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Skeletal muscle substrate metabolism during exercise: methodological considerations

Published online by Cambridge University Press:  12 June 2007

Gerrit van Hall ,
José González-Alonso ,
Massimo Sacchetti  and
Bengt Saltin
Gerrit van Hall
Affiliation:
The Copenhagen Muscle Research Centre, Rigshospitalet, section 7652, Tagensvej 20, DK-2200 Copenhagen N, Denmark
José González-Alonso
Affiliation:
The Copenhagen Muscle Research Centre, Rigshospitalet, section 7652, Tagensvej 20, DK-2200 Copenhagen N, Denmark
Bengt Saltin*
Affiliation:
The Copenhagen Muscle Research Centre, Rigshospitalet, section 7652, Tagensvej 20, DK-2200 Copenhagen N, Denmark
*
*Corresponding Author: Dr Bengt Saltin, fax +45 3545 7634, email [email protected]
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Abstract

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The aim of the present article is to evaluate critically the various methods employed in studies designed to quantify precisely skeletal muscle substrate utilization during exercise. In general, the pattern of substrate utilization during exercise can be described well from O2 uptake measurements and the respiratory exchange ratio. However, if the aim is to quantify limb or muscle metabolism, invasive measurements have to be carried out, such as the determination of blood flow, arterio-venous (a-v) difference measurements for O2 and relevant substrates, and biopsies of the active muscle. As many substrates and metabolites may be both taken up and released by muscle at rest and during exercise, isotopes can be used to determine uptake and/or release and also fractional uptake can be accounted for. Furthermore, the use of isotopes opens up further possibilities for the estimation of oxidation rates of various substrates. There are several methodological concerns to be aware of when studying the metabolic response to exercise in human subjects. These concerns include: (1) the muscle mass involved in the exercise is largely unknown (bicycle or treadmill). Moreover, whether the muscle sample obtained from a limb muscle and the substrate and metabolite concentrations are representative can be a problem; (2) the placement of the venous catheter can be critical, and it should be secured so that the blood sample represents blood from the active muscle with a minimum of contamination from other muscles and tissues; (3) the use of net limb glycerol release to estimate lipolysis is probably not valid (triacylglycerol utilization by muscle), since glycerol can be metabolized in skeletal muscle; (4) the precision of blood-borne substrate concentrations during exercise measured by a-v difference is hampered since they become very small due to the high blood flow. Recommendations are given in order to obtain more quantitative and conclusive data in studies investigating the regulatory mechanisms for substrate choice by muscle.

Keywords

Free fatty acidsTriacylglycerolsExerciseMetabolic rateRespiratory exchange ratio
Type
Meeting Report
Information
Proceedings of the Nutrition Society , Volume 58 , Issue 4 , November 1999 , pp. 899 - 912
Copyright
The Nutrition Society

References

Ahlborg, G & Felig, F (1982) Lactate and glucose exchange across the forearm, legs and splanchnic bed during and after prolonged leg exercise. Journal of Clinical Investigation 69, 45–54.CrossRefGoogle ScholarPubMed
Ahlborg, G, Felig, P, Hagenfeldt, L, Hendler, R & Wahren, J (1974) Substrate turnover during prolonged exercise in man. Splanchnic and leg metabolism of glucose, free fatty acids, and amino acids. Journal of Clinical Investigation 53, 1080–1090.CrossRefGoogle ScholarPubMed
Ahlborg, G & Juhlin-Dannfelt, (1994) Effect of b-receptor blockade on splanchnic and muscle metabolism during prolonged exercise in man. Journal of Applied Physiology 76, 1037–1042.CrossRefGoogle Scholar
Andersen, P, Adams, RP, Sjøgaard, G, Thorboe, A & Saltin, B (1985) Dynamic knee extension as a model for study of isolated exercising muscle in humans. Journal of Applied Physiology 59, 1647–1653.CrossRefGoogle Scholar
Andersen, P & Saltin, B (1985) Maximal perfusion of skeletal muscle in man. Journal of Physiology 366, 233–249.CrossRefGoogle ScholarPubMed
Atwater, WO & Benedict, FG (1903) Experiments on the Metabolism of Matter and Energy in the Human Body. Agricultural Bulletin no. 136.Washington, DC: US Department of Agriculture.Google Scholar
Bang, O (1936) The lactate content of blood during and after muscular exercise in man. Skandinavische Archiv der Physiologie 74, 51–82.CrossRefGoogle Scholar
Benedict, FG & Carpenter, TM (1910) The Metabolism and Energy Transformations of Healthy Man During Rest, pp. 182–193. Washington, DC: The Carnegie Institute. .Google Scholar
Bergman, BC, Butterfield, GE, Wolfel, EE, Casazza, GA, Lopaschuk, GD & Brooks, GA (1999) Evaluation of exercise and training on muscle lipid metabolism. American Journal of Physiology 276, E106–E117.Google ScholarPubMed
Bergström, J (1962) Muscle electrolytes in man. Determination by neutron activation analysis on needle biopsy specimens. A study on normal subjects, kidney patients, and patients with chronic diarrhoea. Scandinavian Journal of Clinical and Laboratory Investigation Suppl. 68, 7–110.Google Scholar
Bergström, J, Hultman, E, Jorfeldt, L, Pernow, B & Wahren, J (1969) Effect of nicotinic acid on physical capacity and on metabolism of muscle glycogen in man. Journal of Applied Physiology 26, 170–176.CrossRefGoogle ScholarPubMed
Boesch, C, Décombaz, J, Slotboom, J & Kreis, R (1999) Observation of intramyocellular lipids by means of 1H magnetic resonance spectroscopy. Proceedings of the Nutrition Society 58, 841–850.CrossRefGoogle ScholarPubMed
Böje, O (1936) Der blutzucker während und nach körperlicher arbeit;(Maintenance of blood sugar before and after manual work). Skandinavische Archiv der Physiologie 74, Suppl. 10, 1–48.CrossRefGoogle Scholar
Christensen, E-H (1932) Der stoffwechsel und die respiratorischen funktionen bei schwerer körperliche arbeit (Metabolism and respiratory function during heavy manual work). Arbeitsphysiologie 5, 463–478.Google Scholar
Dagenais, GR, Tancredi, RG & Zierler, KL (1976) Free fatty acid oxidation by forearm muscle at rest, and evidence for an intramuscular lipid pool in the human forearm. Journal of Clinical Investigation 58, 421–431.CrossRefGoogle ScholarPubMed
Dill, DB, Edwards, HT & Talbott, JH (1932) Studies in muscular activity. VII. Factors limiting the capacity for work. Journal of Physiology 77, 49–62.CrossRefGoogle ScholarPubMed
Douglas, AR, Jones, NL & Reed, JW (1988) Calculation of whole blood CO2 content. Journal of Applied Physiology 65, 473–477.CrossRefGoogle ScholarPubMed
Elia, M, Khan, K, Calder, G & Kurpad, A (1993) Glycerol exchange across the human forearm assessed by a combination of tracer and arteriovenous exchange techniques. Clinical Science 84, 99–104.CrossRefGoogle ScholarPubMed
Essén, B, Hagenfeldt, L & Kaijser, L (1977) Utilization of blood-borne and intramuscular substrates during continuous and intermittent exercise in man. Journal of Physiology 265, 489–506.CrossRefGoogle ScholarPubMed
Fridén, J, Seger, J & Ekblom, B (1989) Topographical localization of muscle glycogen: an ultrahistochemical study in the human vastus lateralis. Acta Physiologica Scandinavica 135, 381–391.CrossRefGoogle ScholarPubMed
Fröberg, SO, Carlson, LA & Ekelund, L-G (1971) Local lipid stores and exercise. In Muscle Metabolism During Exercise. Advances in Experimental Medicine and Biology, Vol. 11, pp. 307–313 [Pernow, B and Saltin, B, editors.] New York: Plenum Press.CrossRefGoogle Scholar
Fröberg, SO & Mossfeldt, F (1971) Effect of prolonged strenuous exercise on the concentration of triglycerides, phospholipids and glycogen in muscle of man. Acta Physiologica Scandinavica 82, 167–171.CrossRefGoogle ScholarPubMed
Gollnick, PD, Karlsson, J, Piehl, K & Saltin, B (1974) Selective glycogen depletion in skeletal muscle fibres of man following sustained contractions. Journal of Physiology 241, 59–67.CrossRefGoogle ScholarPubMed
Gollnick, PD, Pernow, B, Essén, B, Janson, E & Saltin, B (1981) Availability of glycogen and plasma FFA for substrate utilization in leg muscle of man. Clinical Physiology 1, 12–42.CrossRefGoogle Scholar
González-Alonso, J, Calbert, JAL & Nielsen, B (1998) Muscle blood flow is reduced with dehydration during prolonged exercise in humans. Journal of Physiology 513, 895–905.CrossRefGoogle ScholarPubMed
González-Alonso, J, Calbert, JAL & Nielsen, B (1999) Metabolic and thermodynamic responses to dehydration induced reductions in muscle blood flow in exercising humans. Journal of Physiology 520, 577–589.CrossRefGoogle ScholarPubMed
Hagenfeldt, L (1975) Turnover of individual free fatty acids in man. Federation Proceedings 34, 2246–2249.Google ScholarPubMed
Hagenfeldt, L, Hellström, K & Wahren, J (1975) Triglyceride, free fatty acid and carbohydrate metabolism in hyperlipaemic (type IV) and normlipaemic subjects on carbohydrate- or fat-rich diets. Clinical Science and Molecular Medicine 48, 247–257.Google ScholarPubMed
Hagenfeldt, L & Wahren, J (1968) Human forearm muscle metabolism during exercise II. Uptake, release and oxidation of individual FFA and glycerol. Scandinavian Journal of Clinical and Laboratory Investigation 21, 263–276.CrossRefGoogle ScholarPubMed
Hagenfeldt, L & Wahren, J (1972) Human forearm muscle metabolism during exercise. VII. FFA uptake and oxidation at different work intensities. Scandinavian Journal of Clinical and Laboratory Investigation 30, 429–436.CrossRefGoogle ScholarPubMed
Hargreaves, M (1995) Exercise Metabolism. Champaign, IL: Human Kinetics.Google Scholar
Hargreaves, M, Kiens, B & Richter, E (1991) Effect of increased plasma free fatty concentrations on muscle metabolism in exercise in exercising men. Journal of Applied Physiology 70, 194–201.CrossRefGoogle ScholarPubMed
Harms, CA, Babcock, MA, McClaran, SR, Pegelow, DF, Nickele, GA, Nelson, WB & Dempsey, JA (1997) Respiratory muscle work compromises leg blood flow during maximal exercise. Journal of Applied Physiology 82, 1573–1583.CrossRefGoogle ScholarPubMed
Havel, RJ, Carlson, LA, Ekelund, L-G & Holmgren, A (1964) Turnover rate and oxidation of different free fatty acids in man during exercise. Journal of Applied Physiology 19, 613–618.CrossRefGoogle ScholarPubMed
Havel, RJ, Pernow, B & Jones, NL (1967) Uptake and release of free fatty acids and other metabolites in the legs of exercising men. Journal of Applied Physiology 23, 90–99.CrossRefGoogle ScholarPubMed
Henriksson, J (1977) Training induced adaptations of skeletal muscle and metabolism during submaximal exercise. Journal of Physiology 270, 661–675.CrossRefGoogle ScholarPubMed
Hermansen, L, Hultman, E & Saltin, B (1967) Muscle glycogen during prolonged severe exercise. Acta Physiologica Scandinavica 71, 129–139.CrossRefGoogle ScholarPubMed
Horton, ES & Terjung, RL (editors) (1988) Exercise Nutrition and Energy Metabolism. New York: Macmillan Publishing Co.Google Scholar
Hurley, BF, Nemeth, PM, Martin WH., III, Hagberg, JM, Dalsky, GP & Hollozy, JO (1986) Muscle triglyceride utilisation during exercise: effect of training. Journal of Applied Physiology 60, 562–567.CrossRefGoogle ScholarPubMed
Jansson, E & Kaijser, L (1982) Effect of diet on the utilization of blood-borne and intramuscular substrates during exercise in man. Acta Physiologica Scandinavica 115, 19–30.CrossRefGoogle ScholarPubMed
Jorfeldt, L & Wahren, J (1971) Leg blood flow during exercise in man. Clinical Science 41, 459–473. .CrossRefGoogle ScholarPubMed
Kiens, B, Éssén-Gustavsson, B, Christensen, NJ & Saltin, B (1993) Skeletal muscle substrate utilisation during submaximal exercise in man: effect of endurance training. Journal of Physiology 469, 459–478.CrossRefGoogle ScholarPubMed
Kiens, B & Richter, EA (1998) Utilization of skeletal muscle triacylglycerol during post exercise recovery in humans. American Journal of Physiology 275, E332–E337.Google Scholar
Kim, CK, Strange, S, Bangsbo, J & Saltin, B (1995) Skeletal muscle perfusion in electrically induced dynamic exercise in humans. Acta Physiologica Scandinavica 153, 279–287.CrossRefGoogle ScholarPubMed
Krogh, A & Lindhard, J (1920) The relative value of fat and carbohydrate as sources of muscular energy. Biochemical Journal 14, 290–336.CrossRefGoogle ScholarPubMed
Kryger, AI (1998) Effects of Resistance Training on Skeletal Muscle and Function in the Oldest Old. PhD Thesis, University of Copenhagen.Google Scholar
Lavoisier, AL(1777) Mémoire sur la combustion en général, pp. 592–600.Mémoire de l'Académie Royale des Sciences.Google Scholar
Mittendorfer, B, Sidossis, LS, Walser, E, Chinkes, DL & Wolfe, RR (1998) Regional acetate kinetics and oxidation in human volunteers. American Journal of Physiology 274, E978–E983.Google ScholarPubMed
Narici, MV, Hoppeler, H, Kayser, B, Landoni, L, Claassen, H, Gavardi, C, Conti, M & Cerretelli, P (1996) Human quadriceps cross-sectional area, torque and neural activation during 6 months strength training. Acta Physiologica Scandinavica 157, 175–186.CrossRefGoogle ScholarPubMed
Narici, MV, Roi, GS, Landoni, L, Minetti, AE & Cerretelli, P (1989) Changes in force, cross-sectional area and neural activation during strength training and detraining of the human quadriceps. European Journal of Applied Physiology 59, 310–319.CrossRefGoogle ScholarPubMed
Needham, D (1971) Machina Carnis. London: Cambridge University Press.CrossRefGoogle Scholar
Obenholzer, F, Claassen, H, Moesch, H & Howald, H (1976) Ultrastrukturelle, biochemische und energetische analyse einer extremer dauerleistung (100 km lauf) (Microstructural, biochemical and energetic analysis of extreme continuous exercise (100 km run)). Schweizer Zeitschrift der Sportmedicin 24, 71–98.Google Scholar
O'Brien, MJ, Viguie, CA, Mazzeo, RS & Brooks, GA (1993) Carbohydrate dependence during marathon running. Medicine and Science in Sports and Exercise 25, 1009–1017.Google ScholarPubMed
Odland, LM, Heigenhauser, GJF, Wong, D, Hillidge-Horvat, MG & Spriet, LL (1998) Effects of increased fat availability on fat-carbohydrate interaction during prolonged exercise in men. American Journal of Physiology 274, R894–R902.Google ScholarPubMed
Olsson, AG, Eklund, B, Kaijser, L & Carlson, LA (1975) Extraction of endogenous plasma triglycerides by working human forearm muscle in the fasting state. Scandinavian Journal of Clinical and Laboratory Investigation 35, 231–236.CrossRefGoogle ScholarPubMed
Pearce, FJ & Connett, RJ (1980) Effect of lactate and palmitate on substrate utilisation of isolated rat soleus. American Journal of Physiology 238, C149–C159.CrossRefGoogle ScholarPubMed
Pernow, B & Saltin, B (editors) (1971) Muscle Metabolism during Exercise. Advances in Experimental Medicine and Biology, Vol. 11. New York: Plenum Press.CrossRefGoogle Scholar
Poole, DC, Gaesser, A, Hogan, C, Knight, DR & Wagner, PD (1992) Pulmonary and leg VO2 during submaximal exercise: implications for muscular efficiency. Journal of Applied Physiology 72, 805–810.CrossRefGoogle ScholarPubMed
Price, TB, Rothman, DL & Shulman, RG (1999) NMR of glycogen in exercise. Proceedings of the Nutrition Society 58, 851–859.CrossRefGoogle ScholarPubMed
Rådegran, G (1997) Ultrasound doppler estimates of femoral artery blood flow during dynamic knee extensor exercise in humans. Journal of Applied Physiology 83, 1383–1388.CrossRefGoogle ScholarPubMed
Rådegran, G (1999) Limb and skeletal muscle blood flow measurements at rest and during exercise in human subjects. Proceedings of the Nutrition Society 58, 887–898.CrossRefGoogle ScholarPubMed
Ray, CA & Dudley, GA (1998) Muscle use during dynamic knee extension: Implication for perfusion and metabolism. Journal of Applied Physiology 85, 1194–1197.CrossRefGoogle ScholarPubMed
Richardson, RS, Poole, DC, Knight, DR, Kurdak, SS, Hogan, MC, Grassi, B, Johnson, EC, Kendrick, KF, Erickson, BK & Wagner, PD (1993) High muscle blood flow in man: is maximal O2 extraction compromised. Journal of Applied Physiology 75, 1911–1916.CrossRefGoogle Scholar
Richardson, RS & Saltin, B (1998) Human blood flow and metabolism studied in the isolated quadriceps muscle. Medicine and Science in Sports and Exercise 30, 28–33.CrossRefGoogle Scholar
Richter, EA, Kiens, B, Galbo, H & Saltin, B (editors) (1998) Skeletal Muscle Metabolism in Exercise and Diabetes. Advances in Experimental Medicine and Biology, Vol. 441. New York: Plenum Press.Google Scholar
Rohen, JW & Yokochi, C (1988) Color Atlas of Anatomy. A Photographic Study of the Human Body. New York: Igaku-Shion Medical Publishers Inc.Google Scholar
Saltin, B & Gollnick, PD (1988) Fuel for muscular exercise. Role of carbohydrate. In Exercise, Nutrition and Energy Metabolism, pp. 45–71 [Horton, ES and Terjung, RL, editors.] New York: Macmillan Publishing Co.Google Scholar
Saltin, B & Kalsson, J (1971) Muscle glycogen utilisation during work of different intensities. In Muscle Metabolism During Exercise. Advances in Experimental Medicine and Biology, Vol. 11, pp. 289–299 [Pernow, B and Saltin, B, editors.] New York: Plenum Press.CrossRefGoogle Scholar
Savard, GK, Nielsen, B, Laszczynska, J, Larsen, BE & Saltin, B (1988) Muscle blood flow is not reduced in humans during moderate exercise and heat stress. Journal of Applied Physiology 64, 649–657.CrossRefGoogle Scholar
Seltzer, WK, Angelini, C, Dhariwal, G, Ringel, SP & McCabe, ERB (1989) Muscle glycerol kinase in Duchenne dystrophy and glycerol kinase deficiency. Muscle and Nerve 12, 307–313.CrossRefGoogle ScholarPubMed
Sidossis, LS, Coggan, AR, Gastadelli, A & Wolfe, RR (1995) A new correction factor for use in tracer estimations of plasma fatty acid oxidation. American Journal of Physiology 269, E649–E656.Google ScholarPubMed
Sjöström, M, Fridén, J & Ekblom, B (1982) Fine structural details of human muscle fibres after fibre type specific glycogen depletion. Histochemistry 76, 425–438.CrossRefGoogle ScholarPubMed
Staron, RS, Hikida, RR, Murray, TF & Hagerman, MT (1989) Lipid depletion and repletion in skeletal muscle following a marathon. Journal of Neurology Science 94, 29–40.CrossRefGoogle ScholarPubMed
Toews, C (1966) Evidence for the metabolism of glycerol by skeletal muscle and the presence of a muscle nicotinamide-adenine nucleotide phosphate-dependent glycerol dehydrogenase. Biochemical Journal 98, 27c–29c.CrossRefGoogle Scholar
Turcotte, LP, Richter, EA & Kiens, B (1992) Increased plasma FFA uptake and oxidation during prolonged exercise in trained vs. untrained humans. American Journal of Physiology 262, E791–E799.Google ScholarPubMed
Van, der Vusse GJ & Reneman, RS (1996) Lipid metabolism in muscle. In Handbook of Physiology. A Critical, Comprehensive Presentation of Physiological Knowledge and Concepts, pp. 952–994 [Rowell, LB and Shepard, JT, editors.] New York: Oxford University Press.Google Scholar
van Hall, G (1999) Correction factors for 13C-labelled substrate oxidation at whole-body and muscle level. Proceedings of the Nutrition Society 58, 979–986.CrossRefGoogle ScholarPubMed
Wahren, J (1967) Quantitative aspects of blood flow and oxygen uptake in the human forearm during rhythmic exercise. Acta Physiologica Scandinavica 67, Suppl. 269, 5–88.Google Scholar
Wahren, J, Alborg, G & Jorfeldt, L (1971) Glucose metabolism during exercise in man. Journal of Clinical Investigation 50, 2715–2725.CrossRefGoogle ScholarPubMed
Wendling, PS, Peters, SJ, Heigenhauser, GJF & Spriet, LL (1996) Variability of triacylglycerol content in human skeletal muscle biopsy samples. Journal of Applied Physiology 81, 1150–1155.CrossRefGoogle ScholarPubMed
Zierler, KI (1961) Theory of the use of arteriovenous concentration differences for measuring metabolism in steady state and non-steady state. Journal of Clinical Investigation 40, 2111–2125.CrossRefGoogle Scholar
Zuntz, N (1901) Ueber die bedeutung der vershiedenen nährstoffe als erzeuger der muskulkraft (An analysis of the value of various nutrients to generate muscle tone). Archiv für die Gesammte Physiologie 83, 557–571.CrossRefGoogle Scholar