle fiber types in humans. Pfluegers Arch 403: 369- 376, 1985 https://doi.org/10.1007/BF00589248
  5. Kim JY, Hickner RC, Dohm GL, Houmard JA. Long- and medium-chain fatty acid oxidation is increased in exercisetrained human skeletal muscle. Metabolism 51: 460-464, 2002a https://doi.org/10.1053/meta.2002.31326
  6. McGarry JD, Brown NF. The mitochndrial carnitine palmitoyltransferase system from concept to molecular analysis. Eur J Biochem 244: 1-14, 1997 https://doi.org/10.1111/j.1432-1033.1997.00001.x
  7. Watt MJ, Holmes AG, Steinberg GR, Mesa JL, Kemp BE, Febbraio MA. Reduced plasma FFA availability increases net triacylglycerol degradation, but not GPAT or HSL activity, in human skeletal muscle. Am J Physiol Endocrinol Metab 287: E120- E127, 2004 https://doi.org/10.1152/ajpendo.00542.2003
  8. Piatti PM, Monti LD, Davis SN, Conti M, Brown MD, Pozza G, Alberti KG. Effects of an acute decrease in non-esterified fatty acid levels on muscle glucose utilization and forearm indirect calorimetry in lean NIDDM patients. Diabetologia 39: 103-112, 1996
  9. Kim JY, Koves TR, Yu GS, Gulick T, Cortright RN, Dohm GL, Muoio DM. Evidence of a malonyl-CoA-insensitive carnitine palmitoyltransferase I activity in red skeletal muscle. Am J Physiol Endocrinol Metab 282: E1014-E1022, 2002b https://doi.org/10.1152/ajpendo.00233.2001
  10. Van der Vusse GJ, Reneman RS. Lipid metabolism in muscle. In: Rowell LB, Shepherd JT ed, Handbook of Physiology. 1st ed. Oxford University Press, New York, p 952-994, 1996
  11. Zierz S, Engel AG. Different sites of inhibition of carnitine palmitoyltransferase by malonyl-CoA, and by acetyl-CoA and CoA, in human skeletal muscle. Biochem J 245: 205-209, 1987 https://doi.org/10.1042/bj2450205
  12. Scholte HR, Yu Y, Ross JD, Oosterkamp II, Boonman AM, Busch HF. Rapid isolation of muscle and heart mitochondria, the lability of oxidative phosphorylation and attempts to stabilize the process in vitro by taurine, carnitine and other compounds. Mol Cell Biochem 174: 61-66, 1997 https://doi.org/10.1023/A:1006803807814
  13. Srele PA. Citrate synthase. Meth Enzymol 13: 3-26, 1969 https://doi.org/10.1016/0076-6879(69)13005-0
  14. Donati A, Cavallini G, Carresi C, Gori Z, Parentini I, Bergamini E. Anti-aging effects of anti-lipolytic drugs. Exp Gerontol 39: 1061-1067, 2004 https://doi.org/10.1016/j.exger.2004.03.025
  15. McGarry JD, Mills SE, Long CS, Foster DW. Observations on the affinity for carnitine, and malonyl-CoA sensitivity, of carnitine palmitoyltransferase I in animal and human tissues. Demonstration of the presence of malonyl-CoA in non-hepatic tissues of the rat. Biochem J 214: 21-28, 1983 https://doi.org/10.1042/bj2140021
  16. Tornvall P, Walldius GW. A comparison between nicotinic acid and acipimox in hypertriglyceridaemia--effects on serum lipids, lipoproteins, glucose tolerance and tolerability. J Intern Med 230: 415-421, 1991 https://doi.org/10.1111/j.1365-2796.1991.tb00466.x
  17. Kim JY, Hickner RC, Cortright RL, Dohm GL, Houmard JA. Lipid oxidation is reduced in obese human skeletal muscle. Am J Physiol Endocrinol Metab 279: E1039-E1044, 2000 https://doi.org/10.1152/ajpendo.2000.279.5.E1039
  18. Randle PJ. Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab Rev 14: 263-283, 1998 https://doi.org/10.1002/(SICI)1099-0895(199812)14:4<263::AID-DMR233>3.0.CO;2-C