Skeletal muscle substrate metabolism during exercise: methodological considerations

The aim of the present article is to evaluate critically the various method s employed in studies designed to quantify precisely skeletal muscle substr ate utilization during exercise. In general, the pattern of substrate utili zation during exercise can be described well from O-2 uptake measurements a nd 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 measureme nts for O-2 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, th e use of isotopes opens up further possibilities for the estimation of oxid ation rates of various substrates. There are several methodological concern s to be aware of when studying the metabolic response to exercise in human subjects. These concerns include: (1) the muscle mass involved in the exerc ise is largely unknown (bicycle or treadmill). Moreover, whether the muscle sample obtained from a limb muscle and the substrate and metabolite concen trations are representative can be a problem; (2) the placement of the veno us catheter can be critical, and it should be secured so that the blood sam ple represents blood from the active muscle with a minimum of contamination from other muscles and tissues; (3) the use of net limb glycerol release t o estimate lipolysis is probably not valid (triacylglycerol utilization by muscle), since glycerol can be metabolized in skeletal muscle; (4) the prec ision of blood-borne substrate concentrations during exercise measured by a -v difference is hampered since they become very small due to the high bloo d flow. Recommendations are given in order to obtain more quantitative and conclusive data in studies investigating the regulatory mechanisms for subs trate choice by muscle.