The mechanism behind the onset of depression has been the focus of current research in the neuroscience field. Silent information regulator 1 (SIRT1) is a key player in regulating energy metabolism, and it can regulate depression by mediating the inflammatory response (e.g., nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)), gene expression in the nucleus accumben (NAc) and CA1 region of the hippocampus (e.g., nescient helix-loop-helix2 (NHLH2), monoamine oxidase (MAO-A), and 5-Hydroxyindole-3-acetic acid (5-HIAA)), and neuronal regeneration in the CA3 region of the hippocampus. Exercise is an important means to improve energy metabolism and depression, but it remains to be established how SIRT1 acts during exercise and improves depression. By induction and analysis, SIRT1 can be activated by exercise and then improve the function of the hypothalamic–pituitary–adrenal (HPA) axis by upregulating brain-derived neurotrophic factors (BDNF), inhibit the inflammatory response (suppression of the NF-κB and TNF-α/indoleamine 2,3-dioxygenase (IDO)/5-Hydroxytryptamine (5-HT) pathways), and promote neurogenesis (activation of the insulin-like growth factor1 (IGF-1) and growth-associated protein-43 (GAP-43) pathways, etc.), thereby improving depression. The present review gives a summary and an outlook based on this finding and makes an analysis, which will provide a new rationale and insight for the mechanism by which exercise improves depression.

(1) Objective: To explore the change of bone resorption metabolism in T2DM mice as well as the effect of different exercise on the OC differentiation and bone resorption metabolism in T2DM mice through Sirt1/NF-κB pathway. (2) Methods: A total of 55 4-week-old male C57BL/6 mice were randomly divided into normal control group (NC) (12 mice) and T2DM modeling group (n=43). After modeling, the T2DM mice were randomized into T2DM control group (TDC, n=13), T2DM high-intensity intermittent exercise group (TDG, n=13) and T2DM downhill running group (TDP, n=14). Group TDG and group TDP were trained by 8-week high-intensity intermittent exercise and downhill running respectively. After the interventions, related factors in the bone were detected for mRNA expression by RT-PCR, and for protein expression by West-blotting technique. TRAP staining was used to detect the quantity of OCs and multinuclear OCs induced by BMM induced differentiation, and ELISA to detect the serum tartrate-resistant acid phosphatase (StrACP) activity. Groups of mice were observed for morphological structure of bone tissue by HE staining and Safranin O-Fast Green staining. (3) Results: Compared with group NC, the cancellous bone and cortical bone thickness were significantly degraded in TDC group, inhibition of OC differentiation in T2DM mice resulted in a decrease in serum StrACP activity, and down-regulation of Sirt1 expression in T2DM mice bone resulted in activation of the NF-κB pathway. After 8 weeks of training, the up-regulation of Sirt1 expression in the bone of TDG and TDP mice inhibited the NF-kB pathway, inhibited OC differentiation and serum AP activity in T2DM mice, and significantly improved the thickness of cancellous and cortical bone in the distal femur and tibia of T2DM mice. However, TDP is significantly better than TDG in improving the changes of the above related indicators. (4) Conclusion: The bone resorption/metabolism in T2DM mice was enhanced. Downhill running activated Sirt1 expression in the bone of T2DM mice, and then inhibited the NF-κB pathway, thus suppressing OC differentiation and bone resorption/metabolism, and its effect was better than that of high-intensity intermittent exercise.