Dexamethasone impairs muscle energetics, studied by 31P NMR, in rats

Abstract

Aims/hypothesis: Glucocorticoid treatments are associated with increased whole-body oxygen consumption. We hypothesised that an impairment of muscle energy metabolism can participate in this increased energy expenditure. Methods: To investigate this possibility, we have studied muscle energetics of dexamethasone-treated rats (1.5 mg kg −1 day −1 for 6 days), in vivo by 31 P NMR spectroscopy. Results were compared with control and pair-fed (PF) rats before and after overnight fasting. Results: Dexamethasone treatment resulted in decreased phosphocreatine (PCr) concentration and PCr:ATP ratio, increased ADP concentration and higher PCr to γ-ATP flux but no change in β-ATP to β-ADP flux in gastrocnemius muscle. Neither 4 days of food restriction (PF rats) nor 24 h fasting affected high-energy phosphate metabolism. In dexamethasone-treated rats, there was an increase in plasma insulin and non-esterified fatty acid concentration. Conclusions/ interpretation: We conclude that dexamethasone treatment altered resting in vivo skeletal muscle energy metabolism, by decreasing oxidative phosphorylation, producing ATP at the expense of PCr.

Impaired Resting Muscle Energetics Studied by 31P‐NMR in Diet‐induced Obese Rats

“…Acidosis in muscle at rest has been observed in streptozotocin‐diabetic rats (33). By contrast with this result, but in accordance with the model of insulin resistance induced by dexamethasone treatment (30), intracellular pH averaged 7.2 and was not decreased in our experimental groups compared to control. Finally, it is possible that the results obtained from ex vivo muscles systematically differ from the composition in the intact in vivo muscle because of incubation conditions or damage during preparation (see ref.…”

“…The current high‐energy phosphate levels obtained in control Wistar rats are similar to recent data obtained in gastrocnemius of adult Sprague‐Dawley rats. In this model, the intracellular concentrations in the fasted state averaged 8.5 mmol/l ATP, 36 mmol/l PCr and 3.9 mmol/l P i (30). In accordance with these data, it has been previously reported that P i concentration in rat resting muscle is near 3 mmol/l (31).…”

Creatine intake attenuates corticosteroid-induced impairment of voluntary running in hamsters

“…We may guess that non-investigated biochemical disorders could have contributed to the present findings. A recent paper supports this hypothesis, since a 6 d dexamethasone treatment in rats led to altered resting gastrocnemius metabolism by decreasing oxidative phosphorylation, producing ATP at the expense of PCr (Dumas et al 2005).…”

“…Therefore, we assume that the preservation of spontaneous running in hamsters treated with dexamethasone and Cr may be better explained by an increase in the intracellular pool of these substances. This phenomenon, most probably, would antagonize the already described metabolic changes induced by dexamethasone in skeletal muscles (Dumas et al 2005).…”

How Do Glucocorticoids Regulate Lipid Metabolism?

“…It has also been reported that GCs can induce excessive NEFA oxidation that can lead into muscle insulin resistance [ 108 ] and perturbation of equilibrium between fats and glucose as energy sources [ 109 ]. In rats, GC-induced insulin resistance has been shown to increase serum insulin and NEFA levels and decrease oxidative phosphorylation by producing ATP from phosphocreatine [ 110 ]. How GC/GR signaling exactly orchestrates these entire events in skeletal muscles, with the possibility of inter-organ cross-talk, remains to be studied.…”