Would Combination Be Better: Swimming Exercise and Intermittent Fasting Improve High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Obese Rats via the miR-122-5p/SREBP-1c/CPT1A Pathway.

Background: Swimming and intermittent fasting can both improve obesity-induced NAFLD, but which of the two is more effective and whether the combination of the two has a superimposed effect is inconclusive. Methods: The model of NAFLD in obese rats was established by a high-fat diet and performed swimming, intermittent fasting, and a combination of both interventions for 8 weeks. Serum lipids and enzyme activity were measured by an automatic biochemical analyzer. Liver morphostructural analysis was observed by transmission electron microscopy, and morphology was observed by HE staining. RT‒PCR was used to detect the mRNA level. Results: Morphology and microstructure of the liver of model rats were impaired, with the upregulation of miR-122-5p, SREBP-1c, FASN and ACC1. Eight weeks of swimming exercise, intermittent fasting and the combination of both attenuate these effects, manifested by the downregulation of miR-122-5p and upregulation of CPT1A mRNA levels. There was no significant stacking effect of the combination of the swimming and intermittent fasting interventions. Conclusion: NAFLD leads to pathology in model rats. Eight weeks of swimming exercise, intermittent fasting and the combination of both can inhibit miR-122-5p and improve hepatic lipid metabolism, while no significant additive effects of combining the interventions were found.

Formulation of precise exercise intervention strategy for adolescent depression.

The high incidence of adolescent depression has become the focus of social and academic attention. Exercise is an important method to improve adolescent depression, but its intervention effect is still controversial. This study first compares and analyzes the relevant studies at home and abroad and finds that exercise prescription in adolescent depression intervention is not accurate enough. A meta-analysis was conducted to develop a precise exercise intervention strategy for adolescent depression. Firstly, this thesis identified how to optimize five elements (exercise intensity, exercise frequency, exercise time, exercise cycle, and exercise type) of exercise prescription to improve depression in adolescents. This is the problem. Furthermore, the concept of "precision exercise" was proposed, and a precision exercise intervention strategy (moderate-intensity aerobic exercise for 8-10 weeks, 3 times/week, 45-50 min/time) was constructed to improve adolescent depression. This paper also presents research that strengthens the cross-sectional research and empirical research on adolescent depression and establishes a precision exercise prescription database for adolescent depression in China. In conclusion, this study not only puts forward the concept of "precision exercise" but also constructs a precision exercise intervention strategy for adolescent depression, which has important theoretical and practical significance for improving the high incidence of adolescent depression.

Exercise alleviates renal interstitial fibrosis by ameliorating the Sirt1-mediated TGF-ß1/Smad3 pathway in T2DM mice.

Background: Renal interstitial fibrosis is the pathophysiological basis of type 2 diabetes mellitus (T2DM). Exercise appears to improve kidney interstitial fibrosis in T2DM, in which silent information regulator factor 2-related enzyme 1 (Sirt1) is a critical regulator. However, the role of Sirt1 in mediating exercise on renal tissue as well as its mechanism remains unknown. Methods: T2DM mouse models were created using a high-fat diet mixed with streptozotocin, followed by 8 weeks of treadmill exercise and niacinamide (Sirt1 inhibitor) intervention. Kits for detecting biochemical indices of renal function were used. The pathological appearance and severity of renal tissue were examined using hematoxylin and eosin, Masson and immunohistochemical staining. The mRNA and protein expression of relevant signaling pathway factors were determined to use real-time reverse transcriptase-polymerase chain reaction and western blotting. Results: T2DM can promote renal interstitial fibrosis, increase kidney index, serum creatinine, blood urea nitrogen and 24 h urinary total protein and cause pathological changes in renal tissue and affect renal function. After 8 weeks of exercise intervention, the biochemical indicators in the kidney of T2DM mice were decreased, Sirt1 expression was increased, the expression of TGF-ß1, Smad3, collagen type I (COL1) and collagen type III (COL3) were decreased, and the renal interstitial fibrosis, renal tissue structural lesions and renal function were improved. However, after the nicotinamide intervention, renal interstitial fibrosis of T2DM mice was aggravated, and the improvement effect of exercise on renal interstitial fibrosis of T2DM mice was abolished. Conclusion: The upregulation of Sirt1 expression by exercise can inhibit the transforming growth factor ß1/Smad3 pathway, thereby inhibiting the expression and deposition of COL1 and COL3 in renal interstitium, thereby improving renal interstitial fibrosis in T2DM.

Study on the Mechanism for SIRT1 during the Process of Exercise Improving Depression.

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-1ß (IL-1ß)), 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.

High intensity interval training ameliorates cognitive impairment in T2DM mice possibly by improving PI3K/Akt/mTOR Signaling-regulated autophagy in the hippocampus.

Exercise can improve cognitive impairment in type 2 diabetes mellitus (T2DM). However, the underlying mechanisms are not clear, and the optimal exercise modes for cognitive benefits are controversial. The aim of this study was to investigate the effects of high-intensity interval training (HIIT) and moderate-intensity interval training (MICT) on cognitive function and the PI3K/Akt/mTOR pathway as well as autophagy in T2DM mice. The results showed that 8 weeks of HIIT and MICT intervention could improve the spatial learning and memory ability of T2DM mice, as determined by the Morris water maze (MWM) test. Both HIIT and MICT similarly improved autophagy, as evidenced by increased Beclin1 and LC3 II/I ratios and decreased p62. Meanwhile, HIIT and MICT inhibited excessive activation of the PI3K/Akt/mTOR pathway in the hippocampus. HIIT induced a larger reduction in mTOR activity than MICT. This study suggests that both HIIT and MICT can alleviate cognitive decline induced by T2DM, improve autophagy in the hippocampus, and downregulate the excessive activation of the PI3K/Akt/mTOR signaling pathway, with similar effects.

Exercise improves bone formation by upregulating the Wnt3a/ß-catenin signalling pathway in type 2 diabetic mice.

BACKGROUND: The bone formation ability of type 2 diabetes is inhibited, and exercise can effectively improve the bone formation of T2DM. However, whether exercise can mediate the Wnt3a/ß-catenin pathway to improve the mechanism of bone formation and metabolism still needs further research. METHODS: A T2DM mouse model was established by a high-fat diet and STZ injection, and the mice were trained with swimming and downhill running exercise. Alizarin red staining is used to observe the changes of the left femoral trabecular bone; micro-CT is used to analyze the trabecular and cortical BMD, BV/TV, BS/BV, BS/TV, Tb.Th, Tb.Sp; the ALP staining of skull was used to observe the changes in ALP activity of bone tissues at the skull herringbone sutures; ALP staining was performed to observe the changes in the number of OBs and ALP activity produced by differentiation; Quantitative PCR was used to detect mRNA expression; Western blot was used to detect protein expression levels. RESULTS: When the Wnt3a/ß-catenin pathway in the bones of T2DM mice was inhibited, the bone formation ability of the mice was significantly reduced, resulting in the degradation of the bone tissue morphology and structure. Swimming caused the significant increase in body weight and Runx2 mRNA expression, while downhill running could significantly decrease the body weight of the mice, while the tibia length, wet weight, and the trabecular morphological structure of the distal femur and the indexes of bone histomorphology were significantly improved by activating the Wnt3a/ß-catenin pathway. CONCLUSIONS: Bone formation is inhibited in T2DM mice, leading to osteoporosis. Downhill running activates the Wnt3a/ß-catenin pathway in the bones of T2DM mice, promotes OB differentiation and osteogenic capacity, enhances bone formation metabolism, and improves the bone morphological structure.

Bone Autophagy: A Potential Way of Exercise-Mediated Meg3/P62/Runx2 Pathway to Regulate Bone Formation in T2DM Mice.

BACKGROUND: Meg3 has been shown to attenuate T2DM bone autophagy by activating p62 to inhibit bone formation. However, whether exercise can reverse this process to promote T2DM bone formation and its mechanism remains unknown. METHODS: A T2DM mouse model was established by a high-fat diet and STZ injection, and the mice were trained with 8-week HIIT and downhill running exercise. Micro-CT was used to scan the bone microstructure. Bone morphology was observed by HE staining, and the osteoblast (OB) activity in bones was observed by AKP staining. Calcium ion and phosphorus concentration in serum was detected by ELISA; RT-PCR was used to detect the mRNA level, and Western blot was used to detect the protein level of related indexes in Meg3/p62/Runx2 pathway. RESULTS: The inhibition of bone autophagy, in the bones of T2DM mice, resulted in the degradation of the bone tissue morphology and structure, with the increase of the expressions of Meg3, PI3K, Akt, mTOR, p62 and NF-κB. However, 8-week HIIT and downhill running could reverse this process, especially downhill running, manifested with the up-regulation of miR-16 mRNA level, along with Beclin-1, LC3 II and Runx2 mRNA and protein level. CONCLUSION: T2DM leads to pathology in model mice. Eight-week HIIT and downhill running exercise can inhibit Meg3, activate autophagy of osteoblasts and promote bone formation in T2DM mice.

The efficacy and safety of exercise for prevention of fall-related injuries in older people with different health conditions, and differing intervention protocols: a meta-analysis of randomized controlled trials.

BACKGROUND: Whether exercise prevents fall-related injuries in different health conditions and with different training protocols is still unclear. This study aimed to determine the effect of exercise on fall-related injuries by participant characteristics and divergent exercise protocols. The safety and compliance of exercise were also examined. METHODS: Electronic database searches were conducted in PubMed, Web of Science, and EMBASE for randomised controlled trials that evaluated the influence of exercise on fall-induced injuries in older people. RESULTS: Twenty-five trials met the inclusion criteria. Exercise significantly reduced the risk of fall-related injuries in older adults, risk ratio (RR) 0.879 [95% confidence interval (CI) 0.832-0.928]. Among the injuries, events needing medical care or resulting fractures were also decreased by exercise intervention, with RR 0.681 (0.562-0.825) and 0.561 (0.366-0.860), respectively. When analysis was stratified by participant characteristics and exercise protocols, we found that participants at high risk of falling, or with osteoporosis, were sensitive to exercise intervention. Combined exercise protocols and balance training were the most effective exercise types in reducing fall-related injuries. Exercise-associated beneficial effects were even significant in very old people (≥80 years) and across the duration of interventions (< 6 months, 6 to 12 months and ≥ 12 months). Exercise only generated a very low injury rate per participant year (0.002, 95% CI 0-0.05) and showed relatively good compliance of exercise (as reported in the included papers) (78.5, 95% CI 72.8-84.2%). CONCLUSIONS: Exercise is effective in preventing fall-induced injuries across a variety of baseline participant characteristics and exercise protocols. Exercise was associated with a low injury rate and had a good compliance, suggesting it is a feasible approach to managing fall-related injuries.

Treadmill Exercise Decreases Aß Deposition and Counteracts Cognitive Decline in APP/PS1 Mice, Possibly via Hippocampal Microglia Modifications.

Recent studies have suggested that exercise may be beneficial for delaying or attenuating Alzheimer's disease (AD). However, the underlying mechanisms were not clear. Microglia-mediated neuroinflammation is suggested to play an important role in the pathology of AD. The present study investigated the beneficial effects of treadmill exercise on amyloid-ß (Aß) deposition and cognitive function in amyloid precursor protein (APP)/PS1 mice in the early stage of AD progression and microglia-mediated neuroinflammation was mainly analyzed. The results demonstrated that 12 weeks of treadmill exercise preserved hippocampal cognitive function in APP/PS1 mice and substantially suppressed Aß accumulation in the hippocampus. Treadmill exercise significantly inhibited neuroinflammation, which was characterized by a remarkably reduced expression of pro-inflammatory factors and increased expression of anti-inflammatory mediators in the hippocampus, resulting from a shift in activated microglia from the M1 to M2 phenotype. Treadmill exercise also attenuated oxidative stress presented by a marked reduction in methane dicarboxylic aldehyde (MDA) level and dramatically elevated SOD and Mn-SOD activities in the hippocampus. These findings suggest that treadmill exercise can effectively prevent the decrease in hippocampal-dependent cognitive function and Aß deposits in early AD progression possibly via modulating microglia-mediated neuroinflammation and oxidative stress.

Treadmill exercise inhibits amyloid-ß generation in the hippocampus of APP/PS1 transgenic mice by reducing cholesterol-mediated lipid raft formation.

The deposition of amyloid-ß (Aß) is one of the major pathological hallmarks of Alzheimer's disease (AD), and a higher cholesterol level is involved in the deposition of Aß. Previous evidence suggested that exercise exerts neuroprotective effects in a variety of AD models. In the present study, we investigated the effects of a 12-week treadmill exercise program on Aß deposits in amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and the potential underlying mechanism. After 12 weeks of exercise, Aß deposits were significantly decreased in the hippocampus. Meanwhile, the amyloidogenic pathway of APP metabolism was inhibited, which was associated with a decrease in BACE1 expression. The APP metabolism mediated by the nonamyloidogenic pathway, as indicated by the increase in ADAM10 levels. Coincidentally, exercise reduced the cholesterol level, as evidenced by a significant decrease in the total cholesterol level and the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, as well as a reduction in the number of lipid rafts, as evidenced by a significant decrease in the flotillin 1 level. These finding suggested that the 12-week treadmill exercise program reduced Aß deposition in the hippocampus of APP/PS1 mice, possibly by regulating ADAM10 and BACE1 levels and by decreasing cholesterol-mediated lipid raft formation, indicating that exercise represents a therapeutic intervention to treat AD.