Functional overload in ground squirrel plantaris muscle fails to induce myosin isoform shifts

Abstract

We performed 2 wk of mechanical overload by synergist ablation on plantaris muscles from a small rodent hibernator, Spermophilus lateralis. While this muscle displays prominent myosin heavy-chain (MyHC) isoform shifts during hibernation, sensitivity to mechanical loading as a stimulus for muscle mass and isoform plasticity has not been demonstrated. Squirrel muscles, whether during hibernation or not, potentially are less sensitive to mechanical unloading, but we hypothesized that increased loading would produce the typical mammalian response of greater plantaris mass and MyHC shifts. Mechanical overload produced a 50% increase in muscle mass but, surprisingly, no changes in MyHC isoform protein or mRNA expression, despite previously observed fast-to-slow MyHC isoform switching during hibernation. Citrate synthase enzyme activity, as well as mRNA expression of creatine kinase and the muscle growth factor myostatin, were all unchanged. The mRNA expression of critical muscle atrophy genes decreased by 50% during hypertrophy, including ubiquitin ligases MuRF1 and MAFbx, and the related transcription factor FOXO-1a. Insulin-like growth factor (IGF-1) and hypoxia-inducible factor (HIF-1alpha) mRNA expression was elevated by 400% and 150%. Fast-to-slow MyHC isoform shifts appear unnecessary to support the increased recruitment of the plantaris muscle, shifts which are seen in other rodent models. Our results are consistent with muscular activity during interbout arousals as a potential mechanism to preserve muscle mass, but illustrate the primary importance of other seasonal factors besides patterns of muscle activation which must act in concert to alter MyHC isoforms and muscle fiber type during hibernation.

Systematic review of the synergist muscle ablation model for compensatory hypertrophy

“…Tenotomy has the disadvantage of the rapid reconnection of the cut tendon, which limits functionality. 65 Most commonly studied muscles Compensatory hypertrophy by the ablation of synergists is an efficient model for studies on muscle hypertrophy, 2,3,7,[10][11][12][13][14][15][16][17][18][19][20] as the fast increase in muscle mass reduces the duration of the experiment. In recent years, changes have occurred in the standard of surgery (bilateral or unilateral) and the relationship between the number of days and increase in muscle mass, which justifies this systematic review.…”

“…2,3,7,[10][11][12][13][14][15][16][17][18][19][20] The most studied muscles are plantar flexors in the rear paw of rats. As skeletal muscle has different types of fibers (type I [slow--twitch] and type II [fast-twitch -IIa, IIb, IIx/IId]), 21 a number of authors justify the choice of the plantaris muscle due to its diversity of fiber types (type I: 8 ± 2%; type IIA: 19 ± 3%; type IIB/D: 74 ± 4%) and its different adaptation possibilities.…”

Migration- and exercise-induced changes to flight muscle size in migratory birds and association withIGF1andmyostatinmRNA expression

“…Exercise and training have also been associated with decreased expression of myostatin mRNA and protein in humans (Roth et al, 2003;Raue et al, 2006;Louis et al, 2007) and rats (Matsakas et al, 2005;Matsakas et al, 2006;Heinemeier et al, 2007), although this finding has not been consistent. In response to overloading of the plantaris muscle in ground squirrels (Callospermophilus lateralis), muscle hypertrophy was observed without a change in the expression of myostatin mRNA (Choi et al, 2009). In other mammalian studies, muscle myostatin expression has paradoxically increased in response to training or overloading in skeletal or cardiac muscle (Sakuma et al, 2000;Willoughby, 2004;Matsakas et al, 2006;Jensky et al, 2007;Jensky et al, 2010).…”

“…Previous work in mammals has demonstrated that IGF1 expression in muscles is induced by muscle contraction and during compensatory hypertrophy (DeVol et al, 1990;Heinemeier et al, 2007;Choi et al, 2009). IGF1 is known to stimulate protein synthesis in myocytes and also satellite cell proliferation, leading to hypertrophy (Rennie et al, 2004).…”

“…IGF1 is secreted and binds to IGF1 receptors (IGFR) in muscles in an autocrine or paracrine manner, stimulating pathways leading to differentiation, proliferation and anabolism (Adams, 1998). Like myostatin, IGF1 has been proposed to regulate mammalian muscle size in response to exercise and muscle loading (DeVol et al, 1990;Adams, 1998;Rennie et al, 2004;Heinemeier et al, 2007;Choi et al, 2009). In birds (primarily from studies in embryonic or neonate poultry), myostatin and IGF1 similarly appear to have functions in mediating muscle hypertrophy and hyperplasy during development (Guernec et al, 2003;Duclos, 2005;Sato et al, 2006;Kim et al, 2007;McFarland et al, 2007).…”