TheCompactMutation of Myostatin Causes a Glycolytic Shift in the Phenotype of Fast Skeletal Muscles

Abstract

Myostatin is an important negative regulator of skeletal muscle growth. The hypermuscular Compact ( Cmpt) mice carry a 12-bp natural mutation in the myostatin propeptide, with additional modifier genes being responsible for the phenotype. Muscle cellularity of the fast-type tibialis anterior (TA) and extensor digitorum longus (EDL) as well as the mixed-type soleus (SOL) muscles of Cmpt and wild-type mice was examined by immunohistochemical staining of the myosin heavy chain (MHC) proteins. In addition, transcript levels of MHC isoforms were quantified by qPCR. Based on our results, all investigated muscles of Cmpt mice were significantly larger compared with that of wild-type mice, as characterized by fiber hyperplasia of different grades. Fiber hypertrophy was not present in TA; however, EDL muscles showed specific IIB fiber hypertrophy while the (I and IIA) fibers of SOL muscles were generally hypertrophied. Both the fast TA and EDL muscles of Cmpt mice contained significantly more glycolytic IIB fibers accompanied by a decreased number of IIX and IIA fibers; however, this was not the case for SOL muscles. In summary, despite the variances found in muscle cellularity between the different myostatin mutant mice, similar glycolytic shifts were observed in Cmpt fast muscles as in muscles from myostatin knockout mice.

Myostatin propeptide mutation of the hypermuscularCompactmice decreases the formation of myostatin and improves insulin sensitivity

“…We and others have reported earlier that the Compact mice are hypermuscular (3,22,35), and cellularity of the Compact skeletal muscles shows increased ratio of glycolytic fibers in rectus femoris, longissimus dorsi (35), and tibialis anterior (3,22) muscles. Decreased specific force (1) and reduced calcium release from sarcoplasmic reticulum (5) were reported in Compact muscles.…”

“…1A) was selected and inbred in a long-term selection experiment in Berlin, Germany (8,50). The origin of the Hungarian subpopulation of the Compact line was described earlier (3,22). The BALB/c mice carrying wild-type myostatin were obtained from the Biological Research Centre of the Hungarian Academy of Sciences (Szeged, Hungary).…”

Hypermuscular mice with mutation in the myostatin gene display altered calcium signalling

“…; Baan et al . ) as well as a large increase in the ATP cost of contraction (Giannesini et al . ), it was tempting to assume that an altered acto‐myosin interaction would be responsible for the reduced specific force since the former can be accompanied by modifications in myosin expression.…”

Skeletal muscle cellularity and glycogen distribution in the hypermuscular Compact mice

“…The origin and the selection procedure of the Compact mice were described by Baán and colleagues. 16 Briefly, the Compact line was selected initially in Berlin on the basis of high protein mass and hypermuscularity. The Hungarian subpopulation of this Compact line was inbred and kept for more than 20 years in the Institute for Animal Biology, Agricultural Animal Center (Gödöllő, Hungary), while they have been breeding since 2010 in the Department of Biochemistry, Faculty of General Medicine, University of Szeged (Szeged, Hungary).…”

“… 12 Hypermuscularity caused by Compact mutation results from muscle fiber hyperplasia rather than hypertrophy, and muscle metabolism shifted towards glycolytic direction. 15 , 16 We hypothesized that not only the increased protein amount but also the higher glycogen content may account for the increased muscle weight of the Compact s; therefore, in this present study we aimed to analyze the muscle cellularity of the Compact mice focusing on the glycogen content and the fiber-type specific glycogen distribution. Here we show that the glycogen content of the IIB fibers was the highest among the fast fibers in the tibialis anterior (TA) muscle.…”