Physical exercise as a modulator of the sleep-obesity interaction: metabolic, neuroendocrine and circadian mechanisms

Obesity and sleep disturbances are highly prevalent chronic conditions that share multiple pathophysiological mechanisms, including chronic low-grade inflammation, neuroendocrine dysfunction, circadian misalignment, autonomic imbalance, insulin resistance, and metabolic dysregulation. These conditions establish a multidirectional relationship that contributes to the development and progression of cardiometabolic, respiratory, and psychological comorbidities. In this context, physical exercise (PE) is widely recognized as a non-pharmacological strategy for the prevention and treatment of obesity and sleep disturbances that simultaneously modulates these interconnected pathways while enhancing metabolic flexibility. Growing evidence also supports its role as a non-photic zeitgeber that synchronizes central and peripheral biological clocks, modulates clock gene expression, and influences metabolic responses according to the time of day it is performed. Through these multisystem adaptations, PE may interrupt the vicious cycle linking obesity and sleep disturbances, thereby improving metabolic health and reducing the burden of obesity-related comorbidities. This review discusses how PE modulates the multidirectional relationship between sleep and obesity through integrated multisystem adaptations, highlighting its potential to improve both sleep and overall health.