Sahlin K, Mogensen M, Bagger M, Fernström M, Pedersen PK. The potential for mitochondrial fat oxidation in human skeletal muscle influences whole body fat oxidation during low-intensity exercise. Am J Physiol Endocrinol Metab 292: E223-E230, 2007. First published August 22, 2006; doi:10.1152/ajpendo.00266.2006.-The purpose of this study was to investigate fatty acid (FA) oxidation in isolated mitochondrial vesicles (mit) and its relation to training status, fiber type composition, and whole body FA oxidation. Trained (V O2 peak 60.7 Ϯ 1.6, n ϭ 8) and untrained subjects (39.5 Ϯ 2.0 ml ⅐ min Ϫ1 ⅐ kg Ϫ1 , n ϭ 5) cycled at 40, 80, and 120 W, and whole body relative FA oxidation was assessed from respiratory exchange ratio (RER). Mit were isolated from muscle biopsies, and maximal ADP stimulated respiration was measured with carbohydrate-derived substrate [pyruvate ϩ malate (Pyr)] and FA-derived substrate [palmitoyl-L-carnitine ϩ malate (PC)]. Fiber type composition was determined from analysis of myosin heavy-chain (MHC) composition. The rate of mit oxidation was lower with PC than with Pyr, and the ratio between PC and Pyr oxidation (MFO) varied greatly between subjects (49 -93%). MFO was significantly correlated to muscle fiber type distribution, i.e., %MHC I (r ϭ 0.62, P ϭ 0.03), but was not different between trained (62 Ϯ 5%) and untrained subjects (72 Ϯ 2%). MFO was correlated to RER during submaximal exercise at 80 (r ϭ Ϫ0.62, P ϭ 0.02) and 120 W (r ϭ Ϫ0.71, P ϭ 0.007) and interpolated 35% V O2 peak (r ϭ Ϫ0.74, P ϭ 0.004). ADP sensitivity of mit respiration was significantly higher with PC than with Pyr. It is concluded that MFO is influenced by fiber type composition but not by training status. The inverse correlation between RER and MFO implies that intrinsic mit characteristics are of importance for whole body FA oxidation during low-intensity exercise. The higher ADP sensitivity with PC than that with Pyr may influence fuel utilization at low rate of respiration. oxidative phosphorylation; training FATTY ACID (FA) OXIDATION contributes significantly to whole body energy turnover during low-to moderate-intensity exercise, and a high rate of FA oxidation is of importance for performance during prolonged exercise. Furthermore, both fuel utilization and fuel storage are abnormal in patients with type 2 diabetes (21) and obesity (23). Despite intensive research, the mechanisms that regulate the relative contribution of fat and carbohydrate (CHO) in substrate oxidation remain unclear.FA oxidation is reduced, both in absolute and relative terms, at high exercise intensities, but there is no clear effect of exercise intensity on relative FA oxidation at low intensities [Ͻ50% of peak oxygen consumption (V O 2 peak )] (9, 50). Previous studies have shown that there are large interindividual variations in FA utilization both at rest and during exercise (14, 16), and there is evidence that FA oxidation is influenced by factors such as preceding diet, muscle glycogen content, exercise intensity, training status, traini...