Low-Intensity Running and High-Intensity Swimming Exercises Differentially Improve Energy Metabolism in Mice With...

Area of Science:

• Neurodegenerative Diseases
• Metabolic Disorders
• Exercise Physiology

Background:

• Spinal Muscular Atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by SMN1 gene mutations, leading to motor neuron loss.
• SMA patients exhibit metabolic alterations, including glucose intolerance and hyperlipidemia, suggesting a role for energy homeostasis in disease progression.
• Previous studies showed mild SMA-like mice tolerate low-intensity running and high-intensity swimming exercise programs.

Purpose of the Study:

• To investigate if exercise-induced benefits in mild SMA-like mice are associated with improved metabolic status.
• To evaluate the effects of aerobic and mixed aerobic/anaerobic exercise on lipid metabolism, glucose homeostasis, and mitochondrial function in SMA models.

Main Methods:

• Comparison of metabolic status (lipid metabolism, glucose homeostasis, energy expenditure) between untrained and exercised mild SMA-like mice.
• Assessment of mitochondrial function using electron microscopy, respiratory chain complex expression, and enzymatic activity measurements.
• Evaluation of oxygen consumption and energy expenditure during spontaneous activity and exercise.

Main Results:

• Untrained SMA-like mice displayed dysregulated lipid metabolism (increased lipogenesis, adipocyte deposits) and high oxygen consumption with increased beta-oxidation.
• Both running and swimming protocols improved lipid metabolism and glucose homeostasis, enhancing oxygen consumption efficiency.
• High-intensity swimming yielded more significant benefits, including sustained high lipid oxidation and reduced negative impacts on mitochondrial respiratory chain complexes and maximal oxygen consumption.

Conclusions:

• Active physical exercise, particularly high-intensity protocols like swimming, induces beneficial metabolic adaptations at systemic and cellular levels in SMA models.
• Exercise improves lipid metabolism, glucose homeostasis, and mitochondrial function, counteracting metabolic dysregulation observed in SMA.
• Findings support the integration of exercise, including high-intensity training, into long-term care strategies for SMA patients, potentially in conjunction with SMN-overexpressing therapies.