Mediator complexes regulate skeletal muscle metabolic function: a review / 药学学报

Mediator complexes involved in skeletal muscle metabolic processes have become a hot research topic in recent years. The mediator complex is a multi-protein complex which participates in transcription by bridging specific transcription factors and basal transcriptional machinery (RNA polymerase II). Mediator complexes are involved in regulating the expression of transcription factors related to skeletal muscle metabolism and muscle fiber transformation, such as PPARs and PGC1α. These mediators participate in skeletal muscle glucose metabolism by regulating glucose transporter GLUT4 and key transcription factors of metabolic pathways. In addition, they regulate metabolic diseases by regulating the expression of PPARγ, UCP-1 and other genes involved in skeletal muscle lipid metabolism and mitochondrial functions. This article reviews the mechanism and effects of mediator complexes on skeletal muscle metabolism.

Regulation and mechanism of glucocorticoids on skeletal muscle metabolism / 中国药理学通报

Glucocorticoids ( GCs) have important regulatory effects on skeletal muscle metabolism. GCs can inhibit skeletal muscle glucose uptake and glycogen synthesis, and improve blood glucose levels by inhibiting Pik3rl expression, inhibiting insulin signaling pathway, or promoting pyruvate dehydrogenase kinase 4 expression; GCs can inhibit skeletal muscle lipid metabolism , causing the accumulation of lipid metabolism intermediates diacylglycerol and ceramides, and inducing skeletal muscle insulin resistance; GCs can induce MuRFl and MAFbx expression by promoting FoxO expression, activating the ubiquitin-proteasome system and autophagy lysosome system, and activating oxidative stress system, or promote the protein decomposi-tion of skeletal muscle by up-regulating C/EBPp expression; GCs can also inhibit the mTOR pathway by promoting myostatin and Pik3rl expression and inhibit skeletal muscle protein synthesis by up-regulating KLF-15 expression. This article explores the effects of GCs on skeletal muscle metabolism and its molecular mechanisms by tracking the latest developments at home and a-broad, which will provide reference for the clinical application of GCs.

Assessment of Effect of Pulmonary Rehabilitation on Skeletal Muscle Metabolism by 31P Magnetic Resonance Spectroscopy / 결핵

Pulmonary rehabilitation has been known to improve dyspnea and exercise tolerance in patients with chronic lung disease, although it does not improve pulmonary function. The mechanism of this improvement is not clearly explained till now ; however some authors suggested that the improvement in the skeletal muscle metabolism after the rehabilitation could be a possible mechanism. The metabolc changes in skeletal muscle in patients with COPD are characterized by impaired oxidative phosphorylation which causes early activation of anaerobic glycolysis and excess lactate production with exercise. In order to evaluate the change in the skeletal muscle metabolism as a possible cause of the improvement in the exercise tolerance after the rehabilitation, noninvasive 31P magnetic resonance spectroscopy(MRS) of the forearm flexor muscle was performed before and after the exercise training in nine patients with chronic lung disease who have undertaken intensive pulmonary rehabilitation for 6 weeks. 31P MRS was studied during the sustained isometric contraction of the dominant forearm flexor muscles up to the exhaustion state and the recovery period. Maximal voluntary contraction(MVC) force of the muscle was measured before the isometric exercise, and then 30% of MVC force was constantly loaded to each patient during the isometric exercise. After the exercise training, exercise endurance of upper and lower extremities and 6 minute walking distance were significantly increased(p<0.05). There were no differences of baseline intracellular pH (pHi) and inorganic phosphate/phosphocreatine(Pi/PCr). After rehabilitation pHi at the exercise and the exhaustion state showed a significant increase(6.91+/-0.1 to 6.99+/-0.1 and 6.76+/-0.2 to 6.84+/-0.2 respectively, p<0.05). Pi/PCr at the exercise and the recovery rate of pHi and Pi/PCr did not show significant differences. These results suggest that the delayed intracellular acidosis of skeletal muscle may contribute to the improvement of exercise endurance after pulmonary rehabililtation.

Assessment of Abnormality in Skeletal Muscle Metabolism in Patients with Chronic Lung Desease by 31P Magnetic Resonance Spectroscopy / 결핵

The functional derangement of skeletal muscles which may be attributed to chronic hypoxia has been accepted as a possible mechanism of exercise impairment in patients with chronic obstructive pulmonary disease (COPD). The metabolc changes in skeletal muscle in patients with COPD are characterized by impaired oxidative phosphorylation early activation of anaerobic glycolysis and excessive lactate and hydrogen ion production with exercise. But the cause of exercise limitation in patients with chronic lung disease without hypoxia has not been known. In order to evaluate the change in the skeletal muscle metabolism as a possible cause of the exercise limitation in chronic lung disease patients without hypoxia, we compared the muscular metabolic data of seven male patients which had been derived from noninvasive 31P magnetic resonance spectroscopy(MRS) with those of five age-matched normal male control persons. 31P MRS was studied during the sustained isometric contraction of the dominant forearm flexor muscles up to the exhaustion state and the recovery period. Maximal voluntatry contraction(MVC) force of the muscle was measured before the isometric exercise, and the 30% of MVC force was constantly loaded to each patient during the isometric exercise. There were no differences of intracellular pH (pHi) and inorganic phosphate/phosphocreatine (Pi/PCr) at baseline, exhaustion state and recovery period between two groups. But pHi during the exercise was lower in patients group than the control group (p<0.05). Pi/PCr during the exercise did not show significant difference between two groups. These results suggest that the exercise limitation in chronic lung disease patients without hypoxia also could be attributed to the abnormalities in the skeletal muscle metabolism.