Muscle Rev-erb controls time-dependent adaptations to chronic exercise in mice

Area of Science:

• Chronobiology
• Exercise Physiology
• Metabolic Health

Background:

• Optimal timing for chronic exercise training remains unclear.
• Diurnal variations in muscle performance and training adaptations are not well understood.
• The role of the circadian clock in muscle function and exercise response needs further investigation.

Purpose of the Study:

• To determine the optimal time of day for low-intensity treadmill training in mice.
• To elucidate the underlying mechanisms of diurnal variations in muscle performance and training adaptations.
• To investigate the role of muscle-specific circadian clock genes, Rev-erbα/β, in these processes.

Main Methods:

• Low-intensity, low-volume treadmill training in mice.
• Muscle contractile performance and systemic glucose tolerance assessments.
• Muscle-specific knockout of Rev-erbα/β (Rev-MKO) mice.
• Multi-omics and metabolic measurements.

Main Results:

• Treadmill training before sleep improved muscle performance and glucose tolerance more than training after waking.
• Baseline muscle strength was higher, while endurance was lower before sleep compared to after waking.
• Muscle-specific knockout of Rev-erbα/β abolished diurnal variations in training response and baseline muscle function.
• Rev-erb suppressed fatty acid oxidation and promoted carbohydrate metabolism before sleep.

Conclusions:

• The muscle-autonomous circadian clock, regulated by Rev-erb, dictates diurnal variations in muscle function and training adaptations.
• Feeding and locomotor behaviors are not the primary drivers of these diurnal variations.
• Findings have significant implications for optimizing exercise timing in metabolic disorders and sports medicine, particularly with Rev-erb agonists.