Dexamethasone-induced muscle atrophy in rats: effects of age and vitamin D deficiency

Background and Objectives: Since skeletal muscle plays an important role in energy metabolism, human health is supported by maintaining a suitable amount of the muscle. Age-related muscle loss is known as sarcopenia. Recent studies have suggested that vitamin D (VD) deficiency is related to sarcopenia, but mechanisms responsible for VD to maintain skeletal muscle are not clear. It has been reported that an overdose of dexamethasone (DEX) causes muscle atrophy and promotes the branched-chain amino acids (BCAAs) catabolism, suggesting that accelerated catabolism of the amino acids contributes to muscle atrophy. Therefore, the present study aimed to examine effects of VD deficiency on the BCAA catabolism and DEX-induced muscle atrophy in rats.We conducted 2 experiments. In Experiment 1, 9-week-old male rats were divided into two groups and either saline or DEX (600 µg/kg body weight) was intraperitoneally administered at 10:00 a.m. for consecutive 5 days. In Experiment 2, 5-week-old male rats were divided into two groups and fed either a control diet (AIN93G) or a VD-deficient diet (D18121302) for 8 weeks. At 14 weeks of age, each group of rats was divided into two subgroups, and then rats were given saline or DEX as in Experiment 1. On the final day of the experiment, rats were fasted for 6 hours and anesthetized with isoflurane, and then blood and tissues were collected.DEX administration decreased muscle weights of tibialis anterior and gastrocnemius+plantaris by 29% and by 23%, respectively, in Experiment 1, and by 18% and by 17%, respectively, in Experiment 2. Soleus muscle weight was not affected by DEX administration in either experiment. These results suggesting that the skeletal muscles consisting mainly of white muscles in younger rats are susceptible to the DEX treatment. The DEX treatment significantly elevated the concentrations of plasma insulin and BCAAs, the former suggesting insulin resistance and the latter suggesting promotion of protein degradation. The VD deficiency did not affect muscle atrophy or plasma concentrations of insulin and BCAAs, suggesting VD deficiency did not promote DEX-induced muscle atrophy or insulin resistance.