Introduction: Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the global population and poses a remarkably serious threat to human health.
Objectives: The effect and potential molecular mechanisms of combined cold exposure and exercise intervention on NAFLD remain unclear.
Materials and methods: A high-fat diet-induced NAFLD mouse model was used. Twenty-four NAFLD mice were divided into three groups and subjected to cold exposure (5°C), regular-temperature exercise (22°C), or combined cold exposure and exercise (5°C) for 8 wk, 5 d·wk -1 , once daily for 1 h each session. Intervention effects were evaluated through bodyweight, liver mass, liver/bodyweight ratio, blood lipid profile, circulating fibroblast growth factor 21 (FGF21) levels, and liver histopathology. Immunoblotting and quantitative PCR were used to assess the protein and gene expression of liver FGF21, β-klotho, and FGFR1 to preliminarily elucidate the molecular mechanisms underlying NAFLD improvement by combined cold exposure and exercise.
Results: Compared with cold exposure or regular-temperature exercise alone, combined cold exposure and exercise significantly reduced the bodyweight, liver weight, and liver/bodyweight ratio in the NAFLD mice. The levels of blood lipids, circulating FGF21, and liver glycogen also significantly decreased. Furthermore, the combined intervention significantly reduced liver fat deposition and fibrosis and significantly increased the expression of FGFR1 and β-klotho proteins, suggesting the activation of the FGF21-β-klotho/FGFR1 signaling pathway.
Conclusions: This preclinical study demonstrates that combined cold exposure and exercise synergistically alleviates NAFLD progression in animal models, primarily by activating the FGF21-β-klotho/FGFR1 pathway to enhance lipid metabolism and reduce liver injury. These findings highlight the translational potential of dual environmental and behavioral interventions, providing a mechanistic foundation for developing nonpharmacological therapies targeting metabolic pathways in humans, particularly for NAFLD patients resistant to conventional lifestyle modifications or pharmacotherapy.
{"title":"Combined Cold Exposure and Exercise Improves NAFLD: Mechanistic Insights.","authors":"Xue Geng, Zhijian Rao, Jianhong Zhang, Peng Huang, Chaoyi Qu, Dongzhe Wu, Qiangman Wei, Shijie Liu, Xiaokan Zhuang, Jiexiu Zhao","doi":"10.1249/MSS.0000000000003719","DOIUrl":"10.1249/MSS.0000000000003719","url":null,"abstract":"<p><strong>Introduction: </strong>Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the global population and poses a remarkably serious threat to human health.</p><p><strong>Objectives: </strong>The effect and potential molecular mechanisms of combined cold exposure and exercise intervention on NAFLD remain unclear.</p><p><strong>Materials and methods: </strong>A high-fat diet-induced NAFLD mouse model was used. Twenty-four NAFLD mice were divided into three groups and subjected to cold exposure (5°C), regular-temperature exercise (22°C), or combined cold exposure and exercise (5°C) for 8 wk, 5 d·wk -1 , once daily for 1 h each session. Intervention effects were evaluated through bodyweight, liver mass, liver/bodyweight ratio, blood lipid profile, circulating fibroblast growth factor 21 (FGF21) levels, and liver histopathology. Immunoblotting and quantitative PCR were used to assess the protein and gene expression of liver FGF21, β-klotho, and FGFR1 to preliminarily elucidate the molecular mechanisms underlying NAFLD improvement by combined cold exposure and exercise.</p><p><strong>Results: </strong>Compared with cold exposure or regular-temperature exercise alone, combined cold exposure and exercise significantly reduced the bodyweight, liver weight, and liver/bodyweight ratio in the NAFLD mice. The levels of blood lipids, circulating FGF21, and liver glycogen also significantly decreased. Furthermore, the combined intervention significantly reduced liver fat deposition and fibrosis and significantly increased the expression of FGFR1 and β-klotho proteins, suggesting the activation of the FGF21-β-klotho/FGFR1 signaling pathway.</p><p><strong>Conclusions: </strong>This preclinical study demonstrates that combined cold exposure and exercise synergistically alleviates NAFLD progression in animal models, primarily by activating the FGF21-β-klotho/FGFR1 pathway to enhance lipid metabolism and reduce liver injury. These findings highlight the translational potential of dual environmental and behavioral interventions, providing a mechanistic foundation for developing nonpharmacological therapies targeting metabolic pathways in humans, particularly for NAFLD patients resistant to conventional lifestyle modifications or pharmacotherapy.</p>","PeriodicalId":18426,"journal":{"name":"Medicine and Science in Sports and Exercise","volume":" ","pages":"1988-2000"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-04-04DOI: 10.1249/MSS.0000000000003724
Alexander D Paish, Neil D Eves, Chris J McNeil
Purpose: Most studies applying repeated neuromuscular electrical stimulation (NMES) to assess intrinsic contractile properties employ frequencies considerably greater than the mean motor unit discharge rate (MUDR) for a given force level. It is hypothesized that force loss increases with stimulation frequency, but this has not been evaluated in the same pool of participants when other parameters are unchanged. Furthermore, there is a paucity of research investigating possible sex-based differences for force loss during an NMES protocol, with the presence or absence of a group difference seemingly dependent on stimulation frequency. To address these limitations, we compared force loss of electrically evoked contractions at (10 Hz), slightly above (15 Hz), and well above (30 Hz) the expected mean MUDR of the quadriceps at 25% maximal voluntary force.
Methods: On three separate occasions, 24 participants (12 females) received 3 min of intermittent NMES (10, 15, or 30 Hz) over the quadriceps of the dominant leg.
Results: Force impairment increased with NMES frequency (19.8 ± 14.5, 42.6 ± 8.1, and 52.9 ± 4.7 for 10, 15, and 30 Hz, respectively), with no significant differences between sexes. Relative to the start of each task, the rates of force development (RFD) and relaxation (RFR) slowed markedly during the 10-, 15-, and 30-Hz fatiguing protocols (RFD: 42.1 ± 13.5, 61.6 ± 13.2, and 75.9 ± 9.8; RFR: 38.0 ± 13.9, 64.2 ± 9.1, and 80.4 ± 5.0, respectively). RFD impairment was less at 10 compared with 15 and 30 Hz, whereas the slowing of RFR increased with NMES frequency. Post-hoc analysis revealed no sex-based differences at any time point for RFD or RFR.
Conclusions: These findings underscore the impact of stimulus frequency on muscle fatigability and highlight a lack of sex-based differences for electrically evoked force loss, emphasizing the need for appropriate frequency selection in NMES protocols.
{"title":"Frequency Matters: The Influence of Stimulation Frequency on Force Loss for Human Females and Males.","authors":"Alexander D Paish, Neil D Eves, Chris J McNeil","doi":"10.1249/MSS.0000000000003724","DOIUrl":"10.1249/MSS.0000000000003724","url":null,"abstract":"<p><strong>Purpose: </strong>Most studies applying repeated neuromuscular electrical stimulation (NMES) to assess intrinsic contractile properties employ frequencies considerably greater than the mean motor unit discharge rate (MUDR) for a given force level. It is hypothesized that force loss increases with stimulation frequency, but this has not been evaluated in the same pool of participants when other parameters are unchanged. Furthermore, there is a paucity of research investigating possible sex-based differences for force loss during an NMES protocol, with the presence or absence of a group difference seemingly dependent on stimulation frequency. To address these limitations, we compared force loss of electrically evoked contractions at (10 Hz), slightly above (15 Hz), and well above (30 Hz) the expected mean MUDR of the quadriceps at 25% maximal voluntary force.</p><p><strong>Methods: </strong>On three separate occasions, 24 participants (12 females) received 3 min of intermittent NMES (10, 15, or 30 Hz) over the quadriceps of the dominant leg.</p><p><strong>Results: </strong>Force impairment increased with NMES frequency (19.8 ± 14.5, 42.6 ± 8.1, and 52.9 ± 4.7 for 10, 15, and 30 Hz, respectively), with no significant differences between sexes. Relative to the start of each task, the rates of force development (RFD) and relaxation (RFR) slowed markedly during the 10-, 15-, and 30-Hz fatiguing protocols (RFD: 42.1 ± 13.5, 61.6 ± 13.2, and 75.9 ± 9.8; RFR: 38.0 ± 13.9, 64.2 ± 9.1, and 80.4 ± 5.0, respectively). RFD impairment was less at 10 compared with 15 and 30 Hz, whereas the slowing of RFR increased with NMES frequency. Post-hoc analysis revealed no sex-based differences at any time point for RFD or RFR.</p><p><strong>Conclusions: </strong>These findings underscore the impact of stimulus frequency on muscle fatigability and highlight a lack of sex-based differences for electrically evoked force loss, emphasizing the need for appropriate frequency selection in NMES protocols.</p>","PeriodicalId":18426,"journal":{"name":"Medicine and Science in Sports and Exercise","volume":" ","pages":"2009-2020"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-04-04DOI: 10.1249/MSS.0000000000003721
Rahul Ghosal, James W White, Olivia Finnegan, Srihari Nelakuditi, Trey Brown, Russ Pate, Greg Welk, Massimiliano DE Zambotti, Yuan Wang, Sarah Burkart, Elizabeth L Adams, Bridget Armstrong, Michael W Beets, R Glenn Weaver
Introduction: This study examined the potential of a device agnostic approach for predicting physical activity energy expenditure (PAEE) from research-grade and consumer wearable accelerometry and heart rate (HR) raw data compared with indirect calorimetry in children.
Methods: Two hundred thirty-one 5- to 12-yr-olds (52.4% male) of diverse skin tone and body weights participated in a 60-min protocol with multiple activities at varying intensities. Children wore two of three consumer wearables (Apple Watch Series 7, Garmin Vivoactive 4S, Fitbit Sense) and a research-grade accelerometer (ActiGraph GT9X) on their nondominant wrist, and a chest-placed, research-grade HR monitor (Actiheart 5, ECG), concurrently. Children also wore a K5 criterion measure of PAEE (i.e., COSMED K5). Cross-sectional time series (CSTS), generalized additive mixed effects model (GAMM), and random forest (RF) were used to estimate minute-by-minute PAEE from features extracted from raw accelerometry and HR data. Variance explained ( R2 ), in addition to other metrics, evaluated agreement between estimated and criterion measurements.
Results: For the research-grade devices (i.e., ActiGraph accelerometry and Actiheart HR), R2 values were 0.74, 0.74, and 0.76 for CSTS, GAMM, and RF, respectively. For Apple, R2 values were 0.77, 0.76, and 0.78; Garmin's values were 0.73, 0.73, and 0.75; and Fitbit's values were 0.63, 0.65, and 0.67 for CSTS, GAMM, and RF, respectively. Across all other evaluation metrics, a similar pattern was observed with Fitbit performing the worst but with little variability between the modeling approaches or the other devices.
Conclusions: Except for Fitbit, accelerometry and HR data from consumer wearables predicted PAEE comparably to research-grade devices, and there was little variability across modeling approach. These outcomes support deploying a consumer wearable device-agnostic approach for PAEE estimation in children.
{"title":"Leveraging Accelerometry and Heart Rate Data from Consumer Wearables to Predict Physical Activity in Children: A Device Agnostic Approach.","authors":"Rahul Ghosal, James W White, Olivia Finnegan, Srihari Nelakuditi, Trey Brown, Russ Pate, Greg Welk, Massimiliano DE Zambotti, Yuan Wang, Sarah Burkart, Elizabeth L Adams, Bridget Armstrong, Michael W Beets, R Glenn Weaver","doi":"10.1249/MSS.0000000000003721","DOIUrl":"10.1249/MSS.0000000000003721","url":null,"abstract":"<p><strong>Introduction: </strong>This study examined the potential of a device agnostic approach for predicting physical activity energy expenditure (PAEE) from research-grade and consumer wearable accelerometry and heart rate (HR) raw data compared with indirect calorimetry in children.</p><p><strong>Methods: </strong>Two hundred thirty-one 5- to 12-yr-olds (52.4% male) of diverse skin tone and body weights participated in a 60-min protocol with multiple activities at varying intensities. Children wore two of three consumer wearables (Apple Watch Series 7, Garmin Vivoactive 4S, Fitbit Sense) and a research-grade accelerometer (ActiGraph GT9X) on their nondominant wrist, and a chest-placed, research-grade HR monitor (Actiheart 5, ECG), concurrently. Children also wore a K5 criterion measure of PAEE (i.e., COSMED K5). Cross-sectional time series (CSTS), generalized additive mixed effects model (GAMM), and random forest (RF) were used to estimate minute-by-minute PAEE from features extracted from raw accelerometry and HR data. Variance explained ( R2 ), in addition to other metrics, evaluated agreement between estimated and criterion measurements.</p><p><strong>Results: </strong>For the research-grade devices (i.e., ActiGraph accelerometry and Actiheart HR), R2 values were 0.74, 0.74, and 0.76 for CSTS, GAMM, and RF, respectively. For Apple, R2 values were 0.77, 0.76, and 0.78; Garmin's values were 0.73, 0.73, and 0.75; and Fitbit's values were 0.63, 0.65, and 0.67 for CSTS, GAMM, and RF, respectively. Across all other evaluation metrics, a similar pattern was observed with Fitbit performing the worst but with little variability between the modeling approaches or the other devices.</p><p><strong>Conclusions: </strong>Except for Fitbit, accelerometry and HR data from consumer wearables predicted PAEE comparably to research-grade devices, and there was little variability across modeling approach. These outcomes support deploying a consumer wearable device-agnostic approach for PAEE estimation in children.</p>","PeriodicalId":18426,"journal":{"name":"Medicine and Science in Sports and Exercise","volume":" ","pages":"2083-2092"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12766645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2024-10-08DOI: 10.1249/MSS.0000000000003251
David M Shaw, Fabrice Merien, Andrea Braakhuis, E Maunder, Deborah K Dulson
{"title":"Effect of a Ketogenic Diet on Submaximal Exercise Capacity and Efficiency in Runners-Erratum.","authors":"David M Shaw, Fabrice Merien, Andrea Braakhuis, E Maunder, Deborah K Dulson","doi":"10.1249/MSS.0000000000003251","DOIUrl":"10.1249/MSS.0000000000003251","url":null,"abstract":"","PeriodicalId":18426,"journal":{"name":"Medicine and Science in Sports and Exercise","volume":" ","pages":"2098"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-04-04DOI: 10.1249/MSS.0000000000003725
Andrew T Askow, Takeshi M Barnes, Zan Zupancic, Max T Deutz, Kevin J M Paulussen, Colleen F McKenna, Amadeo F Salvador, Alexander V Ulanov, Scott A Paluska, Jared W Willard, Steven J Petruzzello, Nicholas A Burd
Background: Protein ingestion stimulates muscle protein synthesis (MPS) rates to support the turnover of skeletal muscle protein mass. However, dietary patterns consist of a variety of protein foods with different amino acid compositions consumed at multiple meal times throughout the day. Omnivorous (OMN) and vegan (VGN) dietary patterns may differentially stimulate MPS. Moreover, the distribution and frequency of protein intake may also play an important anabolic regulatory role.
Objective: We aimed to determine the effect of OMN and VGN dietary patterns and protein distribution (balanced (B) and unbalanced (UB)) in regulating changes in daily myofibrillar protein synthesis rates during a 9-d resistance training intervention.
Design: Forty healthy, physically active males and females (28 males, 12 females; 25 ± 4 yr; body mass index, 24.1 ± 2.1 kg·m -2 ) consumed a weight-maintenance diet providing 1.1-1.2 g·kg -1 ·d -1 of dietary protein from an OMN or VGN dietary pattern with UB (10%, 30%, and 60% of daily protein at meals 1, 2, and 3, respectively) or B (20% of daily protein at five eating occasions) distribution. Participants completed whole-body resistance exercise three times during the controlled feeding trial while consuming deuterated water (D 2 O) for the measurement of daily myofibrillar protein synthesis rates.
Results: The percent kilocalories from carbohydrate was higher ( P = 0.045) in the OMN compared with VGN groups, but no other differences in dietary intakes were observed. Myofibrillar protein synthesis rates did not differ between the OMN-UB (3.04% ± 1.85%·d -1 ), OMN-B (2.43% ± 1.21%·d -1 ), VGN-UB (2.52% ± 1.77%·d -1 ), and VGN-B (2.49% ± 1.56%·d -1 ) groups (all P > 0.05).
Conclusions: Our results demonstrated that the anabolic action of animal versus vegan dietary patterns is similar. Moreover, there is no regulatory influence of distribution between the two dietary patterns on the stimulation of myofibrillar protein synthesis rates in young adults.This trial was registered with ClinicalTrials.gov (NCT04232254).
{"title":"Impact of Vegan Diets on Resistance Exercise-Mediated Myofibrillar Protein Synthesis in Healthy Young Males and Females: A Randomized Controlled Trial.","authors":"Andrew T Askow, Takeshi M Barnes, Zan Zupancic, Max T Deutz, Kevin J M Paulussen, Colleen F McKenna, Amadeo F Salvador, Alexander V Ulanov, Scott A Paluska, Jared W Willard, Steven J Petruzzello, Nicholas A Burd","doi":"10.1249/MSS.0000000000003725","DOIUrl":"10.1249/MSS.0000000000003725","url":null,"abstract":"<p><strong>Background: </strong>Protein ingestion stimulates muscle protein synthesis (MPS) rates to support the turnover of skeletal muscle protein mass. However, dietary patterns consist of a variety of protein foods with different amino acid compositions consumed at multiple meal times throughout the day. Omnivorous (OMN) and vegan (VGN) dietary patterns may differentially stimulate MPS. Moreover, the distribution and frequency of protein intake may also play an important anabolic regulatory role.</p><p><strong>Objective: </strong>We aimed to determine the effect of OMN and VGN dietary patterns and protein distribution (balanced (B) and unbalanced (UB)) in regulating changes in daily myofibrillar protein synthesis rates during a 9-d resistance training intervention.</p><p><strong>Design: </strong>Forty healthy, physically active males and females (28 males, 12 females; 25 ± 4 yr; body mass index, 24.1 ± 2.1 kg·m -2 ) consumed a weight-maintenance diet providing 1.1-1.2 g·kg -1 ·d -1 of dietary protein from an OMN or VGN dietary pattern with UB (10%, 30%, and 60% of daily protein at meals 1, 2, and 3, respectively) or B (20% of daily protein at five eating occasions) distribution. Participants completed whole-body resistance exercise three times during the controlled feeding trial while consuming deuterated water (D 2 O) for the measurement of daily myofibrillar protein synthesis rates.</p><p><strong>Results: </strong>The percent kilocalories from carbohydrate was higher ( P = 0.045) in the OMN compared with VGN groups, but no other differences in dietary intakes were observed. Myofibrillar protein synthesis rates did not differ between the OMN-UB (3.04% ± 1.85%·d -1 ), OMN-B (2.43% ± 1.21%·d -1 ), VGN-UB (2.52% ± 1.77%·d -1 ), and VGN-B (2.49% ± 1.56%·d -1 ) groups (all P > 0.05).</p><p><strong>Conclusions: </strong>Our results demonstrated that the anabolic action of animal versus vegan dietary patterns is similar. Moreover, there is no regulatory influence of distribution between the two dietary patterns on the stimulation of myofibrillar protein synthesis rates in young adults.This trial was registered with ClinicalTrials.gov (NCT04232254).</p>","PeriodicalId":18426,"journal":{"name":"Medicine and Science in Sports and Exercise","volume":" ","pages":"1923-1934"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-04-04DOI: 10.1249/MSS.0000000000003722
Pin-Shi Ni, Meng-Meng Jia, Jia-Han He, Zhi Yu, Fang-Hui Li
Objective: This study aimed to investigate the molecular mechanisms underlying the improvement of aged skeletal muscle atrophy by high-intensity interval training (HIIT) combined with glycine supplementation.
Methods: Male C57BL/6J mice aged 19 months ( n = 16) were randomly assigned to old sedentary (OSED), HIIT, OSED + glycine, and HIIT + glycine (H-Gly) groups for an 8-wk intervention. Maximum grip strength and running speed were assessed. Myocyte apoptosis was detected by TUNEL staining; myofiber cross-sectional area was measured by laminin staining; reactive oxygen species in myocytes were detected by dihydroethidium staining. Western blot and RT-qPCR were used to measure protein and gene expression levels related to senescence, apoptosis, and ferroptosis in myocytes. Chemical methods were employed to detect changes in malondialdehyde, lipid peroxide, glutathione, glutathione-oxidized, and total glutathione contents. RNA-seq technology was utilized to screen for key differentially expressed genes. AutoDockTools software was used for molecular docking predictions between glycine and key differential proteins.
Results: H-Gly group mice showed an improved maximum grip strength and muscle fiber cross-sectional area, with a significant reduction in TUNEL-positive cells. RNA-seq analysis revealed a high correlation between ferroptosis pathway genes and Slc25a25 ion transport-related genes, which was further validated by the detection of ferroptosis-related markers. Molecular docking indicated that glycine has binding sites with Slc25a25, with the highest binding energy of -3.7 kcal·mol -1 .
Conclusions: Glycine supplementation has a significant synergistic effect with HIIT in increasing muscle mass and grip strength in aged muscle. The mechanism might be associated with the decrease of Slc25a25-mediated ferroptosis.
{"title":"High-Intensity Interval Training Combined with Glycine Supplementation Drives Ferroptosis Resistance to Counteract Skeletal Muscle Atrophy in Aging Mice.","authors":"Pin-Shi Ni, Meng-Meng Jia, Jia-Han He, Zhi Yu, Fang-Hui Li","doi":"10.1249/MSS.0000000000003722","DOIUrl":"10.1249/MSS.0000000000003722","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the molecular mechanisms underlying the improvement of aged skeletal muscle atrophy by high-intensity interval training (HIIT) combined with glycine supplementation.</p><p><strong>Methods: </strong>Male C57BL/6J mice aged 19 months ( n = 16) were randomly assigned to old sedentary (OSED), HIIT, OSED + glycine, and HIIT + glycine (H-Gly) groups for an 8-wk intervention. Maximum grip strength and running speed were assessed. Myocyte apoptosis was detected by TUNEL staining; myofiber cross-sectional area was measured by laminin staining; reactive oxygen species in myocytes were detected by dihydroethidium staining. Western blot and RT-qPCR were used to measure protein and gene expression levels related to senescence, apoptosis, and ferroptosis in myocytes. Chemical methods were employed to detect changes in malondialdehyde, lipid peroxide, glutathione, glutathione-oxidized, and total glutathione contents. RNA-seq technology was utilized to screen for key differentially expressed genes. AutoDockTools software was used for molecular docking predictions between glycine and key differential proteins.</p><p><strong>Results: </strong>H-Gly group mice showed an improved maximum grip strength and muscle fiber cross-sectional area, with a significant reduction in TUNEL-positive cells. RNA-seq analysis revealed a high correlation between ferroptosis pathway genes and Slc25a25 ion transport-related genes, which was further validated by the detection of ferroptosis-related markers. Molecular docking indicated that glycine has binding sites with Slc25a25, with the highest binding energy of -3.7 kcal·mol -1 .</p><p><strong>Conclusions: </strong>Glycine supplementation has a significant synergistic effect with HIIT in increasing muscle mass and grip strength in aged muscle. The mechanism might be associated with the decrease of Slc25a25-mediated ferroptosis.</p>","PeriodicalId":18426,"journal":{"name":"Medicine and Science in Sports and Exercise","volume":" ","pages":"1852-1865"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-05-05DOI: 10.1249/MSS.0000000000003711
Jan Plesek, Joseph Hamill, Michal Burda, Steriani Elavsky, Jiri Skypala, Jan Urbaczka, Julia Freedman-Silvernail, David Zahradnik, Jaroslav Uchyti, Daniel Jandacka
{"title":"Running Distance and Biomechanical Risk Factors for Plantar Fasciitis: A 1-yr Prospective 4HAIE Cohort Study - Corrigendum.","authors":"Jan Plesek, Joseph Hamill, Michal Burda, Steriani Elavsky, Jiri Skypala, Jan Urbaczka, Julia Freedman-Silvernail, David Zahradnik, Jaroslav Uchyti, Daniel Jandacka","doi":"10.1249/MSS.0000000000003711","DOIUrl":"10.1249/MSS.0000000000003711","url":null,"abstract":"","PeriodicalId":18426,"journal":{"name":"Medicine and Science in Sports and Exercise","volume":" ","pages":"2100"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-28DOI: 10.1249/MSS.0000000000003839
Derek P D Bornath, Seth F McCarthy, Jessica A L Tucker, Tamara R Cohen, Philip J Medeiros, Tom J Hazell
Introduction: Exercise interventions are less effective in generating weight loss in females compared to males suggesting that the menstrual cycle may be important. Fluctuations in ovarian hormones are proposed to alter the appetite-regulatory response to exercise across the menstrual cycle and no study has assessed the response in all distinct hormonal phases.
Purpose: To compare post-exercise appetite-regulating parameters following a single bout of MICT across three distinct menstrual phases.
Methods: Thirteen females (24 ± 4 y; 24.8 ± 5.4 kg·m-2) completed 30 min of moderate-intensity continuous training (MICT) running in the follicular phase (FP), ovulatory phase (OP), and luteal phase (LP). Acylated ghrelin, active glucagon-like peptide-1 (GLP-1), plasma glucose, insulin, blood lactate, and appetite perceptions were measured pre-exercise, 0 min, 30 min, 60 min, and 120 min post-exercise. Energy intake was recorded for a 3-day period (day before, of, and after each session).
Results: Acylated ghrelin was not different across phases (p = 0.672, ηp2 = 0.032) and only showed a main effect of time (p = 0.006, ηp2 = 0.757) increasing with time. Active GLP-1 was not different across phases (p = 0.735, ηp2 = 0.025) and had a main effect of time (p < 0.001, ηp2 = 0.569) decreasing with time. Appetite perceptions were not different across phases (p = 0.577, ηp2 = 0.045) and exhibited a main effect of time (p < 0.001, ηp2 = 0.786) increasing with time. There was no effect of phase for energy intake (p = 0.544, ηp2 = 0.065). Finally, there were no differences in plasma glucose, insulin, or blood lactate across phases (p > 0.421, ηp2 < 0.070).
Conclusions: There were no divergent appetite responses following MICT running across three hormonally distinct phases (mid-FP, OP, mid-LP) of the menstrual cycle in young eumenorrheic females not using oral contraceptives.
{"title":"No Effect of Menstrual Phase on Appetite-Regulatory Parameters Following a Moderate-Intensity Exercise Session.","authors":"Derek P D Bornath, Seth F McCarthy, Jessica A L Tucker, Tamara R Cohen, Philip J Medeiros, Tom J Hazell","doi":"10.1249/MSS.0000000000003839","DOIUrl":"https://doi.org/10.1249/MSS.0000000000003839","url":null,"abstract":"<p><strong>Introduction: </strong>Exercise interventions are less effective in generating weight loss in females compared to males suggesting that the menstrual cycle may be important. Fluctuations in ovarian hormones are proposed to alter the appetite-regulatory response to exercise across the menstrual cycle and no study has assessed the response in all distinct hormonal phases.</p><p><strong>Purpose: </strong>To compare post-exercise appetite-regulating parameters following a single bout of MICT across three distinct menstrual phases.</p><p><strong>Methods: </strong>Thirteen females (24 ± 4 y; 24.8 ± 5.4 kg·m-2) completed 30 min of moderate-intensity continuous training (MICT) running in the follicular phase (FP), ovulatory phase (OP), and luteal phase (LP). Acylated ghrelin, active glucagon-like peptide-1 (GLP-1), plasma glucose, insulin, blood lactate, and appetite perceptions were measured pre-exercise, 0 min, 30 min, 60 min, and 120 min post-exercise. Energy intake was recorded for a 3-day period (day before, of, and after each session).</p><p><strong>Results: </strong>Acylated ghrelin was not different across phases (p = 0.672, ηp2 = 0.032) and only showed a main effect of time (p = 0.006, ηp2 = 0.757) increasing with time. Active GLP-1 was not different across phases (p = 0.735, ηp2 = 0.025) and had a main effect of time (p < 0.001, ηp2 = 0.569) decreasing with time. Appetite perceptions were not different across phases (p = 0.577, ηp2 = 0.045) and exhibited a main effect of time (p < 0.001, ηp2 = 0.786) increasing with time. There was no effect of phase for energy intake (p = 0.544, ηp2 = 0.065). Finally, there were no differences in plasma glucose, insulin, or blood lactate across phases (p > 0.421, ηp2 < 0.070).</p><p><strong>Conclusions: </strong>There were no divergent appetite responses following MICT running across three hormonally distinct phases (mid-FP, OP, mid-LP) of the menstrual cycle in young eumenorrheic females not using oral contraceptives.</p>","PeriodicalId":18426,"journal":{"name":"Medicine and Science in Sports and Exercise","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-25DOI: 10.1249/MSS.0000000000003836
Alejandro Santos-Lozano, Abel Plaza-Florido, Pedro Carrera-Bastos, Inmaculada Pérez-Prieto, Alejandro Hernández-Belmonte, Fatemeh Kamalinejad, Beatriz G Gálvez, Juan A López, Jorge Lumbreras, Cecilia Rincón-Castanedo, Asunción Martín-Ruiz, Steven J Fleck, Alejandro López-Soto, Natalia Yanguas-Casás, Tomàs Pinós, Alejandro Lucia, Carmen Fiuza-Luces
Purpose: Cardiorespiratory fitness (CRF) and muscle strength are associated with cancer risk/mortality in adults. However, there is yet no evidence for pediatric tumors. This study investigated the association of CRF and muscle strength with several tumor-related phenotypes in an aggressive childhood malignancy, high-risk neuroblastoma (HR-NB).
Methods: Twelve mice bearing orthotopic HR-NB were studied. CRF and muscle strength were assessed using treadmill and grip strength testing, respectively. The following tumor-related outcomes were studied: survival, clinical severity, tumor weight/volume, metastasis, and intratumor immune infiltrates. Additionally, tumor samples underwent quantitative proteomic analysis via liquid chromatography-tandem mass spectrometry. Spearman correlations (or logistic regression) were performed between CRF/muscle strength and the abovementioned variables. Proteins significantly correlated with CRF or muscle strength were mapped into protein-protein interaction (PPI) networks using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database.
Results: CRF was inversely correlated with clinical severity score (r = -0.657, p = 0.020). Of 6,840 identified tumor proteins, 76 correlated significantly with CRF (19 positively, 57 negatively), whereas 194 correlated with muscle strength (97 positively, 97 negatively). Proteins correlated with CRF were primarily involved in metabolic and structural pathways, including angiotensinogen and elastin. In turn, muscle strength-associated proteins were more abundant, and included keratin family proteins (e.g., keratin, type I cytoskeletal 14 and type II cytoskeletal 5), proteins involved in cell adhesion (e.g., desmoglein-1-alpha), and translational regulators (e.g., eukaryotic initiation factor 4A). Network analysis revealed significant enrichment in structural organization and cellular adhesion pathways.
Conclusions: Besides the association of CRF with clinical severity of the tumor, distinct novel tumor proteomic signatures associated with CRF and muscle strength were identified, highlighting potential mechanisms linking physical fitness with childhood cancer biology.
目的:心肺功能(CRF)和肌肉力量与成人癌症风险/死亡率相关。然而,目前还没有证据表明儿童肿瘤。本研究调查了侵袭性儿童恶性高风险神经母细胞瘤(HR-NB)中CRF和肌肉力量与几种肿瘤相关表型的关系。方法:对12只原位HR-NB小鼠进行实验研究。CRF和肌肉力量分别通过跑步机和握力测试进行评估。研究了以下肿瘤相关结果:生存、临床严重程度、肿瘤重量/体积、转移和肿瘤内免疫浸润。此外,通过液相色谱-串联质谱法对肿瘤样本进行定量蛋白质组学分析。在CRF/肌力与上述变量之间进行Spearman相关性(或逻辑回归)。使用Search Tool for Retrieval of Interacting Genes/Proteins (STRING)数据库,将与CRF或肌肉力量显著相关的蛋白质映射到蛋白质-蛋白质相互作用(PPI)网络中。结果:CRF与临床严重程度评分呈负相关(r = -0.657, p = 0.020)。在鉴定的6840种肿瘤蛋白中,76种与CRF显著相关(19种正相关,57种负相关),而194种与肌肉力量相关(97种正相关,97种负相关)。与CRF相关的蛋白主要参与代谢和结构途径,包括血管紧张素原和弹性蛋白。反过来,肌肉力量相关蛋白更丰富,包括角蛋白家族蛋白(如角蛋白,I型细胞骨架14和II型细胞骨架5),参与细胞粘附的蛋白(如粘粒蛋白-1- α)和翻译调节因子(如真核起始因子4A)。网络分析显示结构组织和细胞粘附途径显著富集。结论:除了CRF与肿瘤的临床严重程度相关外,还发现了与CRF和肌肉力量相关的独特的新肿瘤蛋白质组学特征,突出了将身体健康与儿童癌症生物学联系起来的潜在机制。
{"title":"Tumor Signatures of Physical Fitness: Insights from a Preclinical Model.","authors":"Alejandro Santos-Lozano, Abel Plaza-Florido, Pedro Carrera-Bastos, Inmaculada Pérez-Prieto, Alejandro Hernández-Belmonte, Fatemeh Kamalinejad, Beatriz G Gálvez, Juan A López, Jorge Lumbreras, Cecilia Rincón-Castanedo, Asunción Martín-Ruiz, Steven J Fleck, Alejandro López-Soto, Natalia Yanguas-Casás, Tomàs Pinós, Alejandro Lucia, Carmen Fiuza-Luces","doi":"10.1249/MSS.0000000000003836","DOIUrl":"https://doi.org/10.1249/MSS.0000000000003836","url":null,"abstract":"<p><strong>Purpose: </strong>Cardiorespiratory fitness (CRF) and muscle strength are associated with cancer risk/mortality in adults. However, there is yet no evidence for pediatric tumors. This study investigated the association of CRF and muscle strength with several tumor-related phenotypes in an aggressive childhood malignancy, high-risk neuroblastoma (HR-NB).</p><p><strong>Methods: </strong>Twelve mice bearing orthotopic HR-NB were studied. CRF and muscle strength were assessed using treadmill and grip strength testing, respectively. The following tumor-related outcomes were studied: survival, clinical severity, tumor weight/volume, metastasis, and intratumor immune infiltrates. Additionally, tumor samples underwent quantitative proteomic analysis via liquid chromatography-tandem mass spectrometry. Spearman correlations (or logistic regression) were performed between CRF/muscle strength and the abovementioned variables. Proteins significantly correlated with CRF or muscle strength were mapped into protein-protein interaction (PPI) networks using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database.</p><p><strong>Results: </strong>CRF was inversely correlated with clinical severity score (r = -0.657, p = 0.020). Of 6,840 identified tumor proteins, 76 correlated significantly with CRF (19 positively, 57 negatively), whereas 194 correlated with muscle strength (97 positively, 97 negatively). Proteins correlated with CRF were primarily involved in metabolic and structural pathways, including angiotensinogen and elastin. In turn, muscle strength-associated proteins were more abundant, and included keratin family proteins (e.g., keratin, type I cytoskeletal 14 and type II cytoskeletal 5), proteins involved in cell adhesion (e.g., desmoglein-1-alpha), and translational regulators (e.g., eukaryotic initiation factor 4A). Network analysis revealed significant enrichment in structural organization and cellular adhesion pathways.</p><p><strong>Conclusions: </strong>Besides the association of CRF with clinical severity of the tumor, distinct novel tumor proteomic signatures associated with CRF and muscle strength were identified, highlighting potential mechanisms linking physical fitness with childhood cancer biology.</p>","PeriodicalId":18426,"journal":{"name":"Medicine and Science in Sports and Exercise","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-04-03DOI: 10.1249/MSS.0000000000003717
Marion Crouzier, Stéphane Baudry, Benedicte Vanwanseele
Purpose: Previous work showed altered mechanical properties of the Achilles tendon in the presence of tendinopathy, considering the Achilles tendon as a homogeneous structure with the gastrocnemius medialis (GM) subtendon representative of it. However, the Achilles tendon consists of three semi-independent structures: the GM, gastrocnemius lateralis (GL), and soleus (SOL) subtendons, each independently pulled by their respective muscle. The aim of this study was (i) to compare the mechanical properties of the different Achilles subtendons in humans in vivo by considering the force of each muscle within the triceps surae group and (ii) to determine whether the loss of stiffness in the presence of tendinopathy is specific to individual subtendons. We hypothesized that (i) stiffness would differ between subtendons in healthy participants and that (ii) the loss of stiffness in people with Achilles tendinopathy compared with healthy controls would not affect the three subtendons identically.
Methods: Fourteen participants with tendinopathy and 14 controls performed ramped isometric plantarflexions. Simultaneously, the elongation of the three subtendons was recorded, and an estimate of the force pulling on each was made (from muscle activation and volume). Stiffness was calculated from the individual muscle index of force-subtendon elongation relationships.
Results: Results showed that regardless of the group, SOL stiffness was significantly higher than stiffness of both gastrocnemii (muscle effect: P < 0.001). A muscle-group interaction showed specific loss of stiffness of GL in Achilles tendinopathy compared with controls ( P = 0.029, d = 1.3), with no between-group difference for GM or SOL (both P > 0.925, d = 0.3).
Conclusions: This study supports the hypothesis that the biomechanical properties of the Achilles tendon differ between subtendons and further shows that the loss of stiffness in Achilles tendinopathy is specific to the GL subtendon.
{"title":"Achilles Subtendons Stiffness Differ in People with and without Achilles Tendinopathy.","authors":"Marion Crouzier, Stéphane Baudry, Benedicte Vanwanseele","doi":"10.1249/MSS.0000000000003717","DOIUrl":"10.1249/MSS.0000000000003717","url":null,"abstract":"<p><strong>Purpose: </strong>Previous work showed altered mechanical properties of the Achilles tendon in the presence of tendinopathy, considering the Achilles tendon as a homogeneous structure with the gastrocnemius medialis (GM) subtendon representative of it. However, the Achilles tendon consists of three semi-independent structures: the GM, gastrocnemius lateralis (GL), and soleus (SOL) subtendons, each independently pulled by their respective muscle. The aim of this study was (i) to compare the mechanical properties of the different Achilles subtendons in humans in vivo by considering the force of each muscle within the triceps surae group and (ii) to determine whether the loss of stiffness in the presence of tendinopathy is specific to individual subtendons. We hypothesized that (i) stiffness would differ between subtendons in healthy participants and that (ii) the loss of stiffness in people with Achilles tendinopathy compared with healthy controls would not affect the three subtendons identically.</p><p><strong>Methods: </strong>Fourteen participants with tendinopathy and 14 controls performed ramped isometric plantarflexions. Simultaneously, the elongation of the three subtendons was recorded, and an estimate of the force pulling on each was made (from muscle activation and volume). Stiffness was calculated from the individual muscle index of force-subtendon elongation relationships.</p><p><strong>Results: </strong>Results showed that regardless of the group, SOL stiffness was significantly higher than stiffness of both gastrocnemii (muscle effect: P < 0.001). A muscle-group interaction showed specific loss of stiffness of GL in Achilles tendinopathy compared with controls ( P = 0.029, d = 1.3), with no between-group difference for GM or SOL (both P > 0.925, d = 0.3).</p><p><strong>Conclusions: </strong>This study supports the hypothesis that the biomechanical properties of the Achilles tendon differ between subtendons and further shows that the loss of stiffness in Achilles tendinopathy is specific to the GL subtendon.</p>","PeriodicalId":18426,"journal":{"name":"Medicine and Science in Sports and Exercise","volume":" ","pages":"1636-1645"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}