Skeletal muscle cellularity and glycogen distribution in the hypermuscular Compact mice

Abstract

The TGF-beta member myostatin acts as a negative regulator of skeletal muscle mass. The Compact mice were selected for high protein content and hypermuscularity, and carry a naturally occurring 12-bp deletion in the propeptide region of the myostatin precursor. We aimed to investigate the cellular characteristics and the glycogen distribution of the Compact tibialis anterior (TA) muscle by quantitative histochemistry and spectrophotometry. We have found that the deficiency in myostatin resulted in significantly increased weight of the investigated hindlimb muscles compared to wild type. Although the average glycogen content of the individual fibers kept unchanged, the total amount of glycogen in the Compact TA muscle increased two-fold, which can be explained by the presence of more fibers in Compact compared to wild type muscle. Moreover, the ratio of the most glycolytic IIB fibers significantly increased in the Compact TA muscle, of which glycogen content was the highest among the fast fibers. In summary, myostatin deficiency caused elevated amount of glycogen in the TA muscle but did not increase the glycogen content of the individual fibers despite the marked glycolytic shift observed in Compact 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).…”

“…Nonfasting 3-to 4-moold male mice were euthanized, and tissues were frozen in liquid nitrogen. Total glycogen amount of the tissue samples was measured as glucose residues by hexokinase/glucose-6-phosphate dehydrogenase assay (Roche) following acidic hydrolysis, as described earlier (22).…”

“…Glycogen content of the liver samples was visualized on 5-m-thin cryosections by periodic acid Schiff (PAS) staining, as described previously (22).…”

“…Myostatin was reported to influence the glycogen content of C2C12 myoblasts (9), and muscle glycogen was reduced in type 2 diabetes mellitus (15). Previously, we have shown that Compact tibialis anterior muscle contains more glycogen than that of BALB/c (22). To distinguish the role of Compact mutation and the Compact genetic background in the regulation of glycogen stores, here we compared the glycogen content of Compact, congenic wildtype, and BALB/c muscles.…”