Skeletal Muscle Fuel Selection Occurs at the Mitochondrial Level

Abstract

Mammals exponentially increase the rate of carbohydrate oxidation as exercise intensity rises, while birds combust lipid almost exclusively while flying at high percentages of aerobic capacity. The fuel oxidized by contracting muscle depends on many factors: whole-body fuel storage mass, mobilization, blood transport, cellular uptake, and substrate selection at the level of the mitochondrion. We examined the fuel preferences of mitochondria isolated from mammalian and avian locomotory muscles using two approaches. First, the influence of substrates on the kinetics of respiration (K m,ADP and V max ) was evaluated. For all substrates and combinations, K m,ADP was generally twofold higher in avian mitochondria. Second, fuel competition between pyruvate, glutamate and/or palmitoyl-L-carnitine at three levels of ATP free energy was determined using the principle of mass balance and the measured rates of O 2 consumption and metabolite accumulation/utilization. Avian mitochondria strongly spared pyruvate from oxidation when another substrate was available and fatty acid was the dominant substrate, regardless of energy state. Mammalian mitochondria exhibited some preference for fatty acid over pyruvate at lower flux (higher energy state), but exhibited a much greater tendency to select pyruvate and glutamate when available. Studies in sonicated mitochondria revealed twofold higher electron transport chain electron conductance in avian mitochondria. We conclude that substantial fuel selection occurs at the level of the mitochondrial matrix and that avian flight muscle mitochondria are particularly biased toward the selection of fatty acid, possibly by facilitating high β-oxidation flux by maintaining a more oxidized matrix.

Control of Cardiac Mitochondrial Fuel Selection by Calcium

“…In summary, our results show that a fuel selection switch from fatty acids to greater fractional utilization of pyruvate occurs with increasing ATP demand rate and calcium in cardiac mitochondria in vitro. These results mirror previous observation obtained using isolated skeletal muscle mitochondria [35]. Finally, these observations are consistent with our hypothesis that calcium contributes to modulating the switch from fatty acid to carbohydrate oxidation with increasing ATP demand in vivo.…”

“…At the highest added calcium employed, the relative contribution of pyruvate to oxidative metabolism in mixed substrate conditions increases from 55 ± 20% at the leak state (ADP infusion rate of I = 0 nmol•min -1 •(U CS) -1 to 83 ± 10% at an ADP infusion rate of I = 234 nmol•min -1 •(U CS) -1 (approximately 1/3 of Vmax) to 85 ± 10% at I = 356 nmol•min -1 •(U CS) -1 (approximately 1/2 of Vmax). These findings are analogous to the trend of increasing fraction of pyruvate utilization with increasing demand observed by Kuzmiak-Glancy and Willis [35] in skeletal muscle mitochondrial from rat and sparrow.…”

“…During exercise (high ATP demand) the ratio flips, with the majority of acetyl-CoA supplied from oxidation of carbohydrates [33,34]. This phenomenon of increasing relative contribution from carbohydrate oxidation with increasing ATP synthesis rate is recapitulated in vitro in isolated mitochondria from skeletal muscle [35].…”

Cinnamon hydro alcoholic extract increased expression level of UCP3 gene in skeletal muscle of obese male Wistar Rats

“…In mammalian and avian Skeletal muscle fuel selection occurs at the mitochondrial level. different muscles according their structure and function might be have different number of mitochondria and use different sources of fuels like lipids and glucose (Kuzmiak-Glancy and Willis, 2014). As a different structure and function of Epitroch and Gracilis skeletal muscles and similarity of these muscles in human and rat we examine the effect of cinnamon extract on UCP3 expression level in those different muscles.…”

A Simple Hydraulic Analog Model of Oxidative Phosphorylation

“…As developed in Messer et al (42), this clamp has complete concentration control of the ATP turnover loop, leaving mitochondria, therefore, with complete flux control (5). This procedure was utilized in the experiments depicted in Table 1 and Figures 3D and 5 and has also been used to investigate fuel selection, insulin resistance, oxygen uptake kinetics, and Ca 2+ activation of skeletal muscle mitochondria from rats, pigs, sparrows, and/or humans (15, 16, 36–38, 42). …”