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

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Keywords: gut microbiota; inflammation; mice; moderate-intensity continuous training; sleep deprivation.

Figure 1

The effects of sleep deprivation on metabolism and inflammatory responses in mice: (A) body weight, (B) BMR after SD treatment, (C) daily average food intake, (D) body weight changes, (E) serum LPS level, (F) the gene expression level of IL-6 of muscle, (G–I) the protein levels of TLR4; NF-κB and IL-6 of muscle. Values are means ± SEM. *, p < 0.05, **, p < 0.01, ***, p < 0.001.

Figure 2

MICT prevented the impacts on inflammation and energy metabolism caused by SD: (A) body weight, (B) BMR, (C) daily average food intake, (D) body weight changes, (E) serum LPS level. (F) serumIL-6 level, (G–I) the protein levels of TLR4, NF-κB, and IL-6 of muscle. The labels above each column indicate the presence (+) or absence (−) of SD and Exe, respectively. Values are means ± SEM. *, p < 0.05, **, p < 0.01, ***, p < 0.001.

Figure 3

Influence of SD and MICT on the gut microbiota in mice. (A) Alpha diversity of bacterial communities across 4 groups based on Shannon score. (B) Principal coordinates analysis (PCoA) plots based on Bray–Curtis distance. (C) Differences in microbiota abundance of 4 groups. (D) Cladogram representing taxa enriched in the cecal microbiota community of the four groups detected by the LEfSe tool. (E) Relative abundance of the dominant genus. (F) Differential bacterial taxonomy was selected by LEfSe analysis with an LDA score of ≥3 in the cecal microbiota community of the four groups. (G) Lachnospiraceae_NK4A136_group, Lachnospiraceae_UCG-006 abundance. (H–J) SCFAs level in gut. (K) Correlation analysis among phenotypes and microbiota abundance. The abundance of bacterial genus within the red-framed area showed a significant negative correlation with both LPS and BMR. Values are means ± SEM. *, p < 0.05, **, p < 0.01, ***, p < 0.001.

Figure 4

Effects of butyrate gavage on in SD mice: (A) body weight, (B) BMR,(C) daily average food intake, (D) body weight changes, (E) serum LPS level, (F) serum IL-6 level, (G–I) the protein levels ofTLR4; NF-κB and IL-6 of muscle. Values are means ± SEM. *, p < 0.05, **, p < 0.01, ***, p < 0.001.

Figure 5

Influence of SD and butyrate gavage on gut microbiota in mice. (A) Alpha diversity of bacterial communities across two groups based on Shannon score. (B) Principal coordinates analysis (PCoA) plots based on Bray–Curtis distance. (C) Differences in microbiota abundance of 2 groups. (D) Difference in relative abundance of Lachnospiraceae_UCG-006. (E) Relative abundance of the dominant genus. (F) Differential bacterial taxonomy was selected by LEfSe analysis with an LDA score of ≥2.2 in the cecal microbiota community of the four groups. (G) Heatmap of top 50 different microbiota genera of 2 groups. Values are means ± SEM. *, p < 0.05.

Figure 6

Effects of inhibitor injection on SD mice: (A) body weight, (B) BMR, (C) daily average food intake, (D) body weight changes, (E) serum LPS level, (F) serum IL-6 level, (G–I) the protein levels of TLR4, NF-κB and IL-6 of muscle. Values are means ± SEM. *, p < 0.05, **, p < 0.01, ***, p < 0.001.