Understanding Brain-Skeletal Muscle Crosstalk Impacting Metabolism and Movement

This perspective proposes a new interdisciplinary research direction—“Science and Engineering of Metabolism and Movement”—focused on systems-level mechanisms by which the brain and skeletal muscle coordinate metabolic regulation and movement. The authors outline a multi-focus program combining in vivo noninvasive neuroimaging (MEG,PET,fMRI) with in vitro microphysiological models (human primary neuron culture and muscle-on-a-chip) to interrogate bidirectional brain–muscle communication, including exercise-driven signaling (e.g., exosome-mediated effects on neuronal metabolism) and the coupled roles of mitochondria (ATP production) and myosin (mechanical work). The article emphasizes integrating advanced imaging (including expansion microscopy), biochemical and omics profiling (proteomics,lipidomics,miRNA), and computational systems biology (genome-scale metabolic models and flux balance analysis) to reconstruct brain and muscle metabolic states under sedentary versus mechanically exercised conditions and to identify mechanistic drivers of myopathy, neurodegeneration, and exercise adaptations.