Baseline Muscle Mass Is a Poor Predictor of Functional Overload-Induced Gain in the Mouse Model

Abstract

Genetic background contributes substantially to individual variability in muscle mass. Muscle hypertrophy in response to resistance training can also vary extensively. However, it is less clear if muscle mass at baseline is predictive of the hypertrophic response. The aim of this study was to examine the effect of genetic background on variability in muscle mass at baseline and in the adaptive response of the mouse fast- and slow-twitch muscles to overload. Males of eight laboratory mouse strains: C57BL/6J (B6, n = 17), BALB/cByJ (n = 7), DBA/2J (D2, n = 12), B6.A-(rs3676616-D10Utsw1)/Kjn (B6.A, n = 9), C57BL/6J-Chr10A/J/NaJ (B6.A10, n = 8), BEH+/+ (n = 11), BEH (n = 12), and DUHi (n = 12), were studied. Compensatory growth of soleus and plantaris muscles was triggered by a 4-week overload induced by synergist unilateral ablation. Muscle weight in the control leg (baseline) varied from 5.2 ± 07 mg soleus and 11.4 ± 1.3 mg plantaris in D2 mice to 18.0 ± 1.7 mg soleus in DUHi and 43.7 ± 2.6 mg plantaris in BEH (p < 0.001 for both muscles). In addition, soleus in the B6.A10 strain was ~40% larger (p < 0.001) compared to the B6. Functional overload increased muscle weight, however, the extent of gain was strain-dependent for both soleus (p < 0.01) and plantaris (p < 0.02) even after accounting for the baseline differences. For the soleus muscle, the BEH strain emerged as the least responsive, with a 1.3-fold increase, compared to a 1.7-fold gain in the most responsive D2 strain, and there was no difference in the gain between the B6.A10 and B6 strains. The BEH strain appeared the least responsive in the gain of plantaris as well, 1.3-fold, compared to ~1.5-fold gain in the remaining strains. We conclude that variation in muscle mass at baseline is not a reliable predictor of that in the overload-induced gain. This suggests that a different set of genes influence variability in muscle mass acquired in the process of normal development, growth, and maintenance, and in the process of adaptive growth of the muscle challenged by overload.

Forced Running Endurance Is Influenced by Gene(s) on Mouse Chromosome 10

“…The between strain difference remained robust and highly significant even following adjustments for body weight. Consistently with our recent observation in a separate study involving the same strains (Kilikevicius et al, 2016), it also emerged that soleus muscle weight was higher in B6.A10 compared to the B6 mice.…”

“…A difference in soleus muscle weight between the B6 and B6.A10 strains (Table 1) provides further support to recently reported observation between the same strains (Kilikevicius et al, 2016). Albeit a ~13% increase in soleus of B6.A10 strain is less extensive than ~40% reported in that study, collectively these findings are consistent with a notion that A/J variant of one or more chromosome 10 genes confer an increase in soleus weight.…”

Extracellular matrix remodelling is associated with muscle force increase in overloaded mouse plantaris muscle

“…Although the increase in total muscle weight and force was similar, the proportional increase in these parameters was much lower in Mstn À/À mice as compared to WT mice. Similar findings for muscle mass were seen in muscles from another mouse strain, the BEH mice [57], which also carry a loss-of-function mutation in Mstn. In BEH mice, however, maximal muscle force did not increase at all following overload, leading to a strong decrease in specific force [58].…”

Endurance exercise plus overload induces fatigue resistance and similar hypertrophy in mice irrespective of muscle mass

“…While many studies of concurrent training have been completed in both humans and rodents (Castoldi et al., 2013; Hickson, 1980; Methenitis, 2018), the effect of baseline muscle mass/FCSA on the response to combined hypertrophic and endurance stimuli is yet to be studied. Therefore, the aim of the present study was to determine the effects of combining a hypertrophic stimulus with endurance exercise on FCSA, muscle mass, oxidative capacity, capillarisation and contractile properties in three mouse strains with a 5‐fold difference in plantaris muscle mass: Berlin High (BEH), Berlin Low (BEL) and C57BL/6J (C57) (Kilikevicius, Bunger, & Lionikas, 2016). The BEH mouse strain has a large muscle mass and FCSA, due to myostatin dysfunction and long‐term selection for a large muscle mass (Lionikas et al., 2013b), while the BEL strain has a small muscle mass and small fibres (Lionikas et al., 2013b).…”