Long-Term Exercise Mitigates Energy Expenditure and Inflammatory Responses Induced by Sleep Deprivation in Mice

<b>Background</b>: Sleep deprivation (SD), defined as the disruption or loss of normal sleep, negatively affects energy metabolism, immune function, and gut microbiota in both humans and animals. Although SD has detrimental effects, it is often unavoidable due to work or study demands. Exercise has been shown to improve sleep quality, regulate metabolism, and enhance immune function. However, whether exercise can mitigate the adverse effects of unavoidable SD remains unclear. <b>Methods</b>: To explore the protective effects of exercise against SD-induced gut microbiota and metabolic dysfunction, mice were randomly assigned to four groups: control (CTR), exercise (EXE), SD, and exercise + SD (EXE + SD). Inflammatory markers and gut microbiota composition were analyzed to assess the impacts of SD and exercise interventions. <b>Results</b>: The inflammatory levels and energy metabolism in SD mice were significantly increased compared to those in CTR mice. Compared with SD mice, EXE + SD mice had a more stable gut microbiota structure and higher butyrate levels. Meanwhile, the inflammatory response caused by SD was also inhibited by exercise preconditioning. Both lipopolysaccharide inhibitors injection and butyrate supplementation can partially alleviate the elevation of inflammatory response and energy metabolism caused by SD. <b>Conclusion</b>: The inflammation and energy metabolism disorders in mice caused by SD can be inhibited by exercise preconditioning through stabilizing the structure of gut microbiota. This protective effect is highly likely related to the increase in butyric acid levels caused by exercise.