Parallel Regulatory Mechanisms Between Anabolic And Catabolic Signaling Pathway During Maintenance Of Skeletal Muscle Mass

Abstract

Skeletal muscle mass and fiber size is regulated by the combined effects between protein synthesis and degradation. Here, we show the parallel regulatory mechanism between anabolic and catabolic signaling pathway during maintenance and atrophy in skeletal muscle. PURPOSE: Our aim in this study is to investigate the effects of intermittent reloading during hindlimb suspension (HS) to the changes in skeletal muscle fiber size and intracellular signaling pathways. METHODS: Male Wister rats were subjected to 7 days of ground control or HS treatment. During the experimental period, the animals in HS group were intermittently reloaded for 4h/day. After each experimental period, the antigravitational soleus muscle was analyzed. Fiber cross-sectional area (CSA) was determined by histochemical analysis. Activation state of anabolic (Akt and mTOR) and catabolic (IkB-NFkB, FOXO and MAPK P38) signaling pathways were assessed by western blotting and electrophoretic mobility shift assay. RESULTS: Following 7 days of HS treatment, muscle fiber atrophy (decrease in relative muscle mass: 0.28 mg/g in the HS group vs. 0.36 mg/g in the control group, p<0.05; decrease in fiber CSA: 1682.6 μm2 in the HS group vs. 2673.0 μm2 in the control group, p<0.05) and a decrease in phosphorylation levels of anabolic signaling pathway (Akt and mTOR) were observed. Additionally, increases in NFkB nuclear protein content were also confirmed. In contrast, intermittent reloading during HS treatment attenuated the muscle fiber atrophy (0.33 mg/g and 2067.5 μm2) and recovered the phosphorylation levels of anabolic signaling. Levels of nuclear NFkB were suppressed with the effects of intermittent reloading. CONCLUSIONS: These results suggest that the maintenance and decrease in skeletal muscle mass are regulated by the synergy between anabolic and catabolic signaling pathways. Supported by Grants #15200048, #17-7279 and in part by the Nishihira/Tsukuba Project of COE (Center of Excellence) from the Japan Ministry of Education, Culture, Sports, Science and Technology.