Sympathetic denervation impairs skeletal muscle function by disrupting NMJs and reducing CPT1 activity, which decreases mitochondrial fatty acid oxidation.
Sympathetic innervation is crucial for maintaining skeletal muscle mitochondrial metabolic function and performance during exercise.
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The sympathetic nervous system (SNS) is recognized for its role in the physiological regulation of organs, such as heart, vasculature and lungs, and has emerged as a potential player in skeletal muscle metabolic and neuromuscular junction (NMJ) health. However, the mechanism through which SNS signaling influences skeletal muscle function and adaptation to exercise remains unclear. Using molecular, electrophysiological, immunohistochemical, and high-resolution respirometry techniques, we tested the role of sympathetic innervation to skeletal muscle in response to exercise. Our findings reveal that sympathetic denervation disrupts the NMJ, reducing motor and sympathetic receptor expression, with concomitant deficits in skeletal muscle function. Mechanistically, these deficits are linked to diminished CPT1 enzyme activity, which impairs long-chain fatty acid-mediated oxidation in skeletal muscle mitochondria. These findings reveal a key role for sympathetic innervation in maintaining mitochondrial metabolic function and by extension, skeletal muscle performance, offering novel insight into the interplay between the SNS, exercise, and muscle mitochondria.
Owyoung et al. (Wed,) reported a other. Sympathetic denervation impairs skeletal muscle function by disrupting NMJs and reducing CPT1 activity, which decreases mitochondrial fatty acid oxidation.