Fiber Type and Stimulus Determine Progression of Skeletal Muscle Atrophy.

Area of Science:

• Muscle physiology
• Molecular biology
• Comparative pathology

Background:

• Skeletal muscle atrophy is a global health issue impacting quality of life.
• Atrophy is often treated as a single disorder, but causes like malnutrition and disuse lead to varied progression.
• Direct comparisons of atrophy progression and fiber type effects from different stimuli are lacking.

Purpose of the Study:

• To directly compare muscle atrophy progression induced by fasting versus disuse.
• To analyze differential effects on skeletal muscle fiber types.
• To generate a transcriptomic resource for future research on muscle atrophy.

Main Methods:

• Two cohorts of mice were subjected to either fasting (up to 72 hours) or hindlimb suspension (HS; up to 28 days).
• Tibialis anterior (TA), extensor digitorum longus (EDL), and soleus muscles were collected at various timepoints for RNA sequencing.
• Atrophy progression and gene expression were compared across muscle fiber types and stimuli.

Main Results:

• Fasting caused significant body weight loss and TA muscle mass reduction, with minimal soleus impact.
• Hindlimb suspension led to greater soleus atrophy but had negligible effects on TA.
• Gene expression analysis revealed distinct transcriptional changes: fasting upregulated fatty acid metabolism, while HS increased neuronal activity.

Conclusions:

• Muscle atrophy progression is stimulus- and fiber type-dependent.
• This study provides a unique dataset for comparing atrophy stimuli.
• Therapeutic strategies for muscle atrophy may need to be personalized to the underlying cause.