Background:Insufficient physical activity and prolonged sedentary behavior have emerged as major global public health challenges.Short bouts(≤10 min)of accumulated exercise(SBAE)throughout the day may be a promising ...Background:Insufficient physical activity and prolonged sedentary behavior have emerged as major global public health challenges.Short bouts(≤10 min)of accumulated exercise(SBAE)throughout the day may be a promising strategy to mitigate the adverse effects of prolonged sitting and promote physical activity,ultimately promoting overall health.However,previous ambiguity in defining this concept has resulted in a fragmented and inconsistent evidence base,impeding practical applications,the development of guidelines,and policymaking.The purpose of this study is to establish an operational definition of SBAE by synthesizing systematic reviews and research trials alongside an expert consensus.Additionally,it seeks to evaluate acute and long-term efficacy and feasibility,providing evidence-based recommendations for practice and future research directions.Methods:A literature search was performed across PubMed and Web of Science,followed by systematic screening and summarization of eligible studies based on predefined inclusion criteria.Inclusion criteria encompassed various modes/types of SBAE(bouts lasting≤10 min,performed multiple times daily with≥30 min intervals);both aerobic and resistance exercise were considered.Relevant systematic reviews and research trials were included.Methodological quality,risk of bias,and evidence certainty were assessed.Expert consensus was obtained through a survey to evaluate recommendations and agreement levels on findings.Results:After analyzing 27 systematic reviews,135 research studies,and an expert consensus involving 48 researchers from 11 countries,SBAE is defined as any exercise mode of activity,regardless of intensity,that is accumulated in either continuous or intermittent bouts lasting≤10 min per session(including multiple intermittent sets)that are performed multiple times(≥2 sessions/day)per day,with intervals of≥30 min between bouts or otherwise sufficient time for recovery.When used to interrupt prolonged periods of sedentary time,SBAE mitigates the acute adverse effects of sedentary behavior on more than 10 clinical biomarkers of endocrine,cardiovascular,and brain health/function among adults of diverse ages and conditions.Moreover,SBAE was superior for improving acute glycemic control compared to a single continuous exercise session.As a long-term intervention(average of 11 weeks),SBAE can improve over 20 health outcomes,including peak oxygen uptake,resting blood pressure,and metabolic health.Additionally,SBAE might be more effective than continuous exercise for improving longer-term glycemic control and body composition.Long-term completion rates for SBAE interventions are generally high(95%),with low dropout rates(12%)and high adherence rates even without supervision(85%),and its safety has been preliminarily validated.Conclusion:An operational definition of SBAE is provided along with its classification and acute and long-term efficacy.Practical exercise prescription recommendations and evidence-based strategies for various populations and contexts are provided.Future research should focus on generating high-quality evidence for SBAE in 5 key areas:quantification and monitoring,population-specific responses,optimization of exercise prescriptions,intervention efficacy,and practical implementation.Additionally,addressing policy,environmental,and promotional barriers is crucial for transitioning from expert consensus to public consensus,and for facilitating the application of this strategy in real-world environments.展开更多
This study aims to explore the impact of fatigue induced by different limb exercises on cerebral cortical oxygenation levels and functional connectivity strength using functional near-infrared spectroscopy(fNIRS).Fati...This study aims to explore the impact of fatigue induced by different limb exercises on cerebral cortical oxygenation levels and functional connectivity strength using functional near-infrared spectroscopy(fNIRS).Fatigue was induced using an upper limb ergometer or a lower limb ergometer,with the load increasing gradually each minute.fNIRS covering the prefrontal cortex and motor cortex were used to collect data during the resting state,both before and after fatigue induction.A two-way ANOVA was conducted to examine differences in oxyhemoglobin(HbO_(2))and functional connectivity before and after fatigue induction in both groups,with the significance level set at 0.05.Exercise-induced fatigue in both the upper and lower limbs leads to a significant decrease in cerebral cortical oxygenation levels.Upper limb fatigue leads to a significant reduction in functional connectivity,there were significant decreases in connectivity within the motor cortex,between the motor cortex and frontal regions,and between the right ventrolateral prefrontal cortex and other frontal regions.Conversely,no significant changes were observed before and after lower limb fatigue.Future studies should focus on examining the extent to which how changes in the cerebral cortex,induced by exercise fatigue,are linked to exercise-and/or performance-related outcomes.展开更多
Parkinson's disease(PD)is the second most common neurodegenerative disease that affects movement and cognitive function,resulting from the loss of the neurotransmitter dopamine due to the death of dopaminergic neu...Parkinson's disease(PD)is the second most common neurodegenerative disease that affects movement and cognitive function,resulting from the loss of the neurotransmitter dopamine due to the death of dopaminergic neurons.It affects nearly one million people in the United States and 8.5 million worldwide.While there are some pharmacological and surgical options available,they only provide symptomatic relief,as there is currently no cure for PD.In contrast,exercise training,a non-pharmacological intervention,has emerged as a powerful strategy to enhance the psychological,cognitive,and physiological(motor)impairments associated with PD.Given that the beneficial effects of exercise differ based on the intensity and type of training,gaining a thorough understanding of the molecular mechanisms underlying exercise-induced protection is crucial for developing innovative therapies that improve the quality of life for PD patients around the globe.This review discusses PD pathogenesis and pathophysiology and provides recent clinical evidence of neuroprotective benefits from various exercise modalities and intensity.Furthermore,the molecular mechanisms of exercise in PD pathogenesis(e.g.,modulations on neurotrophic factors,oxidative stress,mitochondria dysfunction,endoplasmic reticulum stress,and autophagy)will be emphasized.展开更多
Background: We monitored changes in salivary creatine pre-and post-high-intensity exercise in young adults while also investigating the potential correlation between salivary and serum creatine levels.Method: Saliva a...Background: We monitored changes in salivary creatine pre-and post-high-intensity exercise in young adults while also investigating the potential correlation between salivary and serum creatine levels.Method: Saliva and serum samples were collected before and immediately after an incremental running-toexhaustion treadmill test in fifteen young adults(mean age [23.9 ± 2.9] years, eight females), with samples analyzed for guanidinoacetic acid, creatine, and creatinine using a liquid chromatography–tandem mass spectrometry method.Results: Following exercise, there was a substantial elevation in salivary creatine levels from(17.5 ± 14.2)μmol·L^(-1) to(43.6 ± 30.4) μmol·L^(-1)(p < 0.001), coupled with a significant increase in salivary creatinine from(11.3 ± 5.8) μmol·L^(-1) to(17.0 ± 9.3) μmol·L^(-1)(p = 0.04). In contrast, serum creatine levels were unaffected by exercise(p = 0.80), while creatinine levels exhibited a strong tendency to decrease post-exercise(from [81.8 ±17.5] μmol·L^(-1) to [73.1 ± 11.6] μmol·L^(-1);p = 0.06). A comparison of the slopes of the two regression lines(saliva vs. serum) revealed significant differences for both creatine(p = 0.01) and creatinine(p = 0.03).Conclusions: The above findings suggest a potential difference in the dynamics of creatine metabolites in these two bodily fluids, both pre and post-exercise.展开更多
Overweight and obesity are significant public health concerns worldwide due to their association with many chronic health conditions.This has resulted in the development of various interventions focused on weight loss...Overweight and obesity are significant public health concerns worldwide due to their association with many chronic health conditions.This has resulted in the development of various interventions focused on weight loss to reduce the associated health burden.Physical activity is an important lifestyle behavior associated with enhanced health.Evidence supports that many of the benefits of physical activity are realized independent of initial weight status or whether weight loss is achieved,with some benefits additive to what is achieved with weight loss alone.These benefits include enhanced cardiometabolic,brain,cognitive and psychological health,and others.Moreover,in adults with overweight or obesity,physical activity has independent effects on cardiorespiratory fitness,muscular strength,physical function,and mobility.There are also benefits to body composition,with physical activity improving the quality of key tissues,such as skeletal muscle,which may not occur with diet-induced weight loss.Therefore,physical activity is an important public health target for adults with overweight or obesity to provide a wide range of health benefits that extend beyond those of weight loss alone.However,physical activity recommendations and programming efforts should consider the unique characteristics of adults with overweight or obesity to be most effective,and should support a focus on mobility,physical function,and other health outcomes.展开更多
Exercise produces a decrease in pain sensitivity via an effect called exercise-induced hypoalgesia(EIH).Transcranial direct current stimulation(tDCS),acting on similar analgesic mechanisms as EIH,represents a potentia...Exercise produces a decrease in pain sensitivity via an effect called exercise-induced hypoalgesia(EIH).Transcranial direct current stimulation(tDCS),acting on similar analgesic mechanisms as EIH,represents a potential complementary intervention that may amplify the effects of exercise on pain.This study aimed to explore if anodal tDCS could enhance the effect of exercise on pain compared to exercise alone.A total of 35 healthy participants aged 19–37 years completed a familiarisation session followed by two separate sessions where active and sham tDCS was applied in a randomised cross-over design.The familiarisation session involved familiarisation to the pain assessment and exercise tasks,while the subsequent tDCS sessions involved pain sensitivity assessment,exercise and either anodal tDCS or sham tDCS.tDCS doses were applied at 2 mA over the primary motor cortex for 10 min,with the reference electrode placed over the contralateral supraorbital area.The exercise task involved a sustained isometric grip strength contraction at 35%of maximal voluntary contraction(MVC)until volitional exhaustion.Pain sensitivity was evaluated as pressure pain threshold before tDCS,after tDCS,and after exercise.Across both tDCS conditions,pain threshold was higher after exercise when compared to pre-and post-tDCS measurement.This increase in pain threshold did not differ between active and sham tDCS conditions.Our findings suggest that the hypoalgesic effects of active anodal tDCS over the motor cortex prior to exercise are no greater than the effects of sham tDCS prior to exercise.展开更多
Advances in skeletal muscle omics has expanded our understanding of exercise-induced adaptations at the molecular level.Over the past 2 decades,transcriptome studies in muscle have detailed acute and chronic responses...Advances in skeletal muscle omics has expanded our understanding of exercise-induced adaptations at the molecular level.Over the past 2 decades,transcriptome studies in muscle have detailed acute and chronic responses to resistance,endurance,and concurrent exercise,focusing on variables such as training status,nutrition,age,sex,and metabolic health profile.Multi-omics approaches,such as the integration of transcriptomic and epigenetic data,along with emerging ribosomal RNA sequencing advancements,have further provided insights into how skeletal muscle adapts to exercise across the lifespan.Downstream of the transcriptome,proteomic and phosphoproteomic studies have identified novel regulators of exercise adaptations,while single-cell/nucleus and spatial sequencing technologies promise to evolve our understanding of cellular specialization and communication in and around skeletal muscle cells.This narrative review highlights(a)the historical foundations of exercise omics in skeletal muscle,(b)current research at 3 layers of the omics cascade(DNA,RNA,and protein),and(c)applications of single-cell omics and spatial sequencing technologies to study skeletal muscle adaptation to exercise.Further elaboration of muscle's global molecular footprint using multi-omics methods will help researchers and practitioners develop more effective and targeted approaches to improve skeletal muscle health as well as athletic performance.展开更多
The purpose is to explore the effects of Exercise rehabilitation(ER)on bone mineral density(BMD)of the knee,muscle strength(MS),and physical function(PF)after ACL rupture.Finally,A total of 58 patients were randomized...The purpose is to explore the effects of Exercise rehabilitation(ER)on bone mineral density(BMD)of the knee,muscle strength(MS),and physical function(PF)after ACL rupture.Finally,A total of 58 patients were randomized into 2 groups(Control Group[CON]:conventional treatment,male=16,female=13,age=[31.63±8.01]years;Exercise rehabilitation group[ER]:6-week ER on CON basis,male=17,female=12,age=[31.26±7.07]years).At baseline and 6 weeks,the knee BMD was measured using DEXA,MS and PF measures were recorded by isokinetic strength test,IKDC,Lysholm,and VAS score.T-tests,analysis of variance(ANOVA),and Mann-Whitney tests were used for comparisons.The BMD outcomes:after a 6-week period,the BMD of the CON([1.47±0.24]g·cm^(-2))was significantly lower than that of the ER([1.65±0.37]g·cm^(-2))at lateral condyle of femur(LCF)(p=0.041).MS outcomes:at 6 weeks,the relative peak torque(RPT)of the quadriceps and hamstrings during concentric contractions in ER group were significantly higher than that in CON group(p<0.001,p=0.017).Similarly,during eccentric contractions in ER group,the RPT of the quadriceps and the H/Q ratio revealed significant variations from the CON group(p=0.033,p=0.043).PF outcomes:the IKDC,Lysholm,and VAS scores of the ER group were significantly improved compared to the CON group(p<0.001,p<0.001,p=0.002).The conclusion is that 6 weeks of ER intervention for patients with ACL rupture can effectively delay the decline of BMD in the LCF of the knee joint,and enhance the restoration of MS and PF.This provides guidance for clinical rehabilitation.展开更多
Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitatio...Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.展开更多
We read with great interest the recent article by Valenzuela et al.1titled“Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability:Insights from McArdle disease”published in the Journ...We read with great interest the recent article by Valenzuela et al.1titled“Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability:Insights from McArdle disease”published in the Journal of Sport and Health Science The study's exploration of the effects of varying carbohydrate(CHO)doses on exercise capacity in Mc Ardle disease,a condition characterized by complete muscle glycogen unavailability,is a significant contribution to the field of sports science and metabolic disorders.展开更多
Objectives:Aerobic exercise training can increase skeletal muscle mitochondrial content.Supine exercise training with legs above the heart potentially augments these increases.However,the impact of supine exercise tra...Objectives:Aerobic exercise training can increase skeletal muscle mitochondrial content.Supine exercise training with legs above the heart potentially augments these increases.However,the impact of supine exercise training on mitochondrial biogenesis and cardiovascular adaptations remains unclear.Methods:In this single-centred,randomized,parallel arm trial,19 recreationally active individuals underwent seven sessions of either supine with legs up(SUP;n=9,6 females)or upright with legs down(UP;n=10,7 females)aerobic training on a recumbent bike at 71±7%and 71±2%of peak work rate(WRpeak),respectively.The study aimed to test the effects of training with decreased muscle oxygenation on indices of muscle mitochondrial remodelling.Secondary outcomes included exercise performance,muscle oxygenation,and cardiovascular responses.Results:Secondary outcomes revealed significant interaction effects for time to fatigue(TTF)and WRpeak in the SUP group during supine testing,suggesting enhanced exercise tolerance and performance.No between group interaction effects were observed for upright testing.No clear effects on mitochondrial biogenesis were observed based on expression of mitochondrial protein subunits and transcriptional regulators.Acutely,HRpeak was lower during the SUP Test compared to the UP Test.No central cardiovascular adaptations were observed following training.Conclusions:Our exploratory analyses showed that supine aerobic training more effectively improves supine exercise tolerance and performance compared with upright training,despite no differences in measured proteins related to mitochondrial biogenesis.Further research is needed to elucidate the mechanisms underlying these postural-specific training effects.Registration:clinicaltrials.gov:NCT04151095.展开更多
Background While Nordic hamstring exercise(NHE)training has been shown to reduce hamstring strains,the muscle-specific adaptations to NHE across the 4 hamstrings remain unclear.This study investigates architectural an...Background While Nordic hamstring exercise(NHE)training has been shown to reduce hamstring strains,the muscle-specific adaptations to NHE across the 4 hamstrings remain unclear.This study investigates architectural and microstructural adaptations of the biceps femoris short head(BFsh),biceps femoris long head(BFlh),semitendinosus(ST),and semimembranosus(SM)in response to an NHE intervention.Methods Eleven subjects completed 9 weeks of supervised NHE training followed by 3 weeks of detraining.Magnetic resonance imaging was performed at pre-training,post-training,and detraining to assess architectural(volume,fiber tract length,and fiber tract angle)and microstructural(axial(AD),mean(MD),radial(RD)diffusivities,and fractional anisotropy(FA))parameters of the 4 hamstrings.Results NHE training induced significant but non-uniform hamstring muscle hypertrophy(BFsh:22%,BFlh:9%,ST:26%,SM:6%)and fiber tract length increase(BFsh:11%,BFlh:7%,ST:18%,SM:10%).AD(5%),MD(4%),and RD(5%)showed significant increases,but fiber tract angle and FA remained unchanged.After detraining,only ST showed a significant reduction(8%)in volume,which remained higher than the pre-training value.While fiber tract lengths returned to baseline,AD,MD,and RD remained higher than pre-training levels for all hamstrings.Conclusion The 9-week NHE training substantially increased hamstring muscle volume with greater hypertrophy in ST and BFsh.Hypertrophy was accompanied by increases in fiber tract lengths and cross-sections(increased RD).After 3 weeks of detraining,fiber tract length gains across all hamstrings declined,emphasizing the importance of sustained training to maintain all the protective adaptations.展开更多
It is well known that appropriate aerobic exercise can effectively alleviate fatty liver and enhance brain function.The concept of multi-organ crosstalk coordinating disease progression has become the current research...It is well known that appropriate aerobic exercise can effectively alleviate fatty liver and enhance brain function.The concept of multi-organ crosstalk coordinating disease progression has become the current research hot topic.However,there remains an urgent need to elucidate its specific mechanisms.This study aimed to explore the impact of a high-fat diet(HFD)on liver health and cognitive function,and to further uncover the regulatory effect of aerobic exercise by liver-specific activating transcription factor 3(Atf3)knockout(ATF3cKO)mice in a“liver-brain”axis mode.The 5-week-old C57BL/6 and ATF3cKO mice were fed with HFD for 32 weeks,and sequentially subjected to aerobic exercise intervention at the 20th week for another 12 consecutive weeks.Meanwhile,C57BL/6 mice were provided with a normal diet as the control group.The functional parameters of liver and brain of all mice were assessed.Cognitive capacity of all mice was assessed by the Morris water maze(MWM).Inflammatory factors in the serum and brain of mice were quantified using enzyme-linked immunosorbent assay(ELISA),and the expression of inflammasomes was detected by immunohistochemistry(IHC).Additionally,the activation of nuclear factor-κB(NF-κB)and phosphoinositide 3-kinase(PI3K)signal pathways was analyzed by Western blotting.In this study,HFD impaired hepatic and brain functions,while aerobic exercise and liver-specific Atf3 knockout suppressed inflammatory factors in the peripheral circulation through hepatoprotective mechanisms,thereby attenuating cerebral inflammation and preserving neurological integrity,as well as mitigating HFD-induced cognitive decline.展开更多
Nutrigenomics is an emerging research field to investigate the interactions between food components and genes and elucidate their impacts on health and diseases.Exercise,another critical factor influencing human healt...Nutrigenomics is an emerging research field to investigate the interactions between food components and genes and elucidate their impacts on health and diseases.Exercise,another critical factor influencing human health,is intricately linked with nutrition and genetics,and is influenced by a combination of genetic background,lifestyle choice,and environmental factors.The high-throughput sequencing technologies and advanced bioinformatic tools have offered researchers to delve deeper into how individual genetic expression responses to exercise and how dietary interventions can enhance exercise performance and recovery through the gene expression changes and modifications.Among these mechanisms,gene expression emerges as the primary focus,highlighting its role in linking nutrients and exercise to metabolic pathways,muscle synthesis,and inflammation.While epigenetic modifications are briefly considered,the emphasis remains on how direct and indirect influences on gene expression drive physiological adaptations.Herein,the article reviews recent advancements in nutrigenomics within the context of exercise science,exploring gene-regulating mechanisms affected by specific nutrients and dietary patterns on exercise capacity,muscle synthesis,and damage repair.It also outlines the potential applications of personalized nutrition plans in athletic training and general fitness.In addition,this article addresses current challenges and potential issues in the practical implementation of nutrigenomics in exercise-induced health promotion.Future studies should emphasize interdisciplinary collaboration to unravel the intricate gene-nutrition-exercise interaction networks,thereby providing a solid theoretical foundation and technological support for the advancement of precision exercise nutrition.展开更多
L-Theanine(LTA)is a non-protein amino acid mainly found in tea plants with many beneficial effects.Exercise exerts a wide range of benefits in metabolic health.Here,we show that exercise or gastric lavage intervention...L-Theanine(LTA)is a non-protein amino acid mainly found in tea plants with many beneficial effects.Exercise exerts a wide range of benefits in metabolic health.Here,we show that exercise or gastric lavage intervention on mice with LTA improves diet-induced nonalcoholic steatohepatitis(NASH)in mice.Meanwhile,combinatory therapy shows that exercise and LTA synergistically improve obesity-related metabolic disorders and NASH phenotypes,including hepatic steatosis,inflammation,cell death and oxidative stress.In vivo studies indicate that LTA inhibits free fatty acid(FFA)-induced hepatocyte injury,including steatosis,oxidative stress and apoptosis.Knockdown of Nrf2 blunts the role of LTA in inhibiting FFA-induced hepatocyte oxidative stress and dysfunction.Mechanistically,LTA increases theα-ketoglutarate(α-KG)level in hepatocytes,which increases the transcription of Nrf2 by inducing active DNA demethylation on its promoter.Moreover,LTA promote the aboveα-KG/Nrf2 axis in synergy with exercise,thereby more efficiently inhibiting hepatic oxidative stress and ameliorating diet-induced NASH in mice.Our results suggest that,through promoting theα-KG/Nrf2 axis-mediated anti-oxidative pathway,the combination of LTA and exercise may provide an effective measure for the prevention and control of NASH.展开更多
Background Regular exercise training provides significant health benefits among cancer survivors and is associated with lower breast cancer mortality and reduced risk of recurrence.Both exercise-induced factors secret...Background Regular exercise training provides significant health benefits among cancer survivors and is associated with lower breast cancer mortality and reduced risk of recurrence.Both exercise-induced factors secreted into circulation(exerkines)and bioactive molecules contained in skeletal muscle secretome have been proposed to affect the tumor microenvironment and mediate some of the anti-carcinogenic effects of exercise.This study utilized exercise-conditioned human serum obtained from breast cancer patients during chemotherapy and skeletal myotubes’secretome after mechanical loading to investigate their effects on breast cancer cells in vitro.Methods Breast cancer patients participated in a 12-week exercise training program during their chemotherapy,and blood serum was collected immediately before and after an exercise session in the 2nd and 12th weeks of training.Skeletal myoblasts were differentiated into myotubes and subjected to mechanical stretching to collect their secretome(stretch medium(SM)).Hormone-sensitive Michigan Cancer Foundation-7(MCF-7)and triple-negative M.D.Anderson-Metastatic Breast-231(MDA-MB-231)breast cancer cells were treated with either human serum or with the skeletal myotubes’secretome to examine their metabolic activity,migration,cytotoxicity levels and apoptosis regulation.Results The exercise-conditioned serum obtained from breast cancer patients who were subjected to the 12-week training during chemotherapy resulted in reduced metabolic activity(p<0.001)and increased lactate dehydrogenase activity(cytotoxicity)(p<0.001)in both MCF-7 and MDA-MB-231 breast cancer cells when compared with the control condition.Moreover,incubation of breast cancer cells with the post-exercise serum induced apoptosis in MCF-7 and MDA-MB-231 cells,as indicated by increase in DNA damage and the percentage of necrotic cells(p<0.05)when compared to pre-exercise condition.Similarly,a significant decrease(p<0.001)was observed in the metabolic activity of MCF-7 cells treated with the SM,along with increased cytotoxicity(p<0.05),compared to the cells cultured with the regular growth media.Comparable though not as profound effects were observed in MDA-MB-231 cells when treated with the SM secretome.Furthermore,the expression of apoptosis-inducing Caspase-7(p<0.001)and Caspase-8(p<0.01)proteins was increased,whereas cell survival-regulating factors interleukin-8(IL-8)(p<0.001),superoxide dismutase-2(p<0.05),Fas cell surface death receptor(p<0.05),and vascular endothelial growth factor(p<0.01)were downregulated in the SM-treated MCF-7 cells.In addition,the migrating behavior of MCF-7 cells was diminished,and higher levels of DNA damage were observed in cells treated with either SM or non-stretch media.Conclusion Both exercise-conditioned serum of breast cancer patients and skeletal myotubes secretome after mechanical loading can reduce the metabolic activity,promote cell toxicity and DNA damage,modulate the protein expression of crucial cell survival-regulating factors,and lead to apoptosis in breast cancer cells.These findings suggest that even after cancer diagnosis,exercise may exert beneficial effects additive to chemotherapy against breast cancer prognosis.展开更多
Current scientific endeavours in the field of geroscience have begun to reveal how factors such as exercise could modulate the brain aging process.In this review,we ask how exercise could potentially modulate aging,an...Current scientific endeavours in the field of geroscience have begun to reveal how factors such as exercise could modulate the brain aging process.In this review,we ask how exercise could potentially modulate aging,and by extension,the development of Alzheimer’s Disease(AD).Furthermore,we discuss how exercise could mitigate the cascade of debilitating manifestations in AD.Mechanistically,we discuss how biomolecules such as brain-derived neurotrophic factor(BDNF)and its cognate receptor,tropomyosin receptor kinase B(TrkB)could change during the life course and how its signalling pathways could be altered with exercise(acute sessions or chronic training).Tackling these questions could help the scientific and medical community mitigate age-related decline in terms of neurological functions.展开更多
Purpose:Regular exercise can reduce incidence and progression of breast cancer,but the mechanisms for such effects are not fully understood.The purpose of this study was to examine the mechanisms behind the protective...Purpose:Regular exercise can reduce incidence and progression of breast cancer,but the mechanisms for such effects are not fully understood.The purpose of this study was to examine the mechanisms behind the protective effects of exercise.Methods:We used a variety of rodent and human experimental model systems to determine whether exercise training can reduce tumor burden in breast cancer and to identify mechanism associated with any exercise training effects on tumor burden.Results:We show that voluntary wheel running slows tumor development in the mammary specific polyomavirus middle T antigen overexpression(MMTV-PyMT)mouse model of breast cancer but only when mice are not housed alone.We identify the proteoglycan decorin as a contraction-induced secretory factor that systemically increases in patients with breast cancer immediately following exercise.Moreover,high expression of decorin in tumors is associated with improved prognosis in patients,while treatment of breast cancer cells in vitro with decorin reduces cell proliferation.Notwithstanding,when we overexpressed decorin in murine muscle or injected recombinant decorin systemically into mouse models of breast cancer,elevated plasma decorin concentrations did not result in higher tumor decorin levels and tumor burden was not improved.Conclusion:Exercise training is anti-tumorigenic in a mouse model of luminal breast cancer,but the effect is abrogated by social isolation.The proteoglycan decorin is an exercise-induced secretory protein,and tumor decorin levels are positively associated with improved prognosis in patients.The hypothesis that elevated plasma decorin is a mechanism by which exercise training improves breast cancer progression in humans is not,however,supported by our pre-clinical data since elevated circulating decorin did not increase tumor decorin levels in these models.展开更多
Background: Resistance exercise leads to improved muscle function and metabolic homeostasis.Yet how circadian rhythm impacts exercise outcomes and its molecular transduction remains elusive.Methods: Human volunteers w...Background: Resistance exercise leads to improved muscle function and metabolic homeostasis.Yet how circadian rhythm impacts exercise outcomes and its molecular transduction remains elusive.Methods: Human volunteers were subjected to 4 weeks of resistance training protocols at different times of day to assess training outcomes and their associations with myokine irisin.Based on rhythmicity of Fibronectin type III domain containing 5(FNDC5/irisin),we trained wild type and FNDC5 knockout mice at late active phase(high FNDC5/irisin level)or late rest phase(low FNDC5/irisin level)to analyze exercise benefits on muscle function and metabolic homeostasis.Molecular analysis was performed to understand the regulatory mechanisms of FNDC5 rhythmicity and downstream signaling transduction in skeletal muscle.Results: In this study,we showed that regular resistance exercises performed at different times of day resulted in distinct training outcomes in humans,including exercise benefits and altered plasma metabolomics.We found that muscle FNDC5/irisin levels exhibit rhythmicity.Consistent with human data,compared to late rest phase(low irisin level),mice trained chronically at late active phase(high irisin level)gained more muscle capacity along with improved metabolic fitness and metabolomics/lipidomics profiles under a high-fat diet,whereas these differences were lost in FNDC5 knockout mice.Mechanistically,Basic helix-loop-helix ARNT like 1(BMAL1)and Peroxisome proliferative activated receptor,gamma,coactivator 1 alpha 4(PGC1α4)induce FNDC5/irisin transcription and rhythmicity,and the signaling is transduced viaαV integrin in muscle.Conclusion: Together,our results offered novel insights that exercise performed at distinct times of day determines training outcomes and metabolic benefits through the rhythmic regulation of the BMAL1/PGC1α4-FNDC5/irisin axis.展开更多
Inflammatory bowel disease(IBD),comprising Crohn’s disease and ulcerative colitis,represents the two predominant clinical entities within this spectrum of gastrointestinal disorders.Current evidence indicates that th...Inflammatory bowel disease(IBD),comprising Crohn’s disease and ulcerative colitis,represents the two predominant clinical entities within this spectrum of gastrointestinal disorders.Current evidence indicates that the etiology of IBD is multifactorial,involving a complex interplay between host genetic susceptibility and environmental determinants.In recent years,non-pharmacological strategies such as physical exercise and vagus nerve stimulation have gained increasing attention as adjunctive therapeutic approaches.Vagus nerve stimulation has emerged as a promising therapeutic modality,particularly in conditions characterized by autonomic dysfunction and diminished vagal tone.Conversely,vagotomy,by disrupting vagal control,abolishes parasympathetic reflexes and may potentiate inflammatory responses and exacerbate IBD symptomatology under stress conditions.Physical exercise has likewise been investigated as a non-pharmacological intervention in Crohn’s disease and ulcerative colitis.Although the precise mechanisms remain to be fully elucidated,accumulating evidence suggests that skeletal muscle contractions promote the secretion of myokines,with recognized anti-inflammatory properties.These myokines act on the intestinal microenvironment,conferring protection against malignant transformation and modulating the composition and function of the gut microbiota.In this review,we critically examine the interplay between physical exercise,vagus nerve stimulation,and vagotomy in the pathophysiology and management of IBD,with particular emphasis on their immunomodulatory and therapeutic potential.展开更多
文摘Background:Insufficient physical activity and prolonged sedentary behavior have emerged as major global public health challenges.Short bouts(≤10 min)of accumulated exercise(SBAE)throughout the day may be a promising strategy to mitigate the adverse effects of prolonged sitting and promote physical activity,ultimately promoting overall health.However,previous ambiguity in defining this concept has resulted in a fragmented and inconsistent evidence base,impeding practical applications,the development of guidelines,and policymaking.The purpose of this study is to establish an operational definition of SBAE by synthesizing systematic reviews and research trials alongside an expert consensus.Additionally,it seeks to evaluate acute and long-term efficacy and feasibility,providing evidence-based recommendations for practice and future research directions.Methods:A literature search was performed across PubMed and Web of Science,followed by systematic screening and summarization of eligible studies based on predefined inclusion criteria.Inclusion criteria encompassed various modes/types of SBAE(bouts lasting≤10 min,performed multiple times daily with≥30 min intervals);both aerobic and resistance exercise were considered.Relevant systematic reviews and research trials were included.Methodological quality,risk of bias,and evidence certainty were assessed.Expert consensus was obtained through a survey to evaluate recommendations and agreement levels on findings.Results:After analyzing 27 systematic reviews,135 research studies,and an expert consensus involving 48 researchers from 11 countries,SBAE is defined as any exercise mode of activity,regardless of intensity,that is accumulated in either continuous or intermittent bouts lasting≤10 min per session(including multiple intermittent sets)that are performed multiple times(≥2 sessions/day)per day,with intervals of≥30 min between bouts or otherwise sufficient time for recovery.When used to interrupt prolonged periods of sedentary time,SBAE mitigates the acute adverse effects of sedentary behavior on more than 10 clinical biomarkers of endocrine,cardiovascular,and brain health/function among adults of diverse ages and conditions.Moreover,SBAE was superior for improving acute glycemic control compared to a single continuous exercise session.As a long-term intervention(average of 11 weeks),SBAE can improve over 20 health outcomes,including peak oxygen uptake,resting blood pressure,and metabolic health.Additionally,SBAE might be more effective than continuous exercise for improving longer-term glycemic control and body composition.Long-term completion rates for SBAE interventions are generally high(95%),with low dropout rates(12%)and high adherence rates even without supervision(85%),and its safety has been preliminarily validated.Conclusion:An operational definition of SBAE is provided along with its classification and acute and long-term efficacy.Practical exercise prescription recommendations and evidence-based strategies for various populations and contexts are provided.Future research should focus on generating high-quality evidence for SBAE in 5 key areas:quantification and monitoring,population-specific responses,optimization of exercise prescriptions,intervention efficacy,and practical implementation.Additionally,addressing policy,environmental,and promotional barriers is crucial for transitioning from expert consensus to public consensus,and for facilitating the application of this strategy in real-world environments.
基金supported by National Natural Science Foundation of China[NO.11932013].
文摘This study aims to explore the impact of fatigue induced by different limb exercises on cerebral cortical oxygenation levels and functional connectivity strength using functional near-infrared spectroscopy(fNIRS).Fatigue was induced using an upper limb ergometer or a lower limb ergometer,with the load increasing gradually each minute.fNIRS covering the prefrontal cortex and motor cortex were used to collect data during the resting state,both before and after fatigue induction.A two-way ANOVA was conducted to examine differences in oxyhemoglobin(HbO_(2))and functional connectivity before and after fatigue induction in both groups,with the significance level set at 0.05.Exercise-induced fatigue in both the upper and lower limbs leads to a significant decrease in cerebral cortical oxygenation levels.Upper limb fatigue leads to a significant reduction in functional connectivity,there were significant decreases in connectivity within the motor cortex,between the motor cortex and frontal regions,and between the right ventrolateral prefrontal cortex and other frontal regions.Conversely,no significant changes were observed before and after lower limb fatigue.Future studies should focus on examining the extent to which how changes in the cerebral cortex,induced by exercise fatigue,are linked to exercise-and/or performance-related outcomes.
基金supported by an AIMS fellowship grant from the University of West Florida(04523:YL)partially by the National Institutes of Health grant under Award Number R16-GM149358the National Science Foundation grant DUE 2344997.
文摘Parkinson's disease(PD)is the second most common neurodegenerative disease that affects movement and cognitive function,resulting from the loss of the neurotransmitter dopamine due to the death of dopaminergic neurons.It affects nearly one million people in the United States and 8.5 million worldwide.While there are some pharmacological and surgical options available,they only provide symptomatic relief,as there is currently no cure for PD.In contrast,exercise training,a non-pharmacological intervention,has emerged as a powerful strategy to enhance the psychological,cognitive,and physiological(motor)impairments associated with PD.Given that the beneficial effects of exercise differ based on the intensity and type of training,gaining a thorough understanding of the molecular mechanisms underlying exercise-induced protection is crucial for developing innovative therapies that improve the quality of life for PD patients around the globe.This review discusses PD pathogenesis and pathophysiology and provides recent clinical evidence of neuroprotective benefits from various exercise modalities and intensity.Furthermore,the molecular mechanisms of exercise in PD pathogenesis(e.g.,modulations on neurotrophic factors,oxidative stress,mitochondria dysfunction,endoplasmic reticulum stress,and autophagy)will be emphasized.
文摘Background: We monitored changes in salivary creatine pre-and post-high-intensity exercise in young adults while also investigating the potential correlation between salivary and serum creatine levels.Method: Saliva and serum samples were collected before and immediately after an incremental running-toexhaustion treadmill test in fifteen young adults(mean age [23.9 ± 2.9] years, eight females), with samples analyzed for guanidinoacetic acid, creatine, and creatinine using a liquid chromatography–tandem mass spectrometry method.Results: Following exercise, there was a substantial elevation in salivary creatine levels from(17.5 ± 14.2)μmol·L^(-1) to(43.6 ± 30.4) μmol·L^(-1)(p < 0.001), coupled with a significant increase in salivary creatinine from(11.3 ± 5.8) μmol·L^(-1) to(17.0 ± 9.3) μmol·L^(-1)(p = 0.04). In contrast, serum creatine levels were unaffected by exercise(p = 0.80), while creatinine levels exhibited a strong tendency to decrease post-exercise(from [81.8 ±17.5] μmol·L^(-1) to [73.1 ± 11.6] μmol·L^(-1);p = 0.06). A comparison of the slopes of the two regression lines(saliva vs. serum) revealed significant differences for both creatine(p = 0.01) and creatinine(p = 0.03).Conclusions: The above findings suggest a potential difference in the dynamics of creatine metabolites in these two bodily fluids, both pre and post-exercise.
基金supported by the National Institutes of Health for the Kansas Center for Metabolism and Obesity Research(award No.P20GM144269)support from the Center for Advancing Translational Sciences of the National Institutes of Health(award No.KL2TR002367)supported by the National Center for Advancing Translational Sciences of the National Institutes of Health(award No.TL1TR002368)。
文摘Overweight and obesity are significant public health concerns worldwide due to their association with many chronic health conditions.This has resulted in the development of various interventions focused on weight loss to reduce the associated health burden.Physical activity is an important lifestyle behavior associated with enhanced health.Evidence supports that many of the benefits of physical activity are realized independent of initial weight status or whether weight loss is achieved,with some benefits additive to what is achieved with weight loss alone.These benefits include enhanced cardiometabolic,brain,cognitive and psychological health,and others.Moreover,in adults with overweight or obesity,physical activity has independent effects on cardiorespiratory fitness,muscular strength,physical function,and mobility.There are also benefits to body composition,with physical activity improving the quality of key tissues,such as skeletal muscle,which may not occur with diet-induced weight loss.Therefore,physical activity is an important public health target for adults with overweight or obesity to provide a wide range of health benefits that extend beyond those of weight loss alone.However,physical activity recommendations and programming efforts should consider the unique characteristics of adults with overweight or obesity to be most effective,and should support a focus on mobility,physical function,and other health outcomes.
文摘Exercise produces a decrease in pain sensitivity via an effect called exercise-induced hypoalgesia(EIH).Transcranial direct current stimulation(tDCS),acting on similar analgesic mechanisms as EIH,represents a potential complementary intervention that may amplify the effects of exercise on pain.This study aimed to explore if anodal tDCS could enhance the effect of exercise on pain compared to exercise alone.A total of 35 healthy participants aged 19–37 years completed a familiarisation session followed by two separate sessions where active and sham tDCS was applied in a randomised cross-over design.The familiarisation session involved familiarisation to the pain assessment and exercise tasks,while the subsequent tDCS sessions involved pain sensitivity assessment,exercise and either anodal tDCS or sham tDCS.tDCS doses were applied at 2 mA over the primary motor cortex for 10 min,with the reference electrode placed over the contralateral supraorbital area.The exercise task involved a sustained isometric grip strength contraction at 35%of maximal voluntary contraction(MVC)until volitional exhaustion.Pain sensitivity was evaluated as pressure pain threshold before tDCS,after tDCS,and after exercise.Across both tDCS conditions,pain threshold was higher after exercise when compared to pre-and post-tDCS measurement.This increase in pain threshold did not differ between active and sham tDCS conditions.Our findings suggest that the hypoalgesic effects of active anodal tDCS over the motor cortex prior to exercise are no greater than the effects of sham tDCS prior to exercise.
基金supported by National Institutes of Health(NIH)Grants AG063944 and AG080047 to KAM.
文摘Advances in skeletal muscle omics has expanded our understanding of exercise-induced adaptations at the molecular level.Over the past 2 decades,transcriptome studies in muscle have detailed acute and chronic responses to resistance,endurance,and concurrent exercise,focusing on variables such as training status,nutrition,age,sex,and metabolic health profile.Multi-omics approaches,such as the integration of transcriptomic and epigenetic data,along with emerging ribosomal RNA sequencing advancements,have further provided insights into how skeletal muscle adapts to exercise across the lifespan.Downstream of the transcriptome,proteomic and phosphoproteomic studies have identified novel regulators of exercise adaptations,while single-cell/nucleus and spatial sequencing technologies promise to evolve our understanding of cellular specialization and communication in and around skeletal muscle cells.This narrative review highlights(a)the historical foundations of exercise omics in skeletal muscle,(b)current research at 3 layers of the omics cascade(DNA,RNA,and protein),and(c)applications of single-cell omics and spatial sequencing technologies to study skeletal muscle adaptation to exercise.Further elaboration of muscle's global molecular footprint using multi-omics methods will help researchers and practitioners develop more effective and targeted approaches to improve skeletal muscle health as well as athletic performance.
基金provided by the Joint Fund for Regional Innovation and Development(U23A20471)Beijing Natural Science Foundation(L242161,L241073,and 7232354)。
文摘The purpose is to explore the effects of Exercise rehabilitation(ER)on bone mineral density(BMD)of the knee,muscle strength(MS),and physical function(PF)after ACL rupture.Finally,A total of 58 patients were randomized into 2 groups(Control Group[CON]:conventional treatment,male=16,female=13,age=[31.63±8.01]years;Exercise rehabilitation group[ER]:6-week ER on CON basis,male=17,female=12,age=[31.26±7.07]years).At baseline and 6 weeks,the knee BMD was measured using DEXA,MS and PF measures were recorded by isokinetic strength test,IKDC,Lysholm,and VAS score.T-tests,analysis of variance(ANOVA),and Mann-Whitney tests were used for comparisons.The BMD outcomes:after a 6-week period,the BMD of the CON([1.47±0.24]g·cm^(-2))was significantly lower than that of the ER([1.65±0.37]g·cm^(-2))at lateral condyle of femur(LCF)(p=0.041).MS outcomes:at 6 weeks,the relative peak torque(RPT)of the quadriceps and hamstrings during concentric contractions in ER group were significantly higher than that in CON group(p<0.001,p=0.017).Similarly,during eccentric contractions in ER group,the RPT of the quadriceps and the H/Q ratio revealed significant variations from the CON group(p=0.033,p=0.043).PF outcomes:the IKDC,Lysholm,and VAS scores of the ER group were significantly improved compared to the CON group(p<0.001,p<0.001,p=0.002).The conclusion is that 6 weeks of ER intervention for patients with ACL rupture can effectively delay the decline of BMD in the LCF of the knee joint,and enhance the restoration of MS and PF.This provides guidance for clinical rehabilitation.
基金supported by STI2030-Major Projects,No.2022ZD0207600(to LZ)the National Natural Science Foundation of China,Nos.32070955(to LZ),U22A20301(to KFS)+3 种基金the Natural Science Foundation of Guangdong Province,No.2021A1515012197(to HO)Guangzhou Core Medical Disciplines Project,No.2021-2023(to HO)Key Research and Development Plan of Ningxia Hui Automomous Region,No.2022BEG01004(to KFS)Science and Technology Program of Guangzhou,China,No.202007030012(to KFS and LZ)。
文摘Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.
文摘We read with great interest the recent article by Valenzuela et al.1titled“Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability:Insights from McArdle disease”published in the Journal of Sport and Health Science The study's exploration of the effects of varying carbohydrate(CHO)doses on exercise capacity in Mc Ardle disease,a condition characterized by complete muscle glycogen unavailability,is a significant contribution to the field of sports science and metabolic disorders.
基金supported by funding provided to BJG from the Natural Sciences and Engineering Research Council of Canada(NSERCgrant no.402635).
文摘Objectives:Aerobic exercise training can increase skeletal muscle mitochondrial content.Supine exercise training with legs above the heart potentially augments these increases.However,the impact of supine exercise training on mitochondrial biogenesis and cardiovascular adaptations remains unclear.Methods:In this single-centred,randomized,parallel arm trial,19 recreationally active individuals underwent seven sessions of either supine with legs up(SUP;n=9,6 females)or upright with legs down(UP;n=10,7 females)aerobic training on a recumbent bike at 71±7%and 71±2%of peak work rate(WRpeak),respectively.The study aimed to test the effects of training with decreased muscle oxygenation on indices of muscle mitochondrial remodelling.Secondary outcomes included exercise performance,muscle oxygenation,and cardiovascular responses.Results:Secondary outcomes revealed significant interaction effects for time to fatigue(TTF)and WRpeak in the SUP group during supine testing,suggesting enhanced exercise tolerance and performance.No between group interaction effects were observed for upright testing.No clear effects on mitochondrial biogenesis were observed based on expression of mitochondrial protein subunits and transcriptional regulators.Acutely,HRpeak was lower during the SUP Test compared to the UP Test.No central cardiovascular adaptations were observed following training.Conclusions:Our exploratory analyses showed that supine aerobic training more effectively improves supine exercise tolerance and performance compared with upright training,despite no differences in measured proteins related to mitochondrial biogenesis.Further research is needed to elucidate the mechanisms underlying these postural-specific training effects.Registration:clinicaltrials.gov:NCT04151095.
基金financial support from the general electric (GE) healthcareAustralian Research Council Discovery Project (DP200101476)+5 种基金in parts by National Institutes of Health (NIH) grants (R01 AR077604, R01 EB002524, R01 AR079431, P41 EB02706)Stanford Graduate FellowshipThe University of Queensland Graduate ScholarshipNational Health and Medical Research Council of Australia Fellowship (#1194937)Wu Tsai Human Performance Alliance at Stanford Universitythe Joe and Clara Tsai Foundation
文摘Background While Nordic hamstring exercise(NHE)training has been shown to reduce hamstring strains,the muscle-specific adaptations to NHE across the 4 hamstrings remain unclear.This study investigates architectural and microstructural adaptations of the biceps femoris short head(BFsh),biceps femoris long head(BFlh),semitendinosus(ST),and semimembranosus(SM)in response to an NHE intervention.Methods Eleven subjects completed 9 weeks of supervised NHE training followed by 3 weeks of detraining.Magnetic resonance imaging was performed at pre-training,post-training,and detraining to assess architectural(volume,fiber tract length,and fiber tract angle)and microstructural(axial(AD),mean(MD),radial(RD)diffusivities,and fractional anisotropy(FA))parameters of the 4 hamstrings.Results NHE training induced significant but non-uniform hamstring muscle hypertrophy(BFsh:22%,BFlh:9%,ST:26%,SM:6%)and fiber tract length increase(BFsh:11%,BFlh:7%,ST:18%,SM:10%).AD(5%),MD(4%),and RD(5%)showed significant increases,but fiber tract angle and FA remained unchanged.After detraining,only ST showed a significant reduction(8%)in volume,which remained higher than the pre-training value.While fiber tract lengths returned to baseline,AD,MD,and RD remained higher than pre-training levels for all hamstrings.Conclusion The 9-week NHE training substantially increased hamstring muscle volume with greater hypertrophy in ST and BFsh.Hypertrophy was accompanied by increases in fiber tract lengths and cross-sections(increased RD).After 3 weeks of detraining,fiber tract length gains across all hamstrings declined,emphasizing the importance of sustained training to maintain all the protective adaptations.
基金supported by the National Natural Science Foundation of China(32471186 and 31771318)the 14th Five-Year-Plan Advantageous and Characteristic Disciplines(Groups)of Colleges and Universities in Hubei Province for Exercise and Brain Science+1 种基金as well as the Leading Talent Program and Innovative Start-up Foundation from Wuhan Sports University to Ning Chensupported by the Hubei Natural Science Foundation(2022CFB929)and China Postdoctoral Science Foundation(2023M732727)to Tong Wu.
文摘It is well known that appropriate aerobic exercise can effectively alleviate fatty liver and enhance brain function.The concept of multi-organ crosstalk coordinating disease progression has become the current research hot topic.However,there remains an urgent need to elucidate its specific mechanisms.This study aimed to explore the impact of a high-fat diet(HFD)on liver health and cognitive function,and to further uncover the regulatory effect of aerobic exercise by liver-specific activating transcription factor 3(Atf3)knockout(ATF3cKO)mice in a“liver-brain”axis mode.The 5-week-old C57BL/6 and ATF3cKO mice were fed with HFD for 32 weeks,and sequentially subjected to aerobic exercise intervention at the 20th week for another 12 consecutive weeks.Meanwhile,C57BL/6 mice were provided with a normal diet as the control group.The functional parameters of liver and brain of all mice were assessed.Cognitive capacity of all mice was assessed by the Morris water maze(MWM).Inflammatory factors in the serum and brain of mice were quantified using enzyme-linked immunosorbent assay(ELISA),and the expression of inflammasomes was detected by immunohistochemistry(IHC).Additionally,the activation of nuclear factor-κB(NF-κB)and phosphoinositide 3-kinase(PI3K)signal pathways was analyzed by Western blotting.In this study,HFD impaired hepatic and brain functions,while aerobic exercise and liver-specific Atf3 knockout suppressed inflammatory factors in the peripheral circulation through hepatoprotective mechanisms,thereby attenuating cerebral inflammation and preserving neurological integrity,as well as mitigating HFD-induced cognitive decline.
基金supported by the National Natural Science Foundation of China(32471186 and 32071176)the 14th Five-Year-Plan Advantageous and Characteristic Disciplines(Groups)of Colleges and Universities in Hubei Province for Exercise and Brain Science from Hubei Provincial Department of Educationthe Leading Talent Program and Innovative Start-Up Foundation from Wuhan Sports University.
文摘Nutrigenomics is an emerging research field to investigate the interactions between food components and genes and elucidate their impacts on health and diseases.Exercise,another critical factor influencing human health,is intricately linked with nutrition and genetics,and is influenced by a combination of genetic background,lifestyle choice,and environmental factors.The high-throughput sequencing technologies and advanced bioinformatic tools have offered researchers to delve deeper into how individual genetic expression responses to exercise and how dietary interventions can enhance exercise performance and recovery through the gene expression changes and modifications.Among these mechanisms,gene expression emerges as the primary focus,highlighting its role in linking nutrients and exercise to metabolic pathways,muscle synthesis,and inflammation.While epigenetic modifications are briefly considered,the emphasis remains on how direct and indirect influences on gene expression drive physiological adaptations.Herein,the article reviews recent advancements in nutrigenomics within the context of exercise science,exploring gene-regulating mechanisms affected by specific nutrients and dietary patterns on exercise capacity,muscle synthesis,and damage repair.It also outlines the potential applications of personalized nutrition plans in athletic training and general fitness.In addition,this article addresses current challenges and potential issues in the practical implementation of nutrigenomics in exercise-induced health promotion.Future studies should emphasize interdisciplinary collaboration to unravel the intricate gene-nutrition-exercise interaction networks,thereby providing a solid theoretical foundation and technological support for the advancement of precision exercise nutrition.
基金supported by the National Natural Science Foundation of China(82571021,32070751 and 31871435)the Shanghai Natural Science Foundation(25ZR1401328)the Program for Overseas High-level talents at Shanghai Institutions of Higher Learning(TP2022100)。
文摘L-Theanine(LTA)is a non-protein amino acid mainly found in tea plants with many beneficial effects.Exercise exerts a wide range of benefits in metabolic health.Here,we show that exercise or gastric lavage intervention on mice with LTA improves diet-induced nonalcoholic steatohepatitis(NASH)in mice.Meanwhile,combinatory therapy shows that exercise and LTA synergistically improve obesity-related metabolic disorders and NASH phenotypes,including hepatic steatosis,inflammation,cell death and oxidative stress.In vivo studies indicate that LTA inhibits free fatty acid(FFA)-induced hepatocyte injury,including steatosis,oxidative stress and apoptosis.Knockdown of Nrf2 blunts the role of LTA in inhibiting FFA-induced hepatocyte oxidative stress and dysfunction.Mechanistically,LTA increases theα-ketoglutarate(α-KG)level in hepatocytes,which increases the transcription of Nrf2 by inducing active DNA demethylation on its promoter.Moreover,LTA promote the aboveα-KG/Nrf2 axis in synergy with exercise,thereby more efficiently inhibiting hepatic oxidative stress and ameliorating diet-induced NASH in mice.Our results suggest that,through promoting theα-KG/Nrf2 axis-mediated anti-oxidative pathway,the combination of LTA and exercise may provide an effective measure for the prevention and control of NASH.
基金the Biochemical Imaging Center at UmeåUniversity and the National Microscopy Infrastructure(VR-RFI 2019-00217),for providing assistance in microscopy.
文摘Background Regular exercise training provides significant health benefits among cancer survivors and is associated with lower breast cancer mortality and reduced risk of recurrence.Both exercise-induced factors secreted into circulation(exerkines)and bioactive molecules contained in skeletal muscle secretome have been proposed to affect the tumor microenvironment and mediate some of the anti-carcinogenic effects of exercise.This study utilized exercise-conditioned human serum obtained from breast cancer patients during chemotherapy and skeletal myotubes’secretome after mechanical loading to investigate their effects on breast cancer cells in vitro.Methods Breast cancer patients participated in a 12-week exercise training program during their chemotherapy,and blood serum was collected immediately before and after an exercise session in the 2nd and 12th weeks of training.Skeletal myoblasts were differentiated into myotubes and subjected to mechanical stretching to collect their secretome(stretch medium(SM)).Hormone-sensitive Michigan Cancer Foundation-7(MCF-7)and triple-negative M.D.Anderson-Metastatic Breast-231(MDA-MB-231)breast cancer cells were treated with either human serum or with the skeletal myotubes’secretome to examine their metabolic activity,migration,cytotoxicity levels and apoptosis regulation.Results The exercise-conditioned serum obtained from breast cancer patients who were subjected to the 12-week training during chemotherapy resulted in reduced metabolic activity(p<0.001)and increased lactate dehydrogenase activity(cytotoxicity)(p<0.001)in both MCF-7 and MDA-MB-231 breast cancer cells when compared with the control condition.Moreover,incubation of breast cancer cells with the post-exercise serum induced apoptosis in MCF-7 and MDA-MB-231 cells,as indicated by increase in DNA damage and the percentage of necrotic cells(p<0.05)when compared to pre-exercise condition.Similarly,a significant decrease(p<0.001)was observed in the metabolic activity of MCF-7 cells treated with the SM,along with increased cytotoxicity(p<0.05),compared to the cells cultured with the regular growth media.Comparable though not as profound effects were observed in MDA-MB-231 cells when treated with the SM secretome.Furthermore,the expression of apoptosis-inducing Caspase-7(p<0.001)and Caspase-8(p<0.01)proteins was increased,whereas cell survival-regulating factors interleukin-8(IL-8)(p<0.001),superoxide dismutase-2(p<0.05),Fas cell surface death receptor(p<0.05),and vascular endothelial growth factor(p<0.01)were downregulated in the SM-treated MCF-7 cells.In addition,the migrating behavior of MCF-7 cells was diminished,and higher levels of DNA damage were observed in cells treated with either SM or non-stretch media.Conclusion Both exercise-conditioned serum of breast cancer patients and skeletal myotubes secretome after mechanical loading can reduce the metabolic activity,promote cell toxicity and DNA damage,modulate the protein expression of crucial cell survival-regulating factors,and lead to apoptosis in breast cancer cells.These findings suggest that even after cancer diagnosis,exercise may exert beneficial effects additive to chemotherapy against breast cancer prognosis.
文摘Current scientific endeavours in the field of geroscience have begun to reveal how factors such as exercise could modulate the brain aging process.In this review,we ask how exercise could potentially modulate aging,and by extension,the development of Alzheimer’s Disease(AD).Furthermore,we discuss how exercise could mitigate the cascade of debilitating manifestations in AD.Mechanistically,we discuss how biomolecules such as brain-derived neurotrophic factor(BDNF)and its cognate receptor,tropomyosin receptor kinase B(TrkB)could change during the life course and how its signalling pathways could be altered with exercise(acute sessions or chronic training).Tackling these questions could help the scientific and medical community mitigate age-related decline in terms of neurological functions.
基金supported by an NHMRC Investigator Grant (APP1194141)supported by project grants from the NHMRC (APP1042465, APP1041760, and APP1156511)。
文摘Purpose:Regular exercise can reduce incidence and progression of breast cancer,but the mechanisms for such effects are not fully understood.The purpose of this study was to examine the mechanisms behind the protective effects of exercise.Methods:We used a variety of rodent and human experimental model systems to determine whether exercise training can reduce tumor burden in breast cancer and to identify mechanism associated with any exercise training effects on tumor burden.Results:We show that voluntary wheel running slows tumor development in the mammary specific polyomavirus middle T antigen overexpression(MMTV-PyMT)mouse model of breast cancer but only when mice are not housed alone.We identify the proteoglycan decorin as a contraction-induced secretory factor that systemically increases in patients with breast cancer immediately following exercise.Moreover,high expression of decorin in tumors is associated with improved prognosis in patients,while treatment of breast cancer cells in vitro with decorin reduces cell proliferation.Notwithstanding,when we overexpressed decorin in murine muscle or injected recombinant decorin systemically into mouse models of breast cancer,elevated plasma decorin concentrations did not result in higher tumor decorin levels and tumor burden was not improved.Conclusion:Exercise training is anti-tumorigenic in a mouse model of luminal breast cancer,but the effect is abrogated by social isolation.The proteoglycan decorin is an exercise-induced secretory protein,and tumor decorin levels are positively associated with improved prognosis in patients.The hypothesis that elevated plasma decorin is a mechanism by which exercise training improves breast cancer progression in humans is not,however,supported by our pre-clinical data since elevated circulating decorin did not increase tumor decorin levels in these models.
基金supported by funds from National Key Research and Development Program of China (2019YFA0904500 to LX, 2023YFA1800400 to LX, and 2018YFE0113500 to JX)the National Natural Science Foundation of China (82301777 to MG, 32222024 to LX, 32325024 to XM, 32071148 to LX, and 91957116 to CX)+6 种基金Fundamental Research Funds for the Central Universities, Science and Technology Commission of Shanghai Municipality (21140904300 to XM and 22ZR1421200 to LX)Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-09-E00042 to JX)Key Project of 2022 Higher Education Scientific Research Planning Project of China Association of Higher Education (22TY0218 to FS)Youth Fund for Humanities and Social Sciences Research of the Ministry of Education (22YJC890023 to FS)Postdoctoral Fellowship Program of CPSF (GZB20230219 to MG)China Postdoctoral Science Foundation (2023M741183 to MG)ECNU public platform for Innovation (011).
文摘Background: Resistance exercise leads to improved muscle function and metabolic homeostasis.Yet how circadian rhythm impacts exercise outcomes and its molecular transduction remains elusive.Methods: Human volunteers were subjected to 4 weeks of resistance training protocols at different times of day to assess training outcomes and their associations with myokine irisin.Based on rhythmicity of Fibronectin type III domain containing 5(FNDC5/irisin),we trained wild type and FNDC5 knockout mice at late active phase(high FNDC5/irisin level)or late rest phase(low FNDC5/irisin level)to analyze exercise benefits on muscle function and metabolic homeostasis.Molecular analysis was performed to understand the regulatory mechanisms of FNDC5 rhythmicity and downstream signaling transduction in skeletal muscle.Results: In this study,we showed that regular resistance exercises performed at different times of day resulted in distinct training outcomes in humans,including exercise benefits and altered plasma metabolomics.We found that muscle FNDC5/irisin levels exhibit rhythmicity.Consistent with human data,compared to late rest phase(low irisin level),mice trained chronically at late active phase(high irisin level)gained more muscle capacity along with improved metabolic fitness and metabolomics/lipidomics profiles under a high-fat diet,whereas these differences were lost in FNDC5 knockout mice.Mechanistically,Basic helix-loop-helix ARNT like 1(BMAL1)and Peroxisome proliferative activated receptor,gamma,coactivator 1 alpha 4(PGC1α4)induce FNDC5/irisin transcription and rhythmicity,and the signaling is transduced viaαV integrin in muscle.Conclusion: Together,our results offered novel insights that exercise performed at distinct times of day determines training outcomes and metabolic benefits through the rhythmic regulation of the BMAL1/PGC1α4-FNDC5/irisin axis.
文摘Inflammatory bowel disease(IBD),comprising Crohn’s disease and ulcerative colitis,represents the two predominant clinical entities within this spectrum of gastrointestinal disorders.Current evidence indicates that the etiology of IBD is multifactorial,involving a complex interplay between host genetic susceptibility and environmental determinants.In recent years,non-pharmacological strategies such as physical exercise and vagus nerve stimulation have gained increasing attention as adjunctive therapeutic approaches.Vagus nerve stimulation has emerged as a promising therapeutic modality,particularly in conditions characterized by autonomic dysfunction and diminished vagal tone.Conversely,vagotomy,by disrupting vagal control,abolishes parasympathetic reflexes and may potentiate inflammatory responses and exacerbate IBD symptomatology under stress conditions.Physical exercise has likewise been investigated as a non-pharmacological intervention in Crohn’s disease and ulcerative colitis.Although the precise mechanisms remain to be fully elucidated,accumulating evidence suggests that skeletal muscle contractions promote the secretion of myokines,with recognized anti-inflammatory properties.These myokines act on the intestinal microenvironment,conferring protection against malignant transformation and modulating the composition and function of the gut microbiota.In this review,we critically examine the interplay between physical exercise,vagus nerve stimulation,and vagotomy in the pathophysiology and management of IBD,with particular emphasis on their immunomodulatory and therapeutic potential.
