Loss of myostatin expression alters fiber-type distribution and expression of myosin heavy chain isoforms in slow- and fast-type skeletal muscle

Abstract

Myostatin (Mstn) is a member of the transforming growth factor-beta family that negatively regulates skeletal muscle mass. Mstn knockout mice have greater skeletal muscle mass than wild-type littermates. We investigated the effect of Mstn on fiber type by comparing adult muscles from the murine Mstn knockout with wild-type controls. Based on myofibrillar ATPase staining, the soleus of Mstn knockout mice displays a larger proportion of fast type II fibers and a reduced proportion of slow type I fibers compared with wild-type animals. Based on staining for succinate dehydrogenase (SDH) activity, a larger proportion of glycolytic fibers and a reduced proportion of oxidative fibers occur in the extensor digitorum longus (EDL) of Mstn knockouts. These differences in distribution of fiber types are accompanied by differences in the expression of myosin heavy chain (MHC) isoforms. In both Mstn knockout soleus and EDL, larger numbers of faster MHC isoforms are expressed at the expense of slower isoforms when compared with wild-type littermates. Thus, the absence of Mstn in the knockout mouse leads to an overall faster and more glycolytic muscle phenotype. This muscle phenotype is likely a consequence of developmental processes, and inhibition of Mstn in adults does not cause a transformation to a more fast and glycolytic phenotype. Our findings suggest that myostatin has a critical role in regulating the formation, proliferation, or differentiation of fetal myoblasts and postnatal fibers.

Myostatin-deficient mice exhibit reduced insulin resistance through activating the AMP-activated protein kinase signalling pathway

“…5h). However, there is an anomaly; as others and we have shown [39][40][41], [42]. In addition to the reduced adiposity, Mstn −/− mice and, for that matter, mice treated with sActIIBR, the MSTN antagonist, have improved tolerance to glucose and increased sensitivity to insulin (Fig.…”

Inhibition of Activin Receptor Type IIB Increases Strength and Lifespan in Myotubularin-Deficient Mice

“…11 While there is some evidence that myostatin inhibition during development can produce increased numbers of type 2b fibers in skeletal muscle, 38 treatment of wild-type and Mtm1␦4 mice with ActRIIB-mFC did not change the number or percentage of type 1, 2a, and 2b fibers in the quadriceps muscles. These findings, which are consistent with a recent report of the effects of ActRIIB-mFC treatment in wild-type mouse muscle, 17 support the theory that myocyte hyperplasia or changes in fiber type distribution do not occur with postnatal inhibition of myostatin or ActRIIB.…”

Regeneration of Reinnervated Rat Soleus Muscle Is Accompanied by Fiber Transition Toward a Faster Phenotype

“…cDNAs for MHCI, MHCIIA, MHCIIX, and MHCIIB were amplified at 94C for 1 min, at the appropriate annealing temperature for 1 min, and at 72C for 1 min using 2 U/tube Taq polymerase (Table 1) (Zádor et al 1996;Jaschinski et al 1998;Girgenrath et al 2005). We applied two different sets of primers for MHCIIB amplification, both of which produced essentially the same amplification pattern, outlined in the Results section.…”