miR-34a/TAN1/CREB Axis Engages in Alleviating Oligodendrocyte Trophic Factor-Induced Myelin Repair Function and Astrocyte-Dependent Neuroinflammation in the Early Stages of Alzheimer's Disease: The Anti-Neurodegenerative Effect of Treadmill Exercise.

Reduced myelin stability observed in the early stages of Alzheimer's disease leads to spatial learning and memory impairment. Exercise has been shown to protect nerves, reduce the risk of Alzheimer's disease, and strengthen synaptic connectivity. However, the underlying mechanisms of how exercise can promote myelin repair and coordinate inflammation and proliferation are still uncertain. In this study, we conducted histological and biochemical assays of cortical lysates after behavioral testing to detect pathological changes, myelin sheath thickness, and mRNA and protein levels. It is notable that D-galactose model mice exhibited elevated miRNA-34a levels, overactive astrocytes, decreased myelin staining scores, increased apoptosis, and decreased synaptic plasticity in the brain. Significantly, after eight weeks of exercise, we observed improvements in LFB scores, NeuN( +) neuron counts, and myelin basic protein (MBP) expression. Additionally, exercise promoted the expression of oligodendrocyte markers Olig2 and PDFGR-α associated with brain proliferation, and improved spatial cognitive function. Furthermore, it decreased the inflammation caused by astrocyte secretions (TNF-α, Cox-2, CXCL2). Interestingly, we also observed downregulation of miR-34a and activation of the TAN1/PI3K/CREB signaling pathway. Our data shed light on a previously unsuspected mechanism by which exercise reduces miR-34a levels and protects neuronal function and survival by preventing excessive demyelination and inflammatory infiltration in the CNS.

Zebrafish Congenital Heart Disease Models: Opportunities and Challenges.

Congenital heart defects (CHDs) are common human birth defects. Genetic mutations potentially cause the exhibition of various pathological phenotypes associated with CHDs, occurring alone or as part of certain syndromes. Zebrafish, a model organism with a strong molecular conservation similar to humans, is commonly used in studies on cardiovascular diseases owing to its advantageous features, such as a similarity to human electrophysiology, transparent embryos and larvae for observation, and suitability for forward and reverse genetics technology, to create various economical and easily controlled zebrafish CHD models. In this review, we outline the pros and cons of zebrafish CHD models created by genetic mutations associated with single defects and syndromes and the underlying pathogenic mechanism of CHDs discovered in these models. The challenges of zebrafish CHD models generated through gene editing are also discussed, since the cardiac phenotypes resulting from a single-candidate pathological gene mutation in zebrafish might not mirror the corresponding human phenotypes. The comprehensive review of these zebrafish CHD models will facilitate the understanding of the pathogenic mechanisms of CHDs and offer new opportunities for their treatments and intervention strategies.

Progress on the study of Popeye domain-containing 3 (POPDC3) in malignancies and striated muscle function and homeostasis.

The Popeye domain-containing protein 3 (POPDC3), a transmembrane protein with a unique cyclic adenosine monophosphate (cAMP) binding site, is widely expressed in mammalian tissues, with the highest levels of expression in skeletal muscle. POPDC3 plays a key role in many physiological and pathological processes and is considered a candidate biomarker and potential therapeutic target of cancer. In addition, POPDC3 gene variants have been associated with limb-girdle muscular dystrophy (LGMD) type 26. However, there are only a few studies on the biological role of POPDC3, interacting proteins, potential downstream targets, and regulated signaling pathways. Therefore, this review focuses on the structure of POPDC3 protein, interacting molecules, and the role and mechanism in cancer, and in cardiac and skeletal muscle, and to review the current research progress of POPDC3 and propose possible future study directions.

Aerobic Exercise Facilitates the Nuclear Translocation of SREBP2 by Activating AKT/SEC24D to Contribute Cholesterol Homeostasis for Improving Cognition in APP/PS1 Mice.

Impaired cholesterol synthesizing ability is considered a risk factor for the development of Alzheimer's disease (AD), as evidenced by reduced levels of key proteases in the brain that mediate cholesterol synthesis; however, cholesterol deposition has been found in neurons in tangles in the brains of AD patients. Although it has been shown that statins, which inhibit cholesterol synthesis, reduce the incidence of AD, this seems paradoxical for AD patients whose cholesterol synthesizing capacity is already impaired. In this study, we aimed to investigate the effects of aerobic exercise on cholesterol metabolism in the brains of APP/PS1 mice and to reveal the mechanisms by which aerobic exercise improves cognitive function in APP/PS1 mice. Our study demonstrates that the reduction of SEC24D protein, a component of coat protein complex II (COPII), is a key factor in the reduction of cholesterol synthesis in the brain of APP/PS1 mice. 12 weeks of aerobic exercise was able to promote the recovery of SEC24D protein levels in the brain through activation of protein kinase B (AKT), which in turn promoted the expression of mem-brane-bound sterol regulatory element-binding protein 2 (SREBP2) nuclear translocation and the expression of key proteases mediating cholesterol synthesis. Simultaneous aerobic exercise restored cholesterol transport capacity in the brain of APP/PS1 mice with the ability to efflux excess cholesterol from neurons and reduced neuronal lipid rafts, thereby reducing cleavage of the APP amyloid pathway. Our study emphasizes the potential of restoring intracerebral cholesterol homeostasis as a therapeutic strategy to alleviate cognitive impairment in AD patients.

Effects of Bushen Yiyuan recipe on testosterone synthesis in Leydig cells of rats with exercise-induced low serum testosterone levels.

CONTEXT: Bushen Yiyuan recipe (BYR) is an effective Chinese prescription with antifatigue and antioxidation effects. OBJECTIVE: The effects of BYR on testosterone synthesis in rat Leydig cells with exercise-induced low serum testosterone levels (EILST) are assessed. MATERIALS AND METHODS: Thirty-two Sprague-Dawley rats were chronically trained for 6 weeks to establish an EILST model. EILST rats were divided into model (physiological saline), EFE (700 mg/kg ethanol extract of Epimedii folium, the dried leaves of Epimedium brevicornu Maxim [Berberidaceae]), and BYR groups (350 and 700 mg/kg) for 6 weeks. Expression of HMG-CoA, LDL-R, SR-BI, STAR and CYP11A1 were quantified by RT qPCR and Western blots. RESULTS: Compared with the model group (115.52 ± 13.05 µg/dL; 67.83 ± 14.29; 0.32 ± 0.04; 0.33 ± 0.02; 0.38 ± 0.01), serum testosterone, testosterone/cortisol ratio, HMG-CoA, STAR and CYP11A1 relative protein expression significantly increased in low-dose BYR (210.60 ± 5.08 µg/dL; 119.38 ± 13.02; 0.47 ± 0.01; 0.46 ± 0.03; 0.46 ± 0.02), high-dose BYR (220.57 ± 14.71 µg/dL; 124.26 ± 14.79; 0.49 ± 0.02; 0.42 ± 0.03; 0.51 ± 0.02), and EFE groups (206.83 ± 5.54 µg/dL; 119.53 ± 25.04; 0.45 ± 0.02; 0.42 ± 0.02; 0.41 ± 0.02) (all p < 0.01, except for CYP11A1 in EFE group). HMG-CoA, STAR and CYP11A1 mRNA relative expression significantly increased in low-dose and high-dose BYR group compared to model group (all p < 0.01). CONCLUSIONS: BYR affects endogenous cholesterol synthesis and testosterone synthesis to prevent and treat EILST levels in rats. It can improve the body's sports ability.

Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 Signaling.

Non-alcoholic fatty liver disease (NAFLD) is a common disease that causes serious liver damage. Exercise is recognized as a non-pharmacological tool to improve the pathology of NAFLD. However, the antioxidative effects and mechanisms by which exercise ameliorates NAFLD remain unclear. The present study conducted exercise training on zebrafish during a 12-week high-fat feeding period to study the antioxidant effect of exercise on the liver. We found that swimming exercise decreased lipid accumulation and improved pathological changes in the liver of high-fat diet-fed zebrafish. Moreover, swimming alleviated NOX4-derived reactive oxygen species (ROS) overproduction and reduced methanedicarboxylic aldehyde (MDA) levels. We also examined the anti-apoptotic effects of swimming and found that it increased the expression of antiapoptotic factor bcl2 and decreased the expression of genes associated with apoptosis (caspase3, bax). Mechanistically, swimming intervention activated SIRT1/AMPK signaling-mediated lipid metabolism and inflammation as well as enhanced AKT and NRF2 activation and upregulated downstream antioxidant genes. In summary, exercise attenuates pathological changes in the liver induced by high-fat diets. The underlying mechanisms might be related to NRF2 and mediated by SIRT1/AMPK signaling.

Regular aerobic exercise-ameliorated troponin I carbonylation to mitigate aged rat soleus muscle functional recession.

NEW FINDINGS: What is the central question of this study? What is the biological role of carbonylation in muscle age-related functional decline and how might exercise affect the carbonylation process differently compared to habitual sedentary behaviour? What is the main finding and its importance? The carbonylation of troponin I (TNNI1), tropomyosin α-1 chain and α-actinin-1 demonstrated a relationship with muscle age-related functional decline. Exercise attenuated the decline by slowing the rate of carbonylation and promoting antioxidant reactions within the muscle. As exercise demonstrated the greatest effect on TNNI1, quantification of protein carbonyls in TNNI1 may be used as a potential biomarker of muscle age-related functional decline. ABSTRACT: This study investigated the biological role of carbonylation in muscle age-related functional decline and how regular aerobic exercise may affect the carbonylation process differently from habitual sedentary behaviour. Twenty-four healthy male Sprague-Dawley (SD) rats (mean age: 23 months) were randomly divided into an old-aged sedentary control group (O-SED) and an old-aged aerobic exercise group (O-EX). The O-EX group participated in regular aerobic exercise - treadmill running - with exercise intensity increased gradually from 50-55% to 65-70% of maximum oxygen consumption ( V̇O2max ) over 10 weeks. Rats' body weight, exercise behaviour index, morphology and oxidative stress were monitored. Avidin magnetic beads and electrospray ionization quadrupole time-of-flight mass spectrometry were used for gathering and separating carbonylated proteins while western blot tested for molecular targets. O-SED and O-EX rats both had 19 oxidative modification sites for protein carbonylation. In the O-SED group, 16 specific carbonylated proteins were identified, while 16 additional specific species were also found in the O-EX group, with all 28 species demonstrating oxidative modifications. The carbonylated proteins included troponin I (TNNI1; slow skeletal muscle), tropomyosin α1 and α-actinin 1. In particular, TNNI1 carbonylation modifications were found only in sedentary rats. Aerobic exercise increased TNNI1 and Ca2+ /calmodulin-dependent protein kinase IIα expression significantly. Observations suggested that quantification of TNNI1 carbonylation may be a potential biomarker of muscle age-related functional decline. Importantly, regular aerobic exercise appeared to have antioxidant effects in the muscle that reduced TNNI1 slow carbonylation and promoted Ca2+ /calmodulin-dependent protein kinase IIα (CAMK2) and TNNI1 expression for skeletal muscle contraction regulation, thus attenuating possible age-related skeletal muscle functional decline.

Proteomic Profile of Carbonylated Proteins Screen the Regulation of Calmodulin-Dependent Protein Kinases-AMPK-Beclin1 in Aerobic Exercise-Induced Autophagy in Middle-Aged Rat Hippocampus.

BACKGROUND: Carbonylation is an oxidative modification of the proteins and a marker of oxidative stress. The accumulation of toxic carbonylated proteins might be one of the onsets of pathogenesis in hippocampal aging or neurodegeneration. Enormous evidence indicates that regular aerobic exercise might alleviate the dysfunction of carbonylated proteins, but the adaptational mechanisms in response to exercise are unclear. OBJECTIVE: This study explored the carbonyl stress mechanism in the hippocampus using proteomics and the role of calmodulin-dependent protein kinases (CAMK)-AMP-activated protein kinase (AMPK)-Beclin1 signaling pathways in alleviating aging or improving function with regular aerobic exercise. METHODS: Twenty-four healthy 13-month-old male Sprague-Dawley rats (average 693.21 ± 68.85 g) were randomly divided into middle-aged sedentary control group (M-SED, n = 12) and middle-aged aerobic exercise runner group (M-EX, n = 12). The M-EX group participated in regular aerobic exercise - treadmill running - with exercise intensity increasing gradually from 50-55% to 65-70% of maximum oxygen consumption (V˙O2max) over 10 weeks. The targeted proteins of oxidative modification were profiled by avidin magnetic beads and electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF-MS). Western blots were used to test for molecular targets. RESULTS: Regular aerobic exercise restores the intersessional habituation and rescues the hippocampus morphological structure in middle-aged rats. -ESI-Q-TOF-MS screened 56 carbonylated proteins only found in M-SED and 16 carbonylated proteins only found in M-EX, indicating aerobic exercise decreased carbonyl stress. Intriguingly, Ca2+/CAMK II alpha (CAMKIIα) was carbonylated only in the M-SED group at the oxidative modification site of 4-hydroxynonenal adducts, while regular aerobic exercise alleviated CAMKIIα carbonylation. Regular aerobic exercise significantly increased the expression and phosphorylated, active levels of CAMKIIα and AMPKα1. It also upregulated the expression of Beclin1 and microtubule-associated protein1-light chain 3 in the hippocampus. CONCLUSION: Quantification of CAMKIIα carbonylation may be a potential biomarker of the hippocampal senescence. Additionally, regular aerobic exercise-induced autophagy via the activation of CAMK-AMPK-Beclin1 signaling pathway may mitigate the hippocampal neurodegeneration or pathological changes by alleviating protein carbonylation (carbonyl stress).

Calcineurin-NFAT Signaling and Neurotrophins Control Transformation of Myosin Heavy Chain Isoforms in Rat Soleus Muscle in Response to Aerobic Treadmill Training.

This study elucidated the role of CaN-NFAT signaling and neurotrophins on the transformation of myosin heavy chain isoforms in the rat soleus muscle fiber following aerobic exercise training. To do so, we examined the content and distribution of myosin heavy chain (MyHC) isoforms in the rat soleus muscle fiber, the activity of CaN and expression of NFATc1 in these fibers, and changes in the expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neutrophin-3 (NT-3) in the soleus and striatum following high-and medium-intensity aerobic treadmill training. Specific pathogen-free 2 month old male Sprague-Dawley (SD) rats were randomly divided into three groups: Control group (Con, n = 8), moderate-intensity aerobic exercise group (M-Ex, n = 8) and high-intensity aerobic exercise group (H-Ex, n = 8). We used ATPase staining to identify the muscle fiber type I and II, SDS-PAGE to separate and analyze the isoforms MyHCI, MyHCIIA, MyHCIIB and MyHCIIx, and performed western blots to determine the expression of NFATc1, NGF, BDNF and NT-3. CaN activity was measured using a colorimetric assay. In the soleus muscle, 8 weeks of moderate-intensity exercise can induce transformation of MyHC IIA and MyHC IIB to MyHC IIX and MyHC I (p < 0.01), while high-intensity treadmill exercise can induce transform MyHC IIx to MyHC IIB, MyHC IIA and MyHC I (p < 0.01). In comparison to the control group, CaN activity and NFATcl protein level were significantly increased in both the M-Ex and H-Ex groups (p < 0.05, p < 0.01), with a more pronounced upregulation in the M-Ex group (p < 0.05). Eight weeks of moderate- and high-intensity aerobic exercise induced the expression of NGF, BDNF and NT-3 in the soleus muscle and the striatum (p < 0.01), with the most significant increase in the H-Ex group (p < 0.01). In the rat soleus muscle, (1) CaN-NFATcl signaling contributes to the conversion of MyHC I isoform in response to moderate-intensity exercise; (2) Neurotrophins NGF, BDNF and NT-3 might play a role in the conversion of MyHC II isoform in response to high-intensity treadmill exercise. Key pointsEight weeks of moderate-intensity treadmill training induces the transformation MyHC IIA and MyHC IIB to MyHC IIX and MyHC I in the soleus muscles, while high-intensity exercise leads to transformation of MyHC IIX to MyHC IIA, MyHC IIB and MyHC I.MyHC I conversion in response to moderate-intensity aerobic exercise is mediated by calcineurin-NFATcl signaling.Eight weeks of moderate- and high-ntensity aerobic exercise induces the expression of NGF, BDNF and NT-3 in expression noted in rats subjected to high-intensity training. NGF and NT-3 expression in the striatum is lower than in the soleus muscle, while BDNF levels are similar. Neurotrophins may be involved in mediating MyHC II conversion in response to high-intensity aerobic exercise.

New insights into the function of the NLRP3 inflammasome in sarcopenia: mechanism and therapeutic strategies.

Sarcopenia is one of the most common skeletal muscle disorders and is characterized by infirmity and disability. While extensive research has focused on elucidating the mechanisms underlying the progression of sarcopenia, further comprehensive insights into its pathogenesis are necessary to identify new preventive and therapeutic approaches. The involvement of inflammasomes in sarcopenia is widely recognized, with particular emphasis on the NLRP3 (NLR family pyrin domain containing 3) inflammasome. In this review, we aim to elucidate the underlying mechanisms of the NLRP3 inflammasome and its relevance in sarcopenia of various etiologies. Furthermore, we highlight interventions targeting the NLRP3 inflammasome in the context of sarcopenia and discuss the current limitations of our knowledge in this area.

A Systematic review of the factors that affect soccer players' short-passing ability-based on the Loughborough Soccer Passing Test.

OBJECTIVE: This study synthesizes evidence from the Loughborough Passing Test to evaluate the short-passing ability of soccer players and summarizes the reported variables that affect this ability to provide support for the development and improvement of short-passing abilities in soccer players. METHODS: In this systematic review using the PRISMA guidelines, a comprehensive search was conducted in Web of Science, PubMed, and EBSCOhost from inception to July 2023 to identify relevant articles from the accessible literature. Only studies that used the Loughborough test to assess athletes' short-passing ability were included. The quality of the included studies was independently assessed by two reviewers using the PEDro scale, and two authors independently completed the data extraction. RESULTS: Based on the type of intervention or influencing factor, ten studies investigated training, nine studies investigated fatigue, nine studies investigated supplement intake, and five studies investigated other factors. CONCLUSION: Evidence indicates that fitness training, small-sided games training, and warm-up training have positive effects on athletes' short-passing ability, high-intensity special-position training and water intake have no discernible impact, mental and muscular exhaustion have a significantly negative effect, and the effect of nutritional ergogenic aid intake is not yet clear. Future research should examine more elements that can affect soccer players' short-passing ability. TRIAL REGISTRATION: https://inplasy.com/ ., identifier: INPLASY20237.

Treadmill exercise can regulate the redox balance in the livers of APP/PS1 mice and reduce LPS accumulation in their brains through the gut-liver-kupffer cell axis.

A growing body of clinical data has shown that patients with Alzheimer's disease (AD) have symptoms such as liver dysfunction and microbial-gut-brain axis dysfunction in addition to brain pathology, presenting a systemic multisystemic pathogenesis. Considering the systemic benefits of exercise, here, we first observed the effects of long-term treadmill exercise on liver injuries in APP/PS1 transgenic AD mice and explored the potential mechanisms of the gut-liver-brain axis's role in mediating exercise's ability to reduce bacterial lipopolysaccharide (LPS) pathology in the brain. The results showed that the livers of the AD mice were in states of oxidative stress, while the mice after long-term treadmill exercise showed alleviation of their oxidative stress, their intestinal barriers were protected, and the ability of their Kupffer cells to hydrolyze LPS was improved, in addition to the accumulation of LPS in their brains being reduced. Notably, the livers of the AD mice were in immunosuppressed states, with lower pro-oxidative and antioxidative levels than the livers of the wild-type mice, while exercise increased both their oxidative and antioxidative levels. These results suggest that long-term exercise modulates hepatic redox homeostasis in AD mice, attenuates oxidative damage, and reduces the accumulation of LPS in the brain through the combined action of the intestine-liver-Kupffer cells.

Psychometric properties of the Sport Anxiety Scale-2 for Chinese adolescent athletes taking the National Sports College Entrance Examination.

Background: This study aims to evaluate the psychometric properties of the Sport Anxiety Scale-2 (SAS-2) in Chinese adolescent sports exam candidates. Methods: One day before the National Sports College Entrance Examination, 965 Chinese athletes rated the Chinese-language SAS-2. Confirmatory factor analysis was performed to test the three-factor structure. Factorial invariance was tested by comparing the configural invariance model to three more constrained models. Construct validity and reliability were determined. Results: Fit indices meet the critical values: CFI = 0.953, TLI = 0.943, RMSEA = 0.048 [90% CI, 0.041-0.054], and SRMR = 0.042. All path factor loadings exceed 0.5. The changes in CFI and RMSEA across the configural, metric, scalar, and uniqueness invariance are within the critical values, demonstrating strict measurement invariance across gender, years of training, and type of sports. The average variance extracted of the worry sub-scale is above the cutoff criteria, and McDonald's omega coefficients are over 0.70. Significant correlations exist between the SAS-2, SCAT, and CSAI-2. Factor correlations are all below 0.8. The measurement also distinguishes the known gender effect, with females showing a probability of 58.6% higher anxiety levels. The intraclass correlation coefficient ranges from 0.706 to 0.801. Conclusion: This study validated the Chinese-language SAS-2 in measuring competitive anxiety among Chinese adolescent athletes taking the National Sports College Entrance Examination. The development of the scale's applicability in China is discussed.

Heme oxygenase-1: A potential therapeutic target for improving skeletal muscle atrophy.

Skeletal muscle atrophy is a common muscle disease that is directly caused by an imbalance in protein synthesis and degradation. At the histological level, it is mainly characterized by a reduction in muscle mass and fiber cross-sectional area (CSA). Patients with skeletal muscle atrophy present with reduced motor ability, easy fatigue, and poor life quality. Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes the degradation of heme and has attracted much attention for its anti-oxidation effects. In addition, there is growing evidence that HO-1 plays an important role in anti-inflammatory, anti-apoptosis, pro-angiogenesis, and maintaining skeletal muscle homeostasis, making it a potential therapeutic target for improving skeletal muscle atrophy. Here, we review the pathogenesis of skeletal muscle atrophy, the biology of HO-1 and its regulation, and the biological function of HO-1 in skeletal muscle homeostasis, with a specific focus on the role of HO-1 in skeletal muscle atrophy, aiming to observe the therapeutic potential of HO-1 for skeletal muscle atrophy.

Regular exercise attenuates alcoholic myopathy in zebrafish by modulating mitochondrial homeostasis.

Alcoholic myopathy is caused by chronic consumption of alcohol (ethanol) and is characterized by weakness and atrophy of skeletal muscle. Regular exercise is one of the important ways to prevent or alleviate skeletal muscle myopathy. However, the beneficial effects and the exact mechanisms underlying regular exercise on alcohol myopathy remain unclear. In this study, a model of alcoholic myopathy was established using zebrafish soaked in 0.5% ethanol. Additionally, these zebrafish were intervened to swim for 8 weeks at an exercise intensity of 30% of the absolute critical swimming speed (Ucrit), aiming to explore the beneficial effects and underlying mechanisms of regular exercise on alcoholic myopathy. This study found that regular exercise inhibited protein degradation, improved locomotion ability, and increased muscle fiber cross-sectional area (CSA) in ethanol-treated zebrafish. In addition, regular exercise increases the functional activity of mitochondrial respiratory chain (MRC) complexes and upregulates the expression levels of MRC complexes. Regular exercise can also improve oxidative stress and mitochondrial dynamics in zebrafish skeletal muscle induced by ethanol. Additionally, regular exercise can activate mitochondrial biogenesis and inhibit mitochondrial unfolded protein response (UPRmt). Together, our results suggest regular exercise is an effective intervention strategy to improve mitochondrial homeostasis to attenuate alcoholic myopathy.

Exercise intervention improves mitochondrial quality in non-alcoholic fatty liver disease zebrafish.

Introduction: Recent reports indicate that mitochondrial quality decreases during non-alcoholic fatty liver disease (NAFLD) progression, and targeting the mitochondria may be a possible treatment for NAFLD. Exercise can effectively slow NAFLD progression or treat NAFLD. However, the effect of exercise on mitochondrial quality in NAFLD has not yet been established. Methods: In the present study, we fed zebrafish a high-fat diet to model NAFLD, and subjected the zebrafish to swimming exercise. Results: After 12 weeks, swimming exercise significantly reduced high-fat diet-induced liver injury, and reduced inflammation and fibrosis markers. Swimming exercise improved mitochondrial morphology and dynamics, inducing upregulation of optic atrophy 1(OPA1), dynamin related protein 1 (DRP1), and mitofusin 2 (MFN2) protein expression. Swimming exercise also activated mitochondrial biogenesis via the sirtuin 1 (SIRT1)/ AMP-activated protein kinase (AMPK)/ PPARgamma coactivator 1 alpha (PGC1α) pathway, and improved the mRNA expression of genes related to mitochondrial fatty acid oxidation and oxidative phosphorylation. Furthermore, we find that mitophagy was suppressed in NAFLD zebrafish liver with the decreased numbers of mitophagosomes, the inhibition of PTEN-induced kinase 1 (PINK1) - parkin RBR E3 ubiquitin protein ligase (PARKIN) pathway and upregulation of sequestosome 1 (P62) expression. Notably, swimming exercise partially recovered number of mitophagosomes, which was associated with upregulated PARKIN expression and decreased p62 expression. Discussion: These results demonstrate that swimming exercise could alleviate the effects of NAFLD on the mitochondria, suggesting that exercise may be beneficial for treating NAFLD.

Aerobic exercise enhances mitochondrial homeostasis to counteract D-galactose-induced sarcopenia in zebrafish.

Sarcopenia is a common skeletal muscle degenerative disease characterized by decreased skeletal muscle mass and mitochondrial dysfunction that involves microRNAs (miR) as regulatory factors in various pathways. Exercise reduces age-related oxidative damage and chronic inflammation and increases autophagy, among others. Moreover, whether aerobic exercise can regulate mitochondrial homeostasis by modulating the miR-128/insulin-like growth factor-1 (IGF-1) signaling pathway and can improve sarcopenia requires further investigation. Interestingly, zebrafish have been used as a model for aging research for over a decade due to their many outstanding advantages. Therefore, we established a model of zebrafish sarcopenia using d-galactose immersion and observed substantial changes, including reduced skeletal muscle cross-sectional area, increased tissue fibrosis, decreased motility, increased skeletal muscle reactive oxygen species, and notable alterations in mitochondrial morphology and function. We found that miR-128 expression was considerably upregulated, where as Igf1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were significantly downregulated; moreover, mitochondrial homeostasis was reduced. Four weeks of aerobic exercise delayed sarcopenia progression and prevented the disruption of mitochondrial function and homeostasis. The genes related to atrophy and miR-128 were downregulated, Igf1 expression was considerably upregulated, and the phosphorylation levels of Pi3k, Akt, and Foxo3a were upregulated. Furthermore, mitochondrial respiration and homeostasis were enhanced. In conclusion, aerobic exercise improved skeletal muscle quality and function via the miR-128/IGF-1 signaling pathway, consequently ameliorating mitochondrial homeostasis in aging skeletal muscle.

Alcohol Induces Zebrafish Skeletal Muscle Atrophy through HMGB1/TLR4/NF-κB Signaling.

Excessive alcohol consumption can cause alcoholic myopathy, but the molecular mechanism is still unclear. In this study, zebrafish were exposed to 0.5% alcohol for eight weeks to investigate the effect of alcohol on skeletal muscle and its molecular mechanism. The results showed that the body length, body weight, cross-sectional area of the skeletal muscle fibers, Ucrit, and MO2max of the zebrafish were significantly decreased after alcohol exposure. The expression of markers of skeletal muscle atrophy and autophagy was increased, and the expression of P62 was significantly reduced. The content of ROS, the mRNA expression of sod1 and sod2, and the protein expression of Nox2 were significantly increased. In addition, we found that the inflammatory factors Il1ß and Tnfα were significantly enriched in skeletal muscle, and the expression of the HMGB1/TLR4/NF-κB signaling axis was also significantly increased. In summary, in this study, we established a zebrafish model of alcohol-induced skeletal muscle atrophy and further elucidated its pathogenesis.

A High-Fat Diet Induces Muscle Mitochondrial Dysfunction and Impairs Swimming Capacity in Zebrafish: A New Model of Sarcopenic Obesity.

Obesity is a highly prevalent disease that can induce metabolic syndrome and is associated with a greater risk of muscular atrophy. Mitochondria play central roles in regulating the physiological metabolism of skeletal muscle; however, whether a decreased mitochondrial function is associated with impaired muscle function is unclear. In this study, we evaluated the effects of a high-fat diet on muscle mitochondrial function in a zebrafish model of sarcopenic obesity (SOB). In SOB zebrafish, a significant decrease in exercise capacity and skeletal muscle fiber cross-sectional area was detected, accompanied by high expression of the atrophy-related markers Atrogin-1 and muscle RING-finger protein-1. Zebrafish with SOB exhibited inhibition of mitochondrial biogenesis and fatty acid oxidation as well as disruption of mitochondrial fusion and fission in atrophic muscle. Thus, our findings showed that muscle atrophy was associated with SOB-induced mitochondrial dysfunction. Overall, these results showed that the SOB zebrafish model established in this study may provide new insights into the development of therapeutic strategies to manage mitochondria-related muscular atrophy.

Treadmill Exercise Modulates Intestinal Microbes and Suppresses LPS Displacement to Alleviate Neuroinflammation in the Brains of APP/PS1 Mice.

Neuroinflammation occurs throughout the pathogenesis of Alzheimer's disease (AD). Here, we investigated the effects of treadmill exercise on neuroinflammation in APP/PS1 transgenic AD mice and the potential involvement of microbe-gut-brain axis (MGB) mechanisms based on growing evidence that AD's pathogenesis is correlated with a deterioration in the function of gut microbiota. APP/PS1 transgenic AD mice were subjected to 12 weeks of treadmill exercise, followed by spatial memory tests. After the behavioral study, the amyloid (Aß) pathology, gut microbes and metabolites, bacterial lipopolysaccharide (LPS) displacement, and degree of neuroinflammation were analyzed. We found that this strategy of exercise enriched gut microbial diversity and alleviated neuroinflammation in the brain. Notably, exercise led to reductions in pathogenic bacteria such as intestinal Allobaculum, increases in probiotic bacteria such as Akkermansia, increased levels of intestine-brain barrier proteins, and attenuated LPS displacement. These results suggest that prolonged exercise can effectively modulate gut microbes and the intestinal barrier and thereby reduce LPS displacement and ultimately alleviate AD-related neuroinflammation.