Key result
Myostatin-deficient mice lost more mass from muscles expressing fast type IIb myofibres during hind limb suspension compared to wild-type mice, but recovered muscle mass after 7 days of reloading.
Myostatin deficiency exacerbates skeletal muscle atrophy during unloading via enhanced atrogenic signaling, but does not impair muscle mass recovery upon reloading.
Myostatin deficiency may worsen unloading atrophy in fast fibers without impairing recovery; hypothesis-generating for human disuse interventions.
Skeletal muscles of myostatin null (Mstn(-/-)) mice are more susceptible to atrophy during hind limb suspension (HS) than are muscles of wild-type mice. Here we sought to elucidate the mechanism for this susceptibility and to determine if Mstn(-/-) mice can regain muscle mass after HS. Male Mstn(-/-) and wild-type mice were subjected to 0, 2 or 7 days of HS or 7 days of HS followed by 1, 3 or 7 days of reloading (n = 6 per group). Mstn(-/-) mice lost more mass from muscles expressing the fast type IIb myofibres during HS and muscle mass was recovered in both genotypes after reloading for 7 days. Concentrations of MAFbx and MuRF1 mRNA, crucial ligases regulating the ubiquitin-proteasome system, but not MUSA1, a BMP-regulated ubiquitin ligase, were increased more in muscles of Mstn(-/-) mice, compared with wild-type mice, during HS and concentrations decreased in both genotypes during reloading. Similarly, concentrations of LC3b, Gabarapl1 and Atg4b, key effectors of the autophagy-lysosomal system, were increased further in muscles of Mstn(-/-) mice, compared with wild-type mice, during HS and decreased in both genotypes during reloading. There was a greater abundance of 4E-BP1 and more bound to eIF4E in muscles of Mstn(-/-) compared with wild-type mice (P<0.001). The ratio of phosphorylated to total eIF2α increased during HS and decreased during reloading, while the opposite pattern was observed for rpS6. Concentrations of myogenic regulatory factors (MyoD, Myf5 and myogenin) mRNA were increased during HS in muscles of Mstn(-/-) mice compared with controls (P<0.001). We attribute the susceptibility of skeletal muscles of Mstn(-/-) mice to atrophy during HS to an up- and downregulation, respectively, of the mechanisms regulating atrophy of myofibres and translation of mRNA. These processes are reversed during reloading to aid a faster rate of recovery of muscle mass in Mstn(-/-) mice.
No takes yet. Share an insight, caveat, or question.
Smith et al. (2014) studied Muscle atrophy (n=72). Hind limb suspension (HS) and reloading vs. Wild-type mice was evaluated on Change in muscle mass and gene expression. Myostatin-deficient mice lost more mass from muscles expressing fast type IIb myofibres during hind limb suspension compared to wild-type mice, but recovered muscle mass after 7 days of reloading.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: