Low dose formoterol administration improves muscle function in dystrophic mdx mice without increasing fatigue

Area of Science:

• Pharmacology
• Muscle Physiology
• Neuromuscular Disorders

Background:

• Beta(2)-adrenoceptor agonists can induce muscle hypertrophy.
• Formoterol, a beta(2)-agonist, has shown anabolic effects in rats at low doses.
• Muscular dystrophies involve progressive muscle wasting and weakness.

Purpose of the Study:

• To investigate the effects of low-dose formoterol on muscle function in dystrophic mdx mice.
• To assess formoterol's impact on muscle mass, fiber size, force production, and fatigability.
• To explore formoterol's influence on ubiquitin-proteasome pathway components.

Main Methods:

• Ten-week-old male mdx and wild-type mice received formoterol (25 micro g/kg/day) intraperitoneally for 4 weeks.
• Muscle mass, fiber size (diaphragm, EDL, soleus), and maximum force were measured.
• Muscle fatigability and ubiquitin-related markers were assessed.

Main Results:

• Formoterol treatment increased muscle mass and median fiber size in diaphragm, EDL, and soleus muscles of both wild-type and mdx mice.
• Maximum force production capacity was enhanced in skeletal muscles of both groups.
• Low-dose formoterol did not increase muscle fatigability and reduced ubiquitinated proteins in wild-type mice diaphragms.

Conclusions:

• Low-dose formoterol exhibits potent anabolic effects on skeletal muscle, surpassing older beta(2)-agonists.
• Formoterol demonstrates significant therapeutic potential for treating muscular dystrophies and other muscle-wasting disorders.
• The findings support formoterol as a promising agent for enhancing muscle function and combating muscle wasting.