The utility of the rodent synergist ablation model in identifying molecular and cellular mechanisms of skeletal muscle hypertrophy

Abstract

Skeletal muscle exhibits remarkable plasticity to adapt to stimuli such as mechanical loading. The mechanisms that regulate skeletal muscle hypertrophy due to mechanical overload have been thoroughly studied. Remarkably, our understanding of many of the molecular and cellular mechanisms that regulate hypertrophic growth were first identified using the rodent synergist ablation (SA) model and subsequently corroborated in human resistance exercise training studies. To demonstrate the utility of the SA model, we briefly summarize the hypertrophic mechanisms identified using the model and the following translation of these mechanism to human skeletal muscle hypertrophy induced by resistance exercise training.

Keywords: mTOR signaling; microRNAs; protein synthesis; ribosome biogenesis; satellite cell fusion.

Graphical abstract

Figure 1.

Different models of mechanical overload. Mouse hindlimb anatomy shown, highlighting gastrocnemius complex consisting of gastrocnemius (GAS), plantaris (PLA), and soleus (SOL) muscles. Excision parts for tenotomy—GAS tendon; partial synergist ablation (SA)—2/3 GAS; complete SA—soleus, 2/3 of GAS. Created with Biorender.com.

Figure 2.

Synergist ablation discovery timeline. Timeline showing year of skeletal muscle hypertrophy mechanism identified by synergist ablation (left) and the corresponding year that the mechanism was identified in response to human resistance exercise training (right). Created with Biorender.com.