Guo Z, Jensen MD. Arterio-venous balance studies of skeletal muscle fatty acid metabolism: what can we believe? Am J Physiol Endocrinol Metab 305: E925-E930, 2013. First published August 13, 2013; doi:10.1152/ajpendo.00346.2013.-The arterio-venous balance (A-V balance/difference) technique has been used by a number of groups, including ours, to study skeletal muscle fatty acid metabolism. Several lines of evidence indicate that, like glycogen, intramyocellular triglycerides (imcTG) are an energy source for local use. As such, the report that increased release of free fatty acids (FFA) via lipolysis from skeletal muscle, but not from adipose tissue, is responsible for the increased systemic lipolysis during IL-6 infusion in healthy humans is somewhat unexpected (26). It appears that given the complex anatomy of human limbs, as to be discussed in this review, it is virtually impossible to determine whether any fatty acids being released into the venous circulation of an arm or leg derive from the lipolysis of intermuscular fat residing between muscle groups, intramuscular fat residing within muscle groups (between epimysium and perimysium, or bundles), or the intramyocellular triglyceride droplets (imcTG). In many cases, it may even be difficult to be confident that there is no contribution of FFA from subcutaneous adipose tissue. This question is fundamentally important as one attempts to interpret the results of skeletal muscle fatty acid metabolism studies using the A-V balance technique. In this Perspectives article, we examine the reported results of fatty acid kinetics obtained using the techniques to evaluate the degree of and how to minimize contamination when attempting to sample skeletal muscle-specific fatty acids. arterio-venous difference; arterio-venous balance; leg; forearm; skeletal muscle; adipose; fatty acids
Terminology and ExpressionsFOR THE STUDY OF MUSCLE FATTY ACID METABOLISM, the leg arterio-venous (A-V) balance technique is commonly employed (17,19,20,22,26). It employs flexible catheters to collect blood samples from the femoral artery and femoral vein for the purpose of measuring the concentration of fatty acids. This information allows one to determine the net uptake or net release of fatty acids (mmol/l) based on the A-V concentration difference. If the difference is positive, it is a net uptake. If it is negative, it is a net release. Often, plasma or blood flow rate is determined simultaneously to calculate the rates of net uptake and net release of fatty acids across the leg (mmol/min). These parameters only provide one-way information, either release or uptake, but not both. To measure both directions, free fatty acid (FFA) tracers are required. By combining plasma flow, fatty acid concentrations, and the isotopic enrichment (with stable isotope) or specific activity (with radioactive isotope), the unidirectional uptake as well as the unidirectional release of fatty acids can be quantified (13,25). The term release and uptake with or without a preceding adjective "net" confers qui...