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Rashid FA, Anwar W, Kandakurti PK, Al Qawasmeh KHA, Latif MF, Tirmazy SH, Omara M, Hazari A. Physical rehabilitation program for cardiorespiratory health and quality of life among breast cancer survivors in UAE: a randomized control trial. BMC Cancer 2025; 25:705. [PMID: 40241061 PMCID: PMC12001381 DOI: 10.1186/s12885-025-14005-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 03/24/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND Breast cancer treatment has improved significantly, contributing to a 5-year relative survival rate of 99% for localized cases. However, post-treatment survivors are reported to have significantly poor cardiovascular fitness which affects their health-related quality of life (HRQoL). In the United Arab Emirates (UAE), evidence for practice addressing post-treatment concerns is scarce. OBJECTIVE To analyse the changes in cardiorespiratory fitness and HRQoL domains for breast cancer survivors in the UAE using a 2-month physical rehabilitation program. METHODOLOGY DESIGN: Parallel-group, randomized controlled trial PARTICIPANTS AND SETTING: The study included breast cancer survivors who were treated with chemotherapy and/or radiotherapy, aged 18-65 years, and able to provide informed consent. Participants were recruited by referral from Al Tawam Hospital, a national referral center for oncology, and Dubai Hospital. INTERVENTIONS The intervention group (IG) received a 2-month supervised physical rehabilitation program focusing on aerobic training with 2 supervised sessions and 3 at-home sessions per week. The sessions were held at Thumbay Physical Therapy and Rehabilitation Hospital. The control group (CG) received standard care at their treatment facility. Randomization for subject allocation was double-blinded (conducted by a third party not involved in the research). OUTCOME The changes in cardiorespiratory fitness were assessed by measuring peak oxygen uptake (VO2peak) during a 2 km walk test using Cosmed fitmate Pro and Peak Expiratory Flow Rate (PEFR) was assessed using a peak flow meter. The HRQoL was measured by the QLQ-C30 questionnaire. Outcomes were measured at baseline, post-intervention, and 3 months post-intervention. Allocation of intervention was not blinded due to the nature of the intervention; however, the outcome accessors were blinded. RESULTS A total of 62 breast cancer survivors were randomly allocated to the intervention group (n = 31) and the control group (n = 31). Data from all participants who completed the 5-month trial was analyzed. The intervention group showed a significant improvement from baseline to follow-up in terms of cardiorespiratory fitness: VO2peak increased by 8.3 ± 4.6 ml/kg/min and PEFR by 81 ± 2.73 L/min, while the control group demonstrated a decrease of 1.1 ± 2.1 ml/kg/min and 4 ± 2.48 L/min, respectively (between-group difference, p < 0.001 for both measures). The intervention program was also significantly effective in improving HRQoL in all functional domains except cognitive and social, and there was a notable reduction in the symptoms of fatigue, dyspnea, pain, and sleep disturbances (p < 0.05). CONCLUSIONS The intervention group showed significant improvement in cardiorespiratory fitness and multiple domains of HRQoL among breast cancer survivors in the UAE, which were sustained at 3 months. CLINICAL TRIALS REGISTRATION NUMBER Clinical Trials.gov NCT06013527. Registered on 28 August 2023.
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Affiliation(s)
- Fatima Abdul Rashid
- College of Health Sciences, Gulf Medical University, Ajman, United Arab Emirates
| | - Wajiha Anwar
- College of Health Sciences, Gulf Medical University, Ajman, United Arab Emirates
| | | | | | | | | | - Mohamed Omara
- Dubai Hospital, Dubai Health, Dubai, United Arab Emirates
| | - Animesh Hazari
- College of Health Sciences, Gulf Medical University, Ajman, United Arab Emirates.
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Wadan AHS, Shaaban AH, El-Sadek MZ, Mostafa SA, Moshref AS, El-Hussein A, Ellakwa DES, Mehanny SS. Mitochondrial-based therapies for neurodegenerative diseases: a review of the current literature. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04014-0. [PMID: 40163151 DOI: 10.1007/s00210-025-04014-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Accepted: 03/04/2025] [Indexed: 04/02/2025]
Abstract
Neurodegenerative disorders present significant challenges to modern medicine because of their complex etiology, pathogenesis, and progressive nature, which complicate practical treatment approaches. Mitochondrial dysfunction is an important contributor to the pathophysiology of various neurodegenerative illnesses, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). This review paper examines the current literature highlighting the multifaceted functions of mitochondria, including energy production, calcium signaling, apoptosis regulation, mitochondrial biogenesis, mitochondrial dynamics, axonal transport, endoplasmic reticulum-mitochondrial interactions, mitophagy, mitochondrial proteostasis, and their crucial involvement in neuronal health. The literature emphasizes the increasing recognition of mitochondrial dysfunction as a critical factor in the progression of neurodegenerative disorders, marking a shift from traditional symptom management to innovative mitochondrial-based therapies. By discussing mitochondrial mechanisms, including mitochondrial quality control (MQC) processes and the impact of oxidative stress, this review highlights the need for novel therapeutic strategies to restore mitochondrial function, protect neuronal connections and integrity, and slow disease progression. This comprehensive review aims to provide insights into potential interventions that could transform the treatment landscape for neurodegenerative diseases, addressing symptoms and underlying pathophysiological changes.
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Affiliation(s)
- Al-Hassan Soliman Wadan
- Department of Oral Biology, Faculty of Dentistry, Galala University, Galala Plateau, Attaka, Suez Governorate, 15888, Egypt.
| | - Ahmed H Shaaban
- Department of Biology, Faculty of Science, Galala University, Galala Plateau, Attaka,, Suez Governorate, 15888, Egypt
| | - Mohamed Z El-Sadek
- Department of Biology, Faculty of Science, Galala University, Galala Plateau, Attaka,, Suez Governorate, 15888, Egypt
| | | | - Ahmed Sherief Moshref
- Faculty of Dentistry, Galala University, Galala Plateau, Attaka, Suez Governorate, 15888, Egypt
| | - Ahmed El-Hussein
- Department of Biology, Faculty of Science, Galala University, Galala Plateau, Attaka,, Suez Governorate, 15888, Egypt
- Department of Laser Applications in Meteorology, Photochemistry, and Biotechnology, The National Institute of Laser Enhanced Science, Cairo University, Cairo, 11316, Egypt
| | - Doha El-Sayed Ellakwa
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy for Girls, Al-Azhar University, Cairo, Egypt
- Department of Biochemistry, Faculty of Pharmacy, Sinai University, Kantra Branch, Ismailia, Egypt
| | - Samah S Mehanny
- Department of Oral Biology, Faculty of Dentistry, Galala University, Galala Plateau, Attaka, Suez Governorate, 15888, Egypt
- Department of Oral Biology, Faculty of Dentistry, Cairo University, Cairo, Egypt
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Adamo KB, Goudreau AD, Corson AE, MacDonald ML, O'Rourke N, Tzaneva V. Physically active pregnancies: Insights from the placenta. Physiol Rep 2024; 12:e16104. [PMID: 38872466 PMCID: PMC11176744 DOI: 10.14814/phy2.16104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 05/03/2024] [Accepted: 05/20/2024] [Indexed: 06/15/2024] Open
Abstract
Physical activity (PA) positively influences pregnancy, a critical period for health promotion, and affects placental structure and function in ways previously overlooked. Here, we summarize the current body of literature examining the association between PA, placenta biology, and physiology while also highlighting areas where gaps in knowledge exist. PA during pregnancy induces metabolic changes, influencing nutrient availability and transporter expression in the placenta. Hormones and cytokines secreted during PA contribute to health benefits, with intricate interactions in pro- and anti-inflammatory markers. Extracellular vesicles and placental "-omics" data suggest that gestational PA can shape placental biology, affecting gene expression, DNA methylation, metabolite profiles, and protein regulation. However, whether cytokines that respond to PA alter placental proteomic profiles during pregnancy remains to be elucidated. The limited research on placenta mitochondria of physically active gestational parents (gesP), has shown improvements in mitochondrial DNA and antioxidant capacity, but the relationship between PA, placental mitochondrial dynamics, and lipid metabolism remains unexplored. Additionally, PA influences the placenta-immune microenvironment, angiogenesis, and may confer positive effects on neurodevelopment and mental health through placental changes, vascularization, and modulation of brain-derived neurotrophic factor. Ongoing exploration is crucial for unraveling the multifaceted impact of PA on the intricate placental environment.
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Affiliation(s)
- Kristi B Adamo
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Alexandra D Goudreau
- Department of Experimental Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec, Canada
| | - Abbey E Corson
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada
| | - Meaghan L MacDonald
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada
| | - Nicholas O'Rourke
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada
| | - Velislava Tzaneva
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada
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Reisman EG, Caruana NJ, Bishop DJ. Exercise training and changes in skeletal muscle mitochondrial proteins: from blots to "omics". Crit Rev Biochem Mol Biol 2024; 59:221-243. [PMID: 39288086 DOI: 10.1080/10409238.2024.2383408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 07/16/2024] [Accepted: 07/18/2024] [Indexed: 09/19/2024]
Abstract
Mitochondria are essential, membrane-enclosed organelles that consist of ∼1100 different proteins, which allow for many diverse functions critical to maintaining metabolism. Highly metabolic tissues, such as skeletal muscle, have a high mitochondrial content that increases with exercise training. The classic western blot technique has revealed training-induced increases in the relatively small number of individual mitochondrial proteins studied (∼5% of the >1100 proteins in MitoCarta), with some of these changes dependent on the training stimulus. Proteomic approaches have identified hundreds of additional mitochondrial proteins that respond to exercise training. There is, however, surprisingly little crossover in the mitochondrial proteins identified in the published human training studies. This suggests that to better understand the link between training-induced changes in mitochondrial proteins and metabolism, future studies need to move beyond maximizing protein detection to adopting methods that will increase the reliability of the changes in protein abundance observed.
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Affiliation(s)
- Elizabeth G Reisman
- Institute for Health and Sport (IHES), Victoria University, Melbourne, Australia
- Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia
| | - Nikeisha J Caruana
- Institute for Health and Sport (IHES), Victoria University, Melbourne, Australia
- Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Australia
| | - David J Bishop
- Institute for Health and Sport (IHES), Victoria University, Melbourne, Australia
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Collins BEG, Hartmann TE, Marino FE, Skein M. The Effect of a 12 Week Mixed-Modality Training Intervention on the Cardio-Metabolic Health of Rotational Shift Workers. JOURNAL OF SCIENCE IN SPORT AND EXERCISE 2024; 6:120-130. [DOI: 10.1007/s42978-022-00207-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Accepted: 10/11/2022] [Indexed: 01/05/2025]
Abstract
Abstract
Purpose
To assess the effect of a 12 week resistance or aerobic training intervention on markers of cardio-metabolic function and sleep among male rotational shift workers.
Method
Thirty-eight sedentary, apparently healthy, male rotational shift workers were recruited and randomly allocated to a non-exercise control (CON) group, 3 sessions/week of moderate intensity continuous (MICT), or resistance training (RT) for 12 weeks in a semi-supervised setting. Pre- and post-testing assessed markers of cardio-metabolic function including peak oxygen uptake (VO2peak), glucose metabolism, insulin sensitivity, body composition, inflammatory markers, and 14 day actigraphy sleep assessment.
Results
Mean session attendance across the intervention was 25 (± 7) of a possible 36 sessions. A significant group by time interaction was observed for MICT, with lower c-reactive protein (CRP) values observed post-training (P = 0.049). A significant effect for time was observed for both MICT (n = 9; P = 0.04) and RT (n = 10; P = 0.021), increasing total sleep time (TST) following a night shift post-intervention. Data redistribution regarding exercise adherence: < 24 (N-ADHERE) or ≥ 24 (ADHERE) resulted in significant pre-to-post reduction in body fat (P = 0.024) and fat mass percentage (P = 0.014) among ADHERE. No differences were observed for any intervention group on insulin sensitivity, glucose metabolism or oxygen uptake.
Conclusion
The results of the current study support exercise as a valid intervention to improve the cardio-metabolic health of rotational shift workers. Average sessional attendance suggests shift workers face barriers to exercise that may need to be addressed to improve health outcomes.
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Reisman EG, Hawley JA, Hoffman NJ. Exercise-Regulated Mitochondrial and Nuclear Signalling Networks in Skeletal Muscle. Sports Med 2024; 54:1097-1119. [PMID: 38528308 PMCID: PMC11127882 DOI: 10.1007/s40279-024-02007-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/18/2024] [Indexed: 03/27/2024]
Abstract
Exercise perturbs energy homeostasis in skeletal muscle and engages integrated cellular signalling networks to help meet the contraction-induced increases in skeletal muscle energy and oxygen demand. Investigating exercise-associated perturbations in skeletal muscle signalling networks has uncovered novel mechanisms by which exercise stimulates skeletal muscle mitochondrial biogenesis and promotes whole-body health and fitness. While acute exercise regulates a complex network of protein post-translational modifications (e.g. phosphorylation) in skeletal muscle, previous investigations of exercise signalling in human and rodent skeletal muscle have primarily focused on a select group of exercise-regulated protein kinases [i.e. 5' adenosine monophosphate-activated protein kinase (AMPK), protein kinase A (PKA), Ca2+/calmodulin-dependent protein kinase (CaMK) and mitogen-activated protein kinase (MAPK)] and only a small subset of their respective protein substrates. Recently, global mass spectrometry-based phosphoproteomic approaches have helped unravel the extensive complexity and interconnection of exercise signalling pathways and kinases beyond this select group and phosphorylation and/or translocation of exercise-regulated mitochondrial and nuclear protein substrates. This review provides an overview of recent advances in our understanding of the molecular events associated with acute endurance exercise-regulated signalling pathways and kinases in skeletal muscle with a focus on phosphorylation. We critically appraise recent evidence highlighting the involvement of mitochondrial and nuclear protein phosphorylation and/or translocation in skeletal muscle adaptive responses to an acute bout of endurance exercise that ultimately stimulate mitochondrial biogenesis and contribute to exercise's wider health and fitness benefits.
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Affiliation(s)
- Elizabeth G Reisman
- Exercise and Nutrition Research Program, Mary MacKillop Institute for Health Research, Australian Catholic University, Level 5, 215 Spring Street, Melbourne, VIC, 3000, Australia
| | - John A Hawley
- Exercise and Nutrition Research Program, Mary MacKillop Institute for Health Research, Australian Catholic University, Level 5, 215 Spring Street, Melbourne, VIC, 3000, Australia
| | - Nolan J Hoffman
- Exercise and Nutrition Research Program, Mary MacKillop Institute for Health Research, Australian Catholic University, Level 5, 215 Spring Street, Melbourne, VIC, 3000, Australia.
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Hesketh SJ. Advancing cancer cachexia diagnosis with -omics technology and exercise as molecular medicine. SPORTS MEDICINE AND HEALTH SCIENCE 2024; 6:1-15. [PMID: 38463663 PMCID: PMC10918365 DOI: 10.1016/j.smhs.2024.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 01/15/2024] [Accepted: 01/20/2024] [Indexed: 03/12/2024] Open
Abstract
Muscle atrophy exacerbates disease outcomes and increases mortality, whereas the preservation of skeletal muscle mass and function play pivotal roles in ensuring long-term health and overall quality-of-life. Muscle atrophy represents a significant clinical challenge, involving the continued loss of muscle mass and strength, which frequently accompany the development of numerous types of cancer. Cancer cachexia is a highly prevalent multifactorial syndrome, and although cachexia is one of the main causes of cancer-related deaths, there are still no approved management strategies for the disease. The etiology of this condition is based on the upregulation of systemic inflammation factors and catabolic stimuli, resulting in the inhibition of protein synthesis and enhancement of protein degradation. Numerous necessary cellular processes are disrupted by cachectic pathology, which mediate intracellular signalling pathways resulting in the net loss of muscle and organelles. However, the exact underpinning molecular mechanisms of how these changes are orchestrated are incompletely understood. Much work is still required, but structured exercise has the capacity to counteract numerous detrimental effects linked to cancer cachexia. Primarily through the stimulation of muscle protein synthesis, enhancement of mitochondrial function, and the release of myokines. As a result, muscle mass and strength increase, leading to improved mobility, and quality-of-life. This review summarises existing knowledge of the complex molecular networks that regulate cancer cachexia and exercise, highlighting the molecular interplay between the two for potential therapeutic intervention. Finally, the utility of mass spectrometry-based proteomics is considered as a way of establishing early diagnostic biomarkers of cachectic patients.
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Slavin MB, Khemraj P, Hood DA. Exercise, mitochondrial dysfunction and inflammasomes in skeletal muscle. Biomed J 2024; 47:100636. [PMID: 37499756 PMCID: PMC10828562 DOI: 10.1016/j.bj.2023.100636] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 07/18/2023] [Accepted: 07/20/2023] [Indexed: 07/29/2023] Open
Abstract
In the broad field of inflammation, skeletal muscle is a tissue that is understudied. Yet it represents about 40% of body mass in non-obese individuals and is therefore of fundamental importance for whole body metabolism and health. This article provides an overview of the unique features of skeletal muscle tissue, as well as its adaptability to exercise. This ability to adapt, particularly with respect to mitochondrial content and function, confers a level of metabolic "protection" against energy consuming events, and adds a measure of quality control that determines the phenotypic response to stress. Thus, we describe the particular role of mitochondria in promoting inflammasome activation in skeletal muscle, contributing to muscle wasting and dysfunction in aging, disuse and metabolic disease. We will then discuss how exercise training can be anti-inflammatory, mitigating the chronic inflammation that is observed in these conditions, potentially through improvements in mitochondrial quality and function.
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Affiliation(s)
- Mikhaela B Slavin
- School of Kinesiology and Health Science, Muscle Health Research Centre, York University, Toronto, ON, M3J 1P3, Canada
| | - Priyanka Khemraj
- School of Kinesiology and Health Science, Muscle Health Research Centre, York University, Toronto, ON, M3J 1P3, Canada
| | - David A Hood
- School of Kinesiology and Health Science, Muscle Health Research Centre, York University, Toronto, ON, M3J 1P3, Canada.
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Halle JL, Counts BR, Zhang Q, James KM, Puppa MJ, Alway SE, Carson JA. Mouse skeletal muscle adaptations to different durations of treadmill exercise after the cessation of FOLFOX chemotherapy. Front Physiol 2023; 14:1283674. [PMID: 38028800 PMCID: PMC10648895 DOI: 10.3389/fphys.2023.1283674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Accepted: 10/18/2023] [Indexed: 12/01/2023] Open
Abstract
FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) chemotherapy is a treatment for colorectal cancer that can induce persistent fatigue and metabolic dysfunction. Regular exercise after chemotherapy cessation is widely recommended for cancer patients and has been shown to improve fatigue resistance in mice. However, gaps remain in understanding whether the early systemic and skeletal muscle adaptations to regular exercise are altered by prior FOLFOX chemotherapy treatment. Furthermore, the effects of exercise duration on early metabolic and skeletal muscle transcriptional adaptations are not fully established. Purpose: Investigate the effects of prior FOLFOX chemotherapy treatment on the early adaptations to repeated short- or long-duration treadmill exercise, including the fasting regulation of circulating metabolic regulators, skeletal muscle COXIV activity and myokine/exerkine gene expression in male mice. Methods: Male C57BL6/J mice completed 4 cycles of FOLFOX or PBS and were allowed to recover for 4-weeks. Subsets of mice performed 14 sessions (6 d/wk, 18 m/min, 5% grade) of short- (10 min/d) or long-duration (55 min/d) treadmill exercise. Blood plasma and muscle tissues were collected 48-72 h after the last exercise bout for biochemical analyses. Results: Long-duration exercise increased fasting plasma osteocalcin, LIF, and IL-6 in healthy PBS mice, and these changes were ablated by prior FOLFOX treatment. Slow-oxidative soleus muscle COXIV activity increased in response to long-duration exercise in PBS mice, which was blocked by prior FOLFOX treatment. Fast-glycolytic plantaris muscle COXIV activity increased with short-duration exercise independent of FOLFOX administration. There was a main effect for long-duration exercise to increase fasting muscle IL-6 and COXIV mRNA expression independent of FOLFOX. FOLFOX administration reduced muscle IL-6, LIF, and BDNF mRNA expression irrespective of long-duration exercise. Interestingly, short-duration exercise suppressed the FOLXOX induction of muscle myostatin mRNA expression. Conclusion: FOLFOX attenuated early exercise adaptations related to fasting circulating osteocalcin, LIF, and IL-6. However, prior FOLFOX treatment did not alter the exercise adaptations of plantaris muscle COXIV activity and plasma adiponectin. An improved understanding of mechanisms underlying exercise adaptations after chemotherapy will provide the basis for successfully treating fatigue and metabolic dysfunction in cancer survivors.
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Affiliation(s)
- Jessica L. Halle
- Integrative Muscle Biology Laboratory, Division of Regenerative and Rehabilitative Sciences, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Brittany R. Counts
- Integrative Muscle Biology Laboratory, Division of Regenerative and Rehabilitative Sciences, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Quan Zhang
- Integrative Muscle Biology Laboratory, Division of Regenerative and Rehabilitative Sciences, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Kylie M. James
- Integrative Muscle Biology Laboratory, Division of Regenerative and Rehabilitative Sciences, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Melissa J. Puppa
- The University of Memphis, College of Health Sciences, Memphis, TN, United States
| | - Stephen E. Alway
- Laboratory of Muscle Biology and Sarcopenia, Department of Physical Therapy, University of Tennessee Health Science Center, Memphis, TN, United States
| | - James A. Carson
- Integrative Muscle Biology Laboratory, Division of Regenerative and Rehabilitative Sciences, University of Tennessee Health Science Center, Memphis, TN, United States
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El-Ghazali HM, Abdelbaset-Ismail A, Goda NIA, Aref M. Morphological, radiographic, three-dimensional computed tomographic, and histological features of the primary upstroke and downstroke muscles and bones in the domestic duck (Anas platyrhynchos domesticus) and the cattle egret (Bubulcus ibis, Linnaeus, 1758), reflecting the evolutionary transition towards the irreversible flightlessness. BMC Vet Res 2023; 19:133. [PMID: 37626319 PMCID: PMC10464456 DOI: 10.1186/s12917-023-03649-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 07/12/2023] [Indexed: 08/27/2023] Open
Abstract
BACKGROUND The purpose of this study was to explore whether domestication could lead to evolutionary changes towards flightlessness in the domestic duck (Anas platyrhynchos domesticus) compared to the cattle egret (Bubulcus ibis) as a nonflying and flying biological model, respectively. Bones of the pectoral girdle (scapula, clavicle, and coracoid) and the foramen triosseum were comparatively assessed using anatomical, radiographic, and 3D computed tomographic (CT) studies. Additionally, the muscles pectoralis and the supracoracoideus were histologically and immunohistochemically assessed. RESULTS Among the differences observed, radiographically, the distance between the paired clavicles was significantly wider (p < 0.05) in the domestic duck (mean ± SD 1.43 ± 0.23 cm) compared with the cattle egret (0.96 ± 0.13 cm). Unlike cattle egrets, there was no connection between the sternum and the hypocladium of furcula in domestic ducks. The scapula, clavicle, coracoid, sternum, and humerus were considerably longer in domestic ducks than in cattle egrets. The foramen triosseum appeared significantly (p < 0.01) wider in domestic ducks (0.7 ± 1.17 cm) compared to cattle egrets (0.49 ± 0.03 cm). Histologically, compared to cattle egrets, the muscle fibers in domestic ducks were loosely connected and contained fewer nuclei and perimysial/endomysial spaces. A higher myoglobin expression was evident in cattle egrets compared with domestic ducks. CONCLUSIONS Results of this study indicate that the bones and muscles of the pectoral girdle generally show specific morphological and structural changes reflective of the loss of prerequisites associated with flight behavior in domestic ducks due to domestication effects compared to cattle egrets.
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Affiliation(s)
- Hanaa M El-Ghazali
- Anatomy and Embryology Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, El-Sharkia, Egypt
| | - Ahmed Abdelbaset-Ismail
- Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, El-Sharkia, Egypt.
| | - Nehal I A Goda
- Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, El-Sharkia, Egypt
| | - Mohamed Aref
- Anatomy and Embryology Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, El-Sharkia, Egypt
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Pedersen ZO, Pedersen BS, Larsen S, Dysgaard T. A Scoping Review Investigating the "Gene-Dosage Theory" of Mitochondrial DNA in the Healthy Skeletal Muscle. Int J Mol Sci 2023; 24:8154. [PMID: 37175862 PMCID: PMC10179410 DOI: 10.3390/ijms24098154] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 04/29/2023] [Accepted: 04/30/2023] [Indexed: 05/15/2023] Open
Abstract
This review provides an overview of the evidence regarding mtDNA and valid biomarkers for assessing mitochondrial adaptions. Mitochondria are small organelles that exist in almost all cells throughout the human body. As the only organelle, mitochondria contain their own DNA, mitochondrial DNA (mtDNA). mtDNA-encoded polypeptides are subunits of the enzyme complexes in the electron transport chain (ETC) that are responsible for production of ATP to the cells. mtDNA is frequently used as a biomarker for mitochondrial content, since changes in mitochondrial volume are thought to induce similar changes in mtDNA. However, some exercise studies have challenged this "gene-dosage theory", and have indicated that changes in mitochondrial content can adapt without changes in mtDNA. Thus, the aim of this scoping review was to summarize the studies that used mtDNA as a biomarker for mitochondrial adaptions and address the question as to whether changes in mitochondrial content, induce changes in mtDNA in response to aerobic exercise in the healthy skeletal muscle. The literature was searched in PubMed and Embase. Eligibility criteria included: interventional study design, aerobic exercise, mtDNA measurements reported pre- and postintervention for the healthy skeletal muscle and English language. Overall, 1585 studies were identified. Nine studies were included for analysis. Eight out of the nine studies showed proof of increased oxidative capacity, six found improvements in mitochondrial volume, content and/or improved mitochondrial enzyme activity and seven studies did not find evidence of change in mtDNA copy number. In conclusion, the findings imply that mitochondrial adaptions, as a response to aerobic exercise, can occur without a change in mtDNA copy number.
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Affiliation(s)
- Zandra Overgaard Pedersen
- Copenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark
- Steno Diabetes Center Copenhagen, 2730 Herlev, Denmark
| | - Britt Staevnsbo Pedersen
- Copenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark
| | - Steen Larsen
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
- Clinical Research Centre, Medical University of Bialystok, 15-089 Bialystok, Poland
| | - Tina Dysgaard
- Copenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark
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Chiang M, Shih L, Lu C, Fang S. The COVID-19 vaccine did not affect the basal immune response and menstruation in female athletes. Physiol Rep 2023; 11:e15556. [PMID: 36750121 PMCID: PMC9904960 DOI: 10.14814/phy2.15556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/06/2022] [Accepted: 12/14/2022] [Indexed: 06/18/2023] Open
Abstract
The COVID-19 pandemic restricted the regular training and competition program of athletes. Vaccines against COVID-19 are known to be beneficial for the disease; however, the unknown side effects of vaccines and postvaccination reactions have made some athletes hesitant to get vaccinated. We investigated the changes in inflammatory responses and menstrual cycles of female athletes before and after vaccination. Twenty female athletes were enrolled in this study. Blood was collected from each subject before the first COVID-19 vaccination and after the first and second vaccinations. Laboratory data, including white blood cell, neutrophil, lymphocyte, and platelet counts, and inflammatory markers, including NLR (neutrophil-to-lymphocyte ratio), PLR (platelet lymphocyte ratio), RPR (red cell distribution width to platelet ratio), SII (systemic immune-inflammation index), and NeuPla (neutrophil-platelet ratio), were analyzed statistically. The menstrual changes before and after vaccination and the side effects were collected by questionnaires. No significant changes in the laboratory data were found after the first and second shots when compared to those at prevaccination: white blood cell, neutrophil, lymphocyte, platelet, NLR, PLR, SII, RPR, and NeuPla (p > 0.05). In addition, there were no significant changes in the menstruation cycle or days of the menstrual period (p > 0.05). All side effects after vaccination were mild and subsided in 2 days. The blood cell counts, inflammatory markers, and menstruation of female athletes were not affected by COVID-19 vaccines.
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Affiliation(s)
- Ming‐Ru Chiang
- Department of PediatricsJen‐Ai HospitalTaichungTaiwan
- Department of Exercise Health ScienceNational Taiwan University of SportTaichungTaiwan
| | - Li‐Chun Shih
- Department of Obstetrics and Gynecology, Puli BranchTaichung Veterans General HospitalNantouTaiwan
| | - Chi‐Cheng Lu
- Institute of AthleticsNational Taiwan University of SportTaichungTaiwan
| | - Shih‐Hua Fang
- Institute of AthleticsNational Taiwan University of SportTaichungTaiwan
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13
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Structural functionality of skeletal muscle mitochondria and its correlation with metabolic diseases. Clin Sci (Lond) 2022; 136:1851-1871. [PMID: 36545931 DOI: 10.1042/cs20220636] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 11/29/2022] [Accepted: 11/30/2022] [Indexed: 12/24/2022]
Abstract
The skeletal muscle is one of the largest organs in the mammalian body. Its remarkable ability to swiftly shift its substrate selection allows other organs like the brain to choose their preferred substrate first. Healthy skeletal muscle has a high level of metabolic flexibility, which is reduced in several metabolic diseases, including obesity and Type 2 diabetes (T2D). Skeletal muscle health is highly dependent on optimally functioning mitochondria that exist in a highly integrated network with the sarcoplasmic reticulum and sarcolemma. The three major mitochondrial processes: biogenesis, dynamics, and mitophagy, taken together, determine the quality of the mitochondrial network in the muscle. Since muscle health is primarily dependent on mitochondrial status, the mitochondrial processes are very tightly regulated in the skeletal muscle via transcription factors like peroxisome proliferator-activated receptor-γ coactivator-1α, peroxisome proliferator-activated receptors, estrogen-related receptors, nuclear respiratory factor, and Transcription factor A, mitochondrial. Physiological stimuli that enhance muscle energy expenditure, like cold and exercise, also promote a healthy mitochondrial phenotype and muscle health. In contrast, conditions like metabolic disorders, muscle dystrophies, and aging impair the mitochondrial phenotype, which is associated with poor muscle health. Further, exercise training is known to improve muscle health in aged individuals or during the early stages of metabolic disorders. This might suggest that conditions enhancing mitochondrial health can promote muscle health. Therefore, in this review, we take a critical overview of current knowledge about skeletal muscle mitochondria and the regulation of their quality. Also, we have discussed the molecular derailments that happen during various pathophysiological conditions and whether it is an effect or a cause.
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14
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Martel-Pelletier J, Pelletier JP. Is there a mitochondrial DNA haplogroup connection between osteoarthritis and elite athletes? A narrative review. RMD Open 2022; 8:rmdopen-2022-002602. [PMID: 36113964 PMCID: PMC9486370 DOI: 10.1136/rmdopen-2022-002602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 09/06/2022] [Indexed: 11/04/2022] Open
Abstract
Elite athletes are at greater risk of joint injuries linked to the subsequent risk of developing osteoarthritis (OA). Genetic factors such as mitochondrial (mt) DNA haplogroups have been associated with the incidence/progression of OA and athletic performance. This review highlights an area not yet addressed: is there a common pattern in the mtDNA haplogroups for OA occurrence in individuals and elite athletes of populations of the same descent? Haplotypes J and T confer a decreased risk of OA in Caucasian/European descent, while H and U increase this risk. Both J and T haplogroups are under-represented in Caucasian/European individuals and endurance athletes with OA, but power athletes showed a greater percentage of the J haplogroup. Caucasian/European endurance athletes had a higher percentage of haplogroup H, which is associated with increased athletic performance. In a Chinese population, haplogroup G appears to increase OA susceptibility and is over-represented in Japanese endurance athletes. In contrast, in Koreans, haplogroup B had a higher frequency of individuals with OA but was under-represented in the endurance athlete population. For Caucasian endurance athletes, it would be interesting to evaluate if those carrying haplotype H would be at an increased risk of accelerated OA, as well as the haplogroup G in Chinese and Japanese endurance athletes. The reverse might be studied for the Korean descent for haplogroup B. Knowledge of such genetic data could be used as a preliminary diagnosis to identify individuals at high risk of OA, adding prognostic information and assisting in personalising the early management of both populations.
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Affiliation(s)
- Johanne Martel-Pelletier
- Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada
| | - Jean-Pierre Pelletier
- Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada
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15
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Localized Heat Therapy Improves Mitochondrial Respiratory Capacity but Not Fatty Acid Oxidation. Int J Mol Sci 2022; 23:ijms23158500. [PMID: 35955635 PMCID: PMC9369322 DOI: 10.3390/ijms23158500] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 07/26/2022] [Accepted: 07/28/2022] [Indexed: 11/26/2022] Open
Abstract
AIM: Mild heat stress can improve mitochondrial respiratory capacity in skeletal muscle. However, long-term heat interventions are scarce, and the effects of heat therapy need to be understood in the context of the adaptations which follow the more complex combination of stimuli from exercise training. The purpose of this work was to compare the effects of 6 weeks of localized heat therapy on human skeletal muscle mitochondria to single-leg interval training. METHODS: Thirty-five subjects were assigned to receive sham therapy, short-wave diathermy heat therapy, or single-leg interval exercise training, localized to the quadriceps muscles of the right leg. All interventions took place 3 times per week. Muscle biopsies were performed at baseline, and after 3 and 6 weeks of intervention. Mitochondrial respiratory capacity was assessed on permeabilized muscle fibers via high-resolution respirometry. RESULTS: The primary finding of this work was that heat therapy and exercise training significantly improved mitochondrial respiratory capacity by 24.8 ± 6.2% and 27.9 ± 8.7%, respectively (p < 0.05). Fatty acid oxidation and citrate synthase activity were also increased following exercise training by 29.5 ± 6.8% and 19.0 ± 7.4%, respectively (p < 0.05). However, contrary to our hypothesis, heat therapy did not increase fatty acid oxidation or citrate synthase activity. CONCLUSION: Six weeks of muscle-localized heat therapy significantly improves mitochondrial respiratory capacity, comparable to exercise training. However, unlike exercise, heat does not improve fatty acid oxidation capacity.
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16
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Collins KA, Ross LM, Slentz CA, Huffman KM, Kraus WE. Differential Effects of Amount, Intensity, and Mode of Exercise Training on Insulin Sensitivity and Glucose Homeostasis: A Narrative Review. SPORTS MEDICINE - OPEN 2022; 8:90. [PMID: 35834023 PMCID: PMC9283590 DOI: 10.1186/s40798-022-00480-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 06/18/2022] [Indexed: 11/29/2022]
Abstract
As type 2 diabetes remains a leading cause of morbidity and mortality, identifying the most appropriate preventive treatment early in the development of disease is an important public health matter. In general, lifestyle interventions incorporating exercise and weight loss via caloric restriction improve cardiometabolic risk by impacting several key markers of insulin sensitivity and glucose homeostasis. However, variations in the effects of specific types of exercise interventions on these markers have led to conflicting results surrounding the optimal amount, intensity, and mode of exercise for optimal effects. Moreover, the addition of weight loss via caloric restriction to exercise interventions appears to differentially impact changes in body composition, metabolism, and insulin sensitivity compared to exercise alone. Determining the optimal amount, intensity, and mode of exercise having the most beneficial impact on glycemic status is both: (1) clinically important to provide guidelines for appropriate exercise prescription; and (2) physiologically important to understand the pathways by which exercise-with and without weight loss-impacts glycemic status to enhance precision lifestyle medicine. Thus, the purposes of this narrative review are to: (1) summarize findings from the three Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) randomized trials regarding the differential effects of exercise amount, intensity, and mode on insulin action and glucose homeostasis markers; and (2) compare the STRRIDE findings to other published dose-response exercise trials in order to piece together the various physiologic pathways by which specific exercise interventions-with or without weight loss-impact glycemic status.
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Affiliation(s)
- Katherine A Collins
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA
| | - Leanna M Ross
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.
| | - Cris A Slentz
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA
| | - Kim M Huffman
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA
| | - William E Kraus
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA
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17
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Tripp TR, Frankish BP, Lun V, Wiley JP, Shearer J, Murphy RM, MacInnis MJ. Time course and fibre type-dependent nature of calcium-handling protein responses to sprint interval exercise in human skeletal muscle. J Physiol 2022; 600:2897-2917. [PMID: 35556249 DOI: 10.1113/jp282739] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 04/22/2022] [Indexed: 11/08/2022] Open
Abstract
KEY POINTS Sprint interval training (SIT) has been shown to cause fragmentation of the sarcoplasmic reticulum calcium-release channel, ryanodine receptor 1 (RyR1) 24 hours post-exercise, which may act as a signal for mitochondrial biogenesis. In this study, we examined the time course of RyR1 fragmentation in human whole muscle and pooled type I and type II skeletal muscle fibres following a single session of SIT. Full-length RyR1 protein content was significantly lower than pre-exercise by 6 h post-SIT in whole muscle, and fragmentation was detectable in type II but not type I fibres, though to a lesser extent than in whole muscle. The peak in PGC1A mRNA expression occurred earlier than RyR1 fragmentation. The increased temporal resolution and fibre type-specific responses for RyR1 fragmentation provide insights into its importance to mitochondrial biogenesis in humans. ABSTRACT Sprint interval training (SIT) causes fragmentation of the skeletal muscle sarcoplasmic reticulum Ca2+ release channel, ryanodine receptor 1 (RyR1), 24h post-exercise, potentially signaling mitochondrial biogenesis by increasing cytosolic [Ca2+ ]. Yet, the time course and skeletal muscle fibre type-specific patterns of RyR1 fragmentation following a session of SIT remain unknown. Ten participants (n = 4 females; n = 6 males) performed a session of SIT (6 × 30 s "all-out" with 4.5 min rest after each sprint) with vastus lateralis muscle biopsy samples collected before and 3, 6, and 24h after exercise. In whole muscle, full-length RyR1 protein content was significantly reduced 6 h (mean [SD]; -38 [38]%; p<0.05) and 24 h post-SIT (-30 [48]%; p<0.05) compared to pre-exercise. Examining each participant's largest response in pooled samples, full-length RyR1 protein content was reduced in type II (-26 [30]%; p<0.05) but not type I fibres (-11 [40]%; p>0.05). 3h post-SIT, there was also a decrease in SERCA1 in type II fibres (-23 [17]%; p<0.05) and SERCA2a in type I fibres (-19 [21]%; p<0.05), despite no time effect for either protein in whole muscle samples (p>0.05). PGC1A mRNA content was elevated 3h and 6h post-SIT (5.3- and 3.7-fold change from pre, respectively; p<0.05 for both), but peak PGC1A mRNA expression was not significantly correlated with peak RyR1 fragmentation (r2 = 0.10; p>0.05). In summary, altered Ca2+ -handling protein expression, which occurs primarily in type II muscle fibres, may influence signals for mitochondrial biogenesis as early as 3-6 h post-SIT in humans. Abstract figure legend Western blotting was performed on whole muscle and pooled type I and II muscle fibre preparations derived from human vastus lateralis muscle biopsy samples collected before and after a single session of sprint interval training (SIT). Full-length ryanodine receptor 1 (RyR1) protein content was reduced 6 and 24 h post-exercise in whole muscle samples compared to baseline, despite a heterogeneous time course among individuals. This RyR1 fragmentation proceeded and outlasted the increase in peroxisome proliferator-activated γ receptor coactivator 1α (PGC1A) mRNA expression. When examining the time point of each individual's peak response, RyR1 fragmentation was evident in type II, but not type I, muscle fibres. These findings suggest that, in humans, mitochondrial biogenesis could be influenced by RyR1 fragmentation 3-6 h post-SIT in a fibre type-dependent manner. Created with BioRender.com. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Thomas R Tripp
- Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
| | - Barnaby P Frankish
- Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.,Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Australia
| | - Victor Lun
- University of Calgary Sport Medicine Centre, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
| | - J Preston Wiley
- Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.,University of Calgary Sport Medicine Centre, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
| | - Jane Shearer
- Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.,Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Robyn M Murphy
- Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, Australia
| | - Martin J MacInnis
- Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
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18
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Husak JF, Lailvaux SP. Conserved and convergent mechanisms underlying performance-life-history trade-offs. J Exp Biol 2022; 225:274252. [PMID: 35119073 DOI: 10.1242/jeb.243351] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Phenotypic trade-offs are inevitable in nature, but the mechanisms driving them are poorly understood. Movement and oxygen are essential to all animals, and as such, the common ancestor to all living animals passed on mechanisms to acquire oxygen and contract muscle, sometimes at the expense of other activities or expression of traits. Nevertheless, convergent pathways have also evolved to deal with critical trade-offs that are necessary to survive ubiquitous environmental challenges. We discuss how whole-animal performance traits, such as locomotion, are important to fitness, yet costly, resulting in trade-offs with other aspects of the phenotype via specific conserved and convergent mechanistic pathways across all animals. Specifically, we discuss conserved pathways involved in muscle structure and signaling, insulin/insulin-like signaling, sirtuins, mitochondria and hypoxia-inducible factors, as well as convergent pathways involved in energy regulation, development, reproductive investment and energy storage. The details of these mechanisms are only known from a few model systems, and more comparative studies are needed. We make two main recommendations as a framework for future studies of animal form and function. First, studies of performance should consider the broader life-history context of the organism, and vice versa, as performance expression can require a large portion of acquired resources. Second, studies of life histories or mechanistic pathways that measure performance should do so in meaningful and standardized ways. Understanding proximate mechanisms of phenotypic trade-offs will not only better explain the phenotypes of the organisms we study, but also allow predictions about phenotypic variation at the evolutionary scale.
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Affiliation(s)
- Jerry F Husak
- Department of Biology, University of St. Thomas, St. Paul, MN 55105, USA
| | - Simon P Lailvaux
- Department of Biological Sciences, University of New Orleans, New Orleans, LA 70148, USA
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19
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Zhang X, Gao F. Exercise improves vascular health: Role of mitochondria. Free Radic Biol Med 2021; 177:347-359. [PMID: 34748911 DOI: 10.1016/j.freeradbiomed.2021.11.002] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 10/20/2021] [Accepted: 11/02/2021] [Indexed: 01/10/2023]
Abstract
Vascular mitochondria constantly integrate signals from environment and respond accordingly to match vascular function to metabolic requirements of the organ tissues, while mitochondrial dysfunction contributes to vascular aging and pathologies such as atherosclerosis, stenosis, and hypertension. As an effective lifestyle intervention, exercise induces extensive mitochondrial adaptations through vascular mechanical stress and the increased production and release of reactive oxygen species and nitric oxide that activate multiple intracellular signaling pathways, among which peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) plays a critical role. PGC-1α coordinates mitochondrial quality control mechanisms to maintain a healthy mitochondrial pool and promote endothelial nitric oxide synthase activity in vasculature. The mitochondrial adaptations to exercise improve bioenergetics, balance redox status, protect endothelial cells against detrimental insults, increase vascular plasticity, and ameliorate aging-related vascular dysfunction, thus benefiting vascular health. This review highlights recent findings of mitochondria as a central hub integrating exercise-afforded vascular benefits and its underlying mechanisms. A better understanding of the mitochondrial adaptations to exercise will not only shed light on the mechanisms of exercise-induced cardiovascular protection, but may also provide new clues to mitochondria-oriented precise exercise prescriptions for cardiovascular health.
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Affiliation(s)
- Xing Zhang
- Key Laboratory of Aerospace Medicine of the Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032, China.
| | - Feng Gao
- Key Laboratory of Aerospace Medicine of the Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032, China.
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20
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Vargas-Mendoza N, Angeles-Valencia M, Morales-González Á, Madrigal-Santillán EO, Morales-Martínez M, Madrigal-Bujaidar E, Álvarez-González I, Gutiérrez-Salinas J, Esquivel-Chirino C, Chamorro-Cevallos G, Cristóbal-Luna JM, Morales-González JA. Oxidative Stress, Mitochondrial Function and Adaptation to Exercise: New Perspectives in Nutrition. Life (Basel) 2021; 11:1269. [PMID: 34833151 PMCID: PMC8624755 DOI: 10.3390/life11111269] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 11/10/2021] [Accepted: 11/13/2021] [Indexed: 02/07/2023] Open
Abstract
Cells have the ability to adapt to stressful environments as a part of their evolution. Physical exercise induces an increase of a demand for energy that must be met by mitochondria as the main (ATP) provider. However, this process leads to the increase of free radicals and the so-called reactive oxygen species (ROS), which are necessary for the maintenance of cell signaling and homeostasis. In addition, mitochondrial biogenesis is influenced by exercise in continuous crosstalk between the mitochondria and the nuclear genome. Excessive workloads may induce severe mitochondrial stress, resulting in oxidative damage. In this regard, the objective of this work was to provide a general overview of the molecular mechanisms involved in mitochondrial adaptation during exercise and to understand if some nutrients such as antioxidants may be implicated in blunt adaptation and/or an impact on the performance of exercise by different means.
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Affiliation(s)
- Nancy Vargas-Mendoza
- Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Col. Casco de Santo Tomás, Del. Miguel Hidalgo, Ciudad de México 11340, Mexico; (N.V.-M.); (M.A.-V.); (E.O.M.-S.)
| | - Marcelo Angeles-Valencia
- Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Col. Casco de Santo Tomás, Del. Miguel Hidalgo, Ciudad de México 11340, Mexico; (N.V.-M.); (M.A.-V.); (E.O.M.-S.)
| | - Ángel Morales-González
- Escuela Superior de Cómputo, Instituto Politécnico Nacional, Av. Juan de Dios Bátiz s/n Esquina Miguel Othón de Mendizabal, Unidad Profesional Adolfo López Mateos, Ciudad de México 07738, Mexico
| | - Eduardo Osiris Madrigal-Santillán
- Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Col. Casco de Santo Tomás, Del. Miguel Hidalgo, Ciudad de México 11340, Mexico; (N.V.-M.); (M.A.-V.); (E.O.M.-S.)
| | - Mauricio Morales-Martínez
- Licenciatura en Nutrición, Universidad Intercontinental, Insurgentes Sur 4303, Santa Úrsula Xitla, Alcaldía Tlalpan, Ciudad de México 14420, Mexico;
| | - Eduardo Madrigal-Bujaidar
- Laboratorio de Genética, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Unidad Profesional A. López Mateos, Av. Wilfrido Massieu, Col., Lindavista, Ciudad de México 07738, Mexico; (E.M.-B.); (I.Á.-G.)
| | - Isela Álvarez-González
- Laboratorio de Genética, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Unidad Profesional A. López Mateos, Av. Wilfrido Massieu, Col., Lindavista, Ciudad de México 07738, Mexico; (E.M.-B.); (I.Á.-G.)
| | - José Gutiérrez-Salinas
- Laboratorio de Bioquímica y Medicina Experimental, Centro Médico Nacional “20 de Noviembre”, ISSSTE, Ciudad de México 03229, Mexico;
| | - César Esquivel-Chirino
- Área de Básicas Médicas, División de Estudios Profesionales, Facultad de Odontología, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico;
| | - Germán Chamorro-Cevallos
- Laboratorio de Toxicología Preclínica, Departamento de Farmacia, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Av. Wilfrido Massieu 399, Col. Nueva Industrial Vallejo, Del. Gustavo A. Madero, Ciudad de México 07738, Mexico; (G.C.-C.); (J.M.C.-L.)
| | - José Melesio Cristóbal-Luna
- Laboratorio de Toxicología Preclínica, Departamento de Farmacia, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Av. Wilfrido Massieu 399, Col. Nueva Industrial Vallejo, Del. Gustavo A. Madero, Ciudad de México 07738, Mexico; (G.C.-C.); (J.M.C.-L.)
| | - José A. Morales-González
- Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Col. Casco de Santo Tomás, Del. Miguel Hidalgo, Ciudad de México 11340, Mexico; (N.V.-M.); (M.A.-V.); (E.O.M.-S.)
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Pohl A, Schünemann F, Bersiner K, Gehlert S. The Impact of Vegan and Vegetarian Diets on Physical Performance and Molecular Signaling in Skeletal Muscle. Nutrients 2021; 13:3884. [PMID: 34836139 PMCID: PMC8623732 DOI: 10.3390/nu13113884] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 10/27/2021] [Accepted: 10/28/2021] [Indexed: 12/12/2022] Open
Abstract
Muscular adaptations can be triggered by exercise and diet. As vegan and vegetarian diets differ in nutrient composition compared to an omnivorous diet, a change in dietary regimen might alter physiological responses to physical exercise and influence physical performance. Mitochondria abundance, muscle capillary density, hemoglobin concentration, endothelial function, functional heart morphology and availability of carbohydrates affect endurance performance and can be influenced by diet. Based on these factors, a vegan and vegetarian diet possesses potentially advantageous properties for endurance performance. Properties of the contractile elements, muscle protein synthesis, the neuromuscular system and phosphagen availability affect strength performance and can also be influenced by diet. However, a vegan and vegetarian diet possesses potentially disadvantageous properties for strength performance. Current research has failed to demonstrate consistent differences of performance between diets but a trend towards improved performance after vegetarian and vegan diets for both endurance and strength exercise has been shown. Importantly, diet alters molecular signaling via leucine, creatine, DHA and EPA that directly modulates skeletal muscle adaptation. By changing the gut microbiome, diet can modulate signaling through the production of SFCA.
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Affiliation(s)
- Alexander Pohl
- Department of Biosciences of Sport Science, Institute of Sport Science, University of Hildesheim, 31141 Hildesheim, Germany; (F.S.); (K.B.); (S.G.)
| | - Frederik Schünemann
- Department of Biosciences of Sport Science, Institute of Sport Science, University of Hildesheim, 31141 Hildesheim, Germany; (F.S.); (K.B.); (S.G.)
| | - Käthe Bersiner
- Department of Biosciences of Sport Science, Institute of Sport Science, University of Hildesheim, 31141 Hildesheim, Germany; (F.S.); (K.B.); (S.G.)
| | - Sebastian Gehlert
- Department of Biosciences of Sport Science, Institute of Sport Science, University of Hildesheim, 31141 Hildesheim, Germany; (F.S.); (K.B.); (S.G.)
- Department for Molecular and Cellular Sports Medicine, German Sports University Cologne, 50933 Cologne, Germany
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22
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Aerobic Exercise Induces Alternative Splicing of Neurexins in Frontal Cortex. J Funct Morphol Kinesiol 2021; 6:jfmk6020048. [PMID: 34072692 PMCID: PMC8261640 DOI: 10.3390/jfmk6020048] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/24/2021] [Accepted: 05/26/2021] [Indexed: 12/02/2022] Open
Abstract
Aerobic exercise (AE) is known to produce beneficial effects on brain health by improving plasticity, connectivity, and cognitive functions, but the underlying molecular mechanisms are still limited. Neurexins (Nrxns) are a family of presynaptic cell adhesion molecules that are important in synapsis formation and maturation. In vertebrates, three-neurexin genes (NRXN1, NRXN2, and NRXN3) have been identified, each encoding for α and β neurexins, from two independent promoters. Moreover, each Nrxns gene (1-3) has several alternative exons and produces many splice variants that bind to a large variety of postsynaptic ligands, playing a role in trans-synaptic specification, strength, and plasticity. In this study, we investigated the impact of a continuous progressive (CP) AE program on alternative splicing (AS) of Nrxns on two brain regions: frontal cortex (FC) and hippocampus. We showed that exercise promoted Nrxns1-3 AS at splice site 4 (SS4) both in α and β isoforms, inducing a switch from exon-excluded isoforms (SS4-) to exon-included isoforms (SS4+) in FC but not in hippocampus. Additionally, we showed that the same AE program enhanced the expression level of other genes correlated with synaptic function and plasticity only in FC. Altogether, our findings demonstrated the positive effect of CP AE on FC in inducing molecular changes underlying synaptic plasticity and suggested that FC is possibly a more sensitive structure than hippocampus to show molecular changes.
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Thoral E, Queiros Q, Roussel D, Dutto G, Gasset E, McKenzie DJ, Romestaing C, Fromentin JM, Saraux C, Teulier L. Changes in foraging mode caused by a decline in prey size have major bioenergetic consequences for a small pelagic fish. J Anim Ecol 2021; 90:2289-2301. [PMID: 34013518 DOI: 10.1111/1365-2656.13535] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 05/10/2021] [Indexed: 12/13/2022]
Abstract
Global warming is causing profound modifications of aquatic ecosystems and one major outcome appears to be a decline in adult size of many fish species. Over the last decade, sardine populations in the Gulf of Lions (NW Mediterranean Sea) have shown severe declines in body size and condition as well as disappearance of the oldest individuals, which could not be related to overfishing, predation pressure or epizootic diseases. In this study, we investigated whether this situation reflects a bottom-up phenomenon caused by reduced size and availability of prey that could lead to energetic constraints. We fed captive sardines with food items of two different sizes eliciting a change in feeding mode (filter-feeding on small items and directly capturing larger ones) at two different rations for several months, and then assessed their muscle bioenergetics to test for changes in cellular function. Feeding on smaller items was associated with a decline in body condition, even at high ration, and almost completely inhibited growth by comparison to sardines fed large items at high ration. Sardines fed on small items presented specific mitochondrial adjustments for energy sparing, indicating a major bioenergetic challenge. Moreover, mitochondria from sardines in poor condition had low basal oxidative activity but high efficiency of ATP production. Notably, when body condition was below a threshold value of 1.07, close to the mean observed in the wild, it was directly correlated with basal mitochondrial activity in muscle. The results show a link between whole-animal condition and cellular bioenergetics in the sardine, and reveal physiological consequences of a shift in feeding mode. They demonstrate that filter-feeding on small prey leads to poor growth, even under abundant food and an increase in the efficiency of ATP production. These findings may partially explain the declines in sardine size and condition observed in the wild.
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Affiliation(s)
- Elisa Thoral
- Univ Lyon, Université Claude Bernard Lyon 1, CNRS, ENTPE, UMR 5023 LEHNA, Villeurbanne, France
| | | | - Damien Roussel
- Univ Lyon, Université Claude Bernard Lyon 1, CNRS, ENTPE, UMR 5023 LEHNA, Villeurbanne, France
| | - Gilbert Dutto
- Ifremer (Institut Français de Recherche pour l'Exploitation de la MER), Laboratoire SEA, Palavas-Les-Flots, France
| | - Eric Gasset
- MARBEC, Univ Montpellier, CNRS, IFREMER, IRD, Palavas-Les-Flots, France
| | - David J McKenzie
- MARBEC, Univ Montpellier, CNRS, IFREMER, IRD, Montpellier, France
| | - Caroline Romestaing
- Univ Lyon, Université Claude Bernard Lyon 1, CNRS, ENTPE, UMR 5023 LEHNA, Villeurbanne, France
| | | | - Claire Saraux
- MARBEC, Univ Montpellier, CNRS, IFREMER, IRD, Sète, France.,IPHC, UMR7178, Université de Strasbourg, CNRS, Strasbourg, France
| | - Loïc Teulier
- Univ Lyon, Université Claude Bernard Lyon 1, CNRS, ENTPE, UMR 5023 LEHNA, Villeurbanne, France
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24
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Avin KG, Hughes MC, Chen NX, Srinivasan S, O’Neill KD, Evan AP, Bacallao RL, Schulte ML, Moorthi RN, Gisch DL, Perry CGR, Moe SM, O’Connell TM. Skeletal muscle metabolic responses to physical activity are muscle type specific in a rat model of chronic kidney disease. Sci Rep 2021; 11:9788. [PMID: 33963215 PMCID: PMC8105324 DOI: 10.1038/s41598-021-89120-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 04/14/2021] [Indexed: 02/03/2023] Open
Abstract
Chronic kidney disease (CKD) leads to musculoskeletal impairments that are impacted by muscle metabolism. We tested the hypothesis that 10-weeks of voluntary wheel running can improve skeletal muscle mitochondria activity and function in a rat model of CKD. Groups included (n = 12-14/group): (1) normal littermates (NL); (2) CKD, and; (3) CKD-10 weeks of voluntary wheel running (CKD-W). At 35-weeks old the following assays were performed in the soleus and extensor digitorum longus (EDL): targeted metabolomics, mitochondrial respiration, and protein expression. Amino acid-related compounds were reduced in CKD muscle and not restored by physical activity. Mitochondrial respiration in the CKD soleus was increased compared to NL, but not impacted by physical activity. The EDL respiration was not different between NL and CKD, but increased in CKD-wheel rats compared to CKD and NL groups. Our results demonstrate that the soleus may be more susceptible to CKD-induced changes of mitochondrial complex content and respiration, while in the EDL, these alterations were in response the physiological load induced by mild physical activity. Future studies should focus on therapies to improve mitochondrial function in both types of muscle to determine if such treatments can improve the ability to adapt to physical activity in CKD.
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Affiliation(s)
- Keith G. Avin
- Division of Nephrology, Indiana University School of Medicine, 950 W. Walnut St., R2 202, Indianapolis, IN 46202 USA ,Department of Physical Therapy, Indiana University School of Health and Human Sciences, Indianapolis, IN USA ,Roudebush Veterans Affairs Medical Center, Indianapolis, IN USA
| | - Meghan C. Hughes
- School of Kinesiology and Health Science, Muscle Health Research Centre, York University, Toronto, ON Canada
| | - Neal X. Chen
- Division of Nephrology, Indiana University School of Medicine, 950 W. Walnut St., R2 202, Indianapolis, IN 46202 USA ,Roudebush Veterans Affairs Medical Center, Indianapolis, IN USA
| | - Shruthi Srinivasan
- Division of Nephrology, Indiana University School of Medicine, 950 W. Walnut St., R2 202, Indianapolis, IN 46202 USA ,Roudebush Veterans Affairs Medical Center, Indianapolis, IN USA
| | - Kalisha D. O’Neill
- Division of Nephrology, Indiana University School of Medicine, 950 W. Walnut St., R2 202, Indianapolis, IN 46202 USA ,Roudebush Veterans Affairs Medical Center, Indianapolis, IN USA
| | - Andrew P. Evan
- Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN USA
| | - Robert L. Bacallao
- Division of Nephrology, Indiana University School of Medicine, 950 W. Walnut St., R2 202, Indianapolis, IN 46202 USA ,Roudebush Veterans Affairs Medical Center, Indianapolis, IN USA
| | - Michael L. Schulte
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN USA
| | - Ranjani N. Moorthi
- Division of Nephrology, Indiana University School of Medicine, 950 W. Walnut St., R2 202, Indianapolis, IN 46202 USA
| | - Debora L. Gisch
- Departamento de Engenharia Mecânica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS Brazil
| | - Christopher G. R. Perry
- School of Kinesiology and Health Science, Muscle Health Research Centre, York University, Toronto, ON Canada
| | - Sharon M. Moe
- Division of Nephrology, Indiana University School of Medicine, 950 W. Walnut St., R2 202, Indianapolis, IN 46202 USA ,Roudebush Veterans Affairs Medical Center, Indianapolis, IN USA ,Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN USA
| | - Thomas M. O’Connell
- Department of Otolaryngology, Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN USA
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25
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Just-Borràs L, Cilleros-Mañé V, Hurtado E, Biondi O, Charbonnier F, Tomàs M, Garcia N, Tomàs J, Lanuza MA. Running and Swimming Differently Adapt the BDNF/TrkB Pathway to a Slow Molecular Pattern at the NMJ. Int J Mol Sci 2021; 22:4577. [PMID: 33925507 PMCID: PMC8123836 DOI: 10.3390/ijms22094577] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/22/2021] [Accepted: 04/23/2021] [Indexed: 12/29/2022] Open
Abstract
Physical exercise improves motor control and related cognitive abilities and reinforces neuroprotective mechanisms in the nervous system. As peripheral nerves interact with skeletal muscles at the neuromuscular junction, modifications of this bidirectional communication by physical activity are positive to preserve this synapse as it increases quantal content and resistance to fatigue, acetylcholine receptors expansion, and myocytes' fast-to-slow functional transition. Here, we provide the intermediate step between physical activity and functional and morphological changes by analyzing the molecular adaptations in the skeletal muscle of the full BDNF/TrkB downstream signaling pathway, directly involved in acetylcholine release and synapse maintenance. After 45 days of training at different intensities, the BDNF/TrkB molecular phenotype of trained muscles from male B6SJLF1/J mice undergo a fast-to-slow transition without affecting motor neuron size. We provide further knowledge to understand how exercise induces muscle molecular adaptations towards a slower phenotype, resistant to prolonged trains of stimulation or activity that can be useful as therapeutic tools.
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Affiliation(s)
- Laia Just-Borràs
- Unitat d’Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, 43201 Reus, Spain; (L.J.-B.); (V.C.-M.); (E.H.); (M.T.); (N.G.)
| | - Víctor Cilleros-Mañé
- Unitat d’Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, 43201 Reus, Spain; (L.J.-B.); (V.C.-M.); (E.H.); (M.T.); (N.G.)
| | - Erica Hurtado
- Unitat d’Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, 43201 Reus, Spain; (L.J.-B.); (V.C.-M.); (E.H.); (M.T.); (N.G.)
| | - Olivier Biondi
- INSERM UMRS 1124, Université de Paris, CEDEX 06, F-75270 Paris, France; (O.B.); (F.C.)
| | - Frédéric Charbonnier
- INSERM UMRS 1124, Université de Paris, CEDEX 06, F-75270 Paris, France; (O.B.); (F.C.)
| | - Marta Tomàs
- Unitat d’Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, 43201 Reus, Spain; (L.J.-B.); (V.C.-M.); (E.H.); (M.T.); (N.G.)
| | - Neus Garcia
- Unitat d’Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, 43201 Reus, Spain; (L.J.-B.); (V.C.-M.); (E.H.); (M.T.); (N.G.)
| | - Josep Tomàs
- Unitat d’Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, 43201 Reus, Spain; (L.J.-B.); (V.C.-M.); (E.H.); (M.T.); (N.G.)
| | - Maria A. Lanuza
- Unitat d’Histologia i Neurobiologia (UHNEUROB), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, 43201 Reus, Spain; (L.J.-B.); (V.C.-M.); (E.H.); (M.T.); (N.G.)
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26
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Chang YB, Hong KB, Kim MG, Suh HJ, Jo K. Effect of the protein hydrolysate of rice syrup meal on the endurance exercise performance of BALB/c mice. Food Funct 2021; 12:1338-1348. [PMID: 33448266 DOI: 10.1039/d0fo02667k] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Rice is a staple food in Korea. The protein in rice reportedly contains higher levels of branched-chain amino acids (BCAAs) than proteins in other grains. Taking BCAAs during exercise can reduce muscle fatigue by reducing muscle glycogen depletion. However, there are limited studies reporting the anti-fatigue effect of rice protein. We investigate the muscular endurance and anti-fatigue effects of the protein hydrolysate of rice syrup meal in mouse models. BALB/C mice were divided into the following groups: control (CON), low and high dose rice syrup meal (RL: 1.5 g kg-1; RH: 3.0 g kg-1), and low and high dose protein hydrolysate of rice syrup meal (PL: 1.5 g kg-1; PH: 3.0 g kg-1). The total activity during a forced swimming test was analyzed by a behavioral assay. The mutual relationship between the anti-fatigue activity and energy metabolism was assessed by biochemical, enzyme activity, and gene expression analyses. The protein hydrolysate of rice syrup meal contained 32.18 mg g-1 BCAAs, such as leucine, isoleucine, and valine, and its BCAA ratio (2.5 : 1.0 : 1.4) was considered effective for endurance exercise. Furthermore, PH administration significantly increased the change in the maximum swimming duration by 4.2 min (3.77 ± 0.74 min) compared to that of the CON group (-0.42 ± 0.55 min, p < 0.01). The PH group showed significantly different changes in the blood glucose and lactate levels compared with the CON group; similarly, the aspartate amino transferase and alanine amino transferase levels were significantly lower in the protein hydrolysate of rice syrup meal group than the CON group (p < 0.001 and p < 0.01, respectively). The protein hydrolysate of rice syrup meal-mediated improvement of endurance performance was accompanied by an increased in adenosine triphosphate content in the muscle and decreased reactive oxygen species accumulation in the liver. In addition, mRNA and protein levels of phospho-AMP activated protein kinase (p-AMPK)/AMPK and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), the major energy-related factors of protein hydrolysate of rice syrup meal, were significantly increased. The protein hydrolysate of rice syrup meal can be utilized as an efficacious natural resource for its muscular-endurance-enhancing and anti-fatigue effects.
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Affiliation(s)
- Yeok Boo Chang
- Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul 02841, Republic of Korea.
| | - Ki-Bae Hong
- Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul 02841, Republic of Korea.
| | - Min Guk Kim
- Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul 02841, Republic of Korea.
| | - Hyung Joo Suh
- Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul 02841, Republic of Korea.
| | - Kyungae Jo
- Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul 02841, Republic of Korea.
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27
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Hong CT, Hu CJ, Lin HY, Wu D. Effects of concomitant use of hydrogen water and photobiomodulation on Parkinson disease: A pilot study. Medicine (Baltimore) 2021; 100:e24191. [PMID: 33530211 PMCID: PMC7850666 DOI: 10.1097/md.0000000000024191] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Accepted: 12/11/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Parkinson disease (PD), the second most common neurodegenerative disease, has no cure or applicable disease-modifying approach, only symptomatic therapy. Oxidative stress and mitochondrial dysfunction play key roles in PD pathophysiology. Animal studies have demonstrated that photobiomodulation (PBM) may enhance mitochondrial function and boost adenosine triphosphate production, thus alleviating PD symptoms; however, this process can cause increased reactive oxygen species (ROS) production. Molecular hydrogen (H2) is a potent and possibly therapeutic antioxidant that can mitigate the effect of ROS. PBM targeting the brainstem may facilitate neuronal activity, and the concomitant H2 may clear additional ROS produced by PBM. Therefore, this study aimed to determine the safety and effectiveness of PBM + H2 in patients with PD. METHODS We included 18 patients with PD (age 30-80 years) who were at Hoehn and Yahr stages II-III. All the participants received daily PBM + H2 therapy for 2 weeks. The adverse event and the Unified Parkinson Disease Rating Scale (UPDRS) scores were recorded. RESULTS We noted that the UPDRS scores began significantly decreasing from the first week, and this improvement persisted until the end of therapy. Moreover, no adverse event was recorded. After 1 week of therapy cessation, UPDRS scores slightly increased but the improvement remained significant compared with the baseline. CONCLUSION This novel, proof-of-concept study demonstrated that PBM+H2 therapy is safe and reduces disease severity. A larger-scaled clinical trial is warranted to completely investigate the effects of PBM + H2 therapy on PD.
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Affiliation(s)
- Chien-Tai Hong
- Department of Neurology, Taipei Medical University Shuang Ho Hospital, New Taipei City
- Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University
| | - Chaur-Jong Hu
- Department of Neurology, Taipei Medical University Shuang Ho Hospital, New Taipei City
- Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University
| | - Hung-Yu Lin
- National Taipei University of Technology, Taipei, Taiwan
| | - Dean Wu
- Department of Neurology, Taipei Medical University Shuang Ho Hospital, New Taipei City
- Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University
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28
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Ferguson RA, Mitchell EA, Taylor CW, Bishop DJ, Christiansen D. Blood-flow-restricted exercise: Strategies for enhancing muscle adaptation and performance in the endurance-trained athlete. Exp Physiol 2021; 106:837-860. [PMID: 33486814 DOI: 10.1113/ep089280] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Accepted: 01/19/2021] [Indexed: 12/15/2022]
Abstract
NEW FINDINGS What is the topic of this review? Blood-flow-restricted (BFR) exercise represents a potential approach to augment the adaptive response to training and improve performance in endurance-trained individuals. What advances does it highlight? When combined with low-load resistance exercise, low- and moderate-intensity endurance exercise and sprint interval exercise, BFR can provide an augmented acute stimulus for angiogenesis and mitochondrial biogenesis. These augmented acute responses can translate into enhanced capillary supply and mitochondrial function, and subsequent endurance-type performance, although this might depend on the nature of the exercise stimulus. There is a requirement to clarify whether BFR training interventions can be used by high-performance endurance athletes within their structured training programme. ABSTRACT A key objective of the training programme for an endurance athlete is to optimize the underlying physiological determinants of performance. Training-induced adaptations are governed by physiological and metabolic stressors, which initiate transcriptional and translational signalling cascades to increase the abundance and/or function of proteins to improve physiological function. One important consideration is that training adaptations are reduced as training status increases, which is reflected at the molecular level as a blunting of the acute signalling response to exercise. This review examines blood-flow-restricted (BFR) exercise as a strategy for augmenting exercise-induced stressors and subsequent molecular signalling responses to enhance the physiological characteristics of the endurance athlete. Focus is placed on the processes of capillary growth and mitochondrial biogenesis. Recent evidence supports that BFR exercise presents an intensified training stimulus beyond that of performing the same exercise alone. We suggest that this has the potential to induce enhanced physiological adaptations, including increases in capillary supply and mitochondrial function, which can contribute to an improvement in performance of endurance exercise. There is, however, a lack of consensus regarding the potency of BFR training, which is invariably attributable to the different modes, intensities and durations of exercise and BFR methods. Further studies are needed to confirm its potential in the endurance-trained athlete.
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Affiliation(s)
- Richard A Ferguson
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK
| | - Emma A Mitchell
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK
| | - Conor W Taylor
- Ineos Grenadiers Cycling Team, Bollin House, Wilmslow, UK
| | - David J Bishop
- Institute for Health and Sport (iHeS), Victoria University, Melbourne, Victoria, Australia
| | - Danny Christiansen
- Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA
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29
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Azevedo Voltarelli V, Coronado M, Gonçalves Fernandes L, Cruz Campos J, Jannig PR, Batista Ferreira JC, Fajardo G, Chakur Brum P, Bernstein D. β 2-Adrenergic Signaling Modulates Mitochondrial Function and Morphology in Skeletal Muscle in Response to Aerobic Exercise. Cells 2021; 10:cells10010146. [PMID: 33450889 PMCID: PMC7828343 DOI: 10.3390/cells10010146] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 12/28/2020] [Accepted: 01/11/2021] [Indexed: 02/06/2023] Open
Abstract
The molecular mechanisms underlying skeletal muscle mitochondrial adaptations induced by aerobic exercise (AE) are not fully understood. We have previously shown that AE induces mitochondrial adaptations in cardiac muscle, mediated by sympathetic stimulation. Since direct sympathetic innervation of neuromuscular junctions influences skeletal muscle homeostasis, we tested the hypothesis that β2-adrenergic receptor (β2-AR)-mediated sympathetic activation induces mitochondrial adaptations to AE in skeletal muscle. Male FVB mice were subjected to a single bout of AE on a treadmill (80% Vmax, 60 min) under β2-AR blockade with ICI 118,551 (ICI) or vehicle, and parameters of mitochondrial function and morphology/dynamics were evaluated. An acute bout of AE significantly increased maximal mitochondrial respiration in tibialis anterior (TA) isolated fiber bundles, which was prevented by β2-AR blockade. This increased mitochondrial function after AE was accompanied by a change in mitochondrial morphology towards fusion, associated with increased Mfn1 protein expression and activity. β2-AR blockade fully prevented the increase in Mfn1 activity and reduced mitochondrial elongation. To determine the mechanisms involved in mitochondrial modulation by β2-AR activation in skeletal muscle during AE, we used C2C12 myotubes, treated with the non-selective β-AR agonist isoproterenol (ISO) in the presence of the specific β2-AR antagonist ICI or during protein kinase A (PKA) and Gαi protein blockade. Our in vitro data show that β-AR activation significantly increases mitochondrial respiration in myotubes, and this response was dependent on β2-AR activation through a Gαs-PKA signaling cascade. In conclusion, we provide evidence for AE-induced β2-AR activation as a major mechanism leading to alterations in mitochondria function and morphology/dynamics. β2-AR signaling is thus a key-signaling pathway that contributes to skeletal muscle plasticity in response to exercise.
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Affiliation(s)
- Vanessa Azevedo Voltarelli
- Department of Biodynamics of the Human Body Movement, School of Physical Education and Sport, University of São Paulo, São Paulo 05508-030, SP, Brazil; (V.A.V.); (L.G.F.); (P.R.J.)
| | - Michael Coronado
- Department of Pediatrics, School of Medicine, Stanford University, Palo Alto, CA 94304, USA; (M.C.); (G.F.)
| | - Larissa Gonçalves Fernandes
- Department of Biodynamics of the Human Body Movement, School of Physical Education and Sport, University of São Paulo, São Paulo 05508-030, SP, Brazil; (V.A.V.); (L.G.F.); (P.R.J.)
| | - Juliane Cruz Campos
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-030, SP, Brazil; (J.C.C.); (J.C.B.F.)
| | - Paulo Roberto Jannig
- Department of Biodynamics of the Human Body Movement, School of Physical Education and Sport, University of São Paulo, São Paulo 05508-030, SP, Brazil; (V.A.V.); (L.G.F.); (P.R.J.)
| | - Julio Cesar Batista Ferreira
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-030, SP, Brazil; (J.C.C.); (J.C.B.F.)
- Department of Chemical and Systems Biology, School of Medicine, Stanford University, Palo Alto, CA 94304, USA
| | - Giovanni Fajardo
- Department of Pediatrics, School of Medicine, Stanford University, Palo Alto, CA 94304, USA; (M.C.); (G.F.)
| | - Patricia Chakur Brum
- Department of Biodynamics of the Human Body Movement, School of Physical Education and Sport, University of São Paulo, São Paulo 05508-030, SP, Brazil; (V.A.V.); (L.G.F.); (P.R.J.)
- Correspondence: or (P.C.B.); (D.B.); Tel.: +55-11-30913136 (P.C.B.); Fax: +55-11-38135921 (P.C.B.)
| | - Daniel Bernstein
- Department of Pediatrics, School of Medicine, Stanford University, Palo Alto, CA 94304, USA; (M.C.); (G.F.)
- Correspondence: or (P.C.B.); (D.B.); Tel.: +55-11-30913136 (P.C.B.); Fax: +55-11-38135921 (P.C.B.)
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30
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Mesquita PH, Lamb DA, Parry HA, Moore JH, Smith MA, Vann CG, Osburn SC, Fox CD, Ruple BA, Huggins KW, Fruge AD, Young KC, Kavazis AN, Roberts MD. Acute and chronic effects of resistance training on skeletal muscle markers of mitochondrial remodeling in older adults. Physiol Rep 2020; 8:e14526. [PMID: 32748504 PMCID: PMC7399374 DOI: 10.14814/phy2.14526] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 07/07/2020] [Accepted: 07/10/2020] [Indexed: 02/06/2023] Open
Abstract
We investigated the acute and chronic effects of resistance training (RT) on skeletal muscle markers of mitochondrial content and remodeling in older, untrained adults. Sixteen participants (n = 6 males, n = 10 females; age = 59 ± 4 years) completed 10 weeks of full-body RT (2 day/week). Muscle biopsies from the vastus lateralis were obtained prior to RT (Pre), 24 hr following the first training session (Acute), and 72 hr following the last training session (Chronic). Protein levels of mitochondrial electron transport chain complexes I-V (+39 to +180%, p ≤ .020) and markers of mitochondrial fusion Mfn1 (+90%, p = .003), Mfn2 (+110%, p < .001), and Opa1 (+261%, p = .004) increased following chronic RT. Drp1 protein levels also increased (+134%, p = .038), while Fis1 protein levels did not significantly change (-5%, p = .584) following chronic RT. Interestingly, protein markers of mitochondrial biogenesis (i.e., PGC-1α, TFAM, and NRF1) or mitophagy (i.e., Pink1 and Parkin) were not significantly altered (p > .050) after 10 weeks of RT. In summary, chronic RT promoted increases in content of electron transport chain proteins (i.e., increased protein levels of all five OXPHOS complexes) and increase in the levels of proteins related to mitochondrial dynamics (i.e., increase in fusion protein markers) in skeletal muscle of older adults. These results suggest that chronic RT could be a useful strategy to increase mitochondrial protein content in older individuals.
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Affiliation(s)
| | - Donald A. Lamb
- Department of Nutrition, Dietetics and Hospitality ManagementAuburn UniversityAuburnALUSA
| | | | | | | | | | | | | | | | - Kevin W. Huggins
- Department of Nutrition, Dietetics and Hospitality ManagementAuburn UniversityAuburnALUSA
| | - Andrew D. Fruge
- Department of Nutrition, Dietetics and Hospitality ManagementAuburn UniversityAuburnALUSA
| | - Kaelin C. Young
- School of KinesiologyAuburn UniversityAuburnALUSA
- Department of Cell Biology and PhysiologyEdward Via College of Osteopathic MedicineAuburnALUSA
| | | | - Michael D. Roberts
- School of KinesiologyAuburn UniversityAuburnALUSA
- Department of Cell Biology and PhysiologyEdward Via College of Osteopathic MedicineAuburnALUSA
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Ghanemi A, Melouane A, Yoshioka M, St-Amand J. Exercise and High-Fat Diet in Obesity: Functional Genomics Perspectives of Two Energy Homeostasis Pillars. Genes (Basel) 2020; 11:genes11080875. [PMID: 32752100 PMCID: PMC7463441 DOI: 10.3390/genes11080875] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 07/24/2020] [Accepted: 07/28/2020] [Indexed: 12/15/2022] Open
Abstract
The heavy impact of obesity on both the population general health and the economy makes clarifying the underlying mechanisms, identifying pharmacological targets, and developing efficient therapies for obesity of high importance. The main struggle facing obesity research is that the underlying mechanistic pathways are yet to be fully revealed. This limits both our understanding of pathogenesis and therapeutic progress toward treating the obesity epidemic. The current anti-obesity approaches are mainly a controlled diet and exercise which could have limitations. For instance, the “classical” anti-obesity approach of exercise might not be practical for patients suffering from disabilities that prevent them from routine exercise. Therefore, therapeutic alternatives are urgently required. Within this context, pharmacological agents could be relatively efficient in association to an adequate diet that remains the most efficient approach in such situation. Herein, we put a spotlight on potential therapeutic targets for obesity identified following differential genes expression-based studies aiming to find genes that are differentially expressed under diverse conditions depending on physical activity and diet (mainly high-fat), two key factors influencing obesity development and prognosis. Such functional genomics approaches contribute to elucidate the molecular mechanisms that both control obesity development and switch the genetic, biochemical, and metabolic pathways toward a specific energy balance phenotype. It is important to clarify that by “gene-related pathways”, we refer to genes, the corresponding proteins and their potential receptors, the enzymes and molecules within both the cells in the intercellular space, that are related to the activation, the regulation, or the inactivation of the gene or its corresponding protein or pathways. We believe that this emerging area of functional genomics-related exploration will not only lead to novel mechanisms but also new applications and implications along with a new generation of treatments for obesity and the related metabolic disorders especially with the modern advances in pharmacological drug targeting and functional genomics techniques.
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Affiliation(s)
- Abdelaziz Ghanemi
- Department of Molecular Medicine, Faculty of Medicine, Laval University, Québec, QC G1V 0A6, Canada; (A.G.); (A.M.)
- Functional Genomics Laboratory, Endocrinology and Nephrology Axis, CHU de Québec-Université Laval Research Center, Québec, QC G1V 4G2, Canada;
| | - Aicha Melouane
- Department of Molecular Medicine, Faculty of Medicine, Laval University, Québec, QC G1V 0A6, Canada; (A.G.); (A.M.)
- Functional Genomics Laboratory, Endocrinology and Nephrology Axis, CHU de Québec-Université Laval Research Center, Québec, QC G1V 4G2, Canada;
| | - Mayumi Yoshioka
- Functional Genomics Laboratory, Endocrinology and Nephrology Axis, CHU de Québec-Université Laval Research Center, Québec, QC G1V 4G2, Canada;
| | - Jonny St-Amand
- Department of Molecular Medicine, Faculty of Medicine, Laval University, Québec, QC G1V 0A6, Canada; (A.G.); (A.M.)
- Functional Genomics Laboratory, Endocrinology and Nephrology Axis, CHU de Québec-Université Laval Research Center, Québec, QC G1V 4G2, Canada;
- Correspondence: ; Tel.: +1-418-654-2296; Fax: +1-418-654-2761
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Association between muscle aerobic capacity and whole-body peak oxygen uptake. Eur J Appl Physiol 2020; 120:2029-2036. [PMID: 32596752 DOI: 10.1007/s00421-020-04402-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2019] [Accepted: 05/19/2020] [Indexed: 10/24/2022]
Abstract
PURPOSE Decline in skeletal muscle mitochondrial oxidative capacity (MOC) is associated with reduced aerobic capacity and increased risk of cardiovascular and metabolic disease. Measuring skeletal muscle MOC may be an alternative method to assess aerobic capacity, especially for individuals unable to perform a whole-body maximum oxygen uptake protocol. In this study, linear regression analysis in two leg muscles was performed to determine whether MOC values could be used to predict whole-body peak oxygen uptake. METHODS MOC was measured with near infrared spectroscopy (NIRS) in the medial gastrocnemius (MG) and vastus lateralis (VL) muscles of 26 participants (age, 27.1 ± 5.8 years old). Whole-body peak oxygen uptake (VO2 peak) was determined by indirect calorimetry during a continuous ramp protocol on a cycle ergometer. RESULTS VO2 peak values were significantly correlated with the muscle recovery rate constant (k) of the MG (kMG, r = 0.59; p < 0.01) and VL (kVL, r = 0.63; p < 0.01) muscles. Summing recovery rate constants of both muscles together (kMG + kVL) improved the strength of the correlation with VO2 peak (r = 0.78; p < 0.0001) and could explain a majority of the variance (R2 = 0.61) between the two measurements. CONCLUSION Data suggest that NIRS can provide reliable MOC measurements on two leg muscles that correlate well with whole-body peak oxygen uptake.
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Kwon I. Protective effects of endurance exercise on skeletal muscle remodeling against doxorubicin-induced myotoxicity in mice. Phys Act Nutr 2020; 24:11-21. [PMID: 32698257 PMCID: PMC7451836 DOI: 10.20463/pan.2020.0010] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/19/2020] [Accepted: 06/22/2020] [Indexed: 12/14/2022] Open
Abstract
PURPOSE Doxorubicin (DOX) is a potent anti-cancer drug that appears to have severe myotoxicity due to accumulation. The skeletal muscle has a regeneration capacity through satellite cell activation when exposed to extracellular stimulus or damage. Endurance exercise (EXE) is a therapeutic strategy that improves pathological features and contributes to muscle homeostasis. Thus, this study investigated the effect of EXE training in mitigating chronic DOX-induced myotoxicity. METHODS Male C57BL/6J mice were housed and allowed to acclimatize with free access to food and water. All the mice were randomly divided into four groups: sedentary control (CON, n=9), exercise training (EXE, n=9), doxorubicin treatment (DOX, n=9), doxorubicin treatment and exercise training (DOX+EXE, n=9) groups. The animals were intraperitoneally injected with 5 mg/kg/week of DOX treatment for 4 weeks, and EXE training was initiated for treadmill adaptation for 1 week and then performed for 4 weeks. Both sides of the soleus (SOL) muscle tissues were dissected and weighed after 24 hours of the last training sessions. RESULTS DOX chemotherapy induced an abnormal myofiber's phenotype and transition of myosin heavy chain (MHC) isoforms. The paired box 7 (PAX7) and myoblast determination protein 1 (MYOD) protein levels were triggered by DOX, while no alterations were shown for the myogenin (MYOG). DOX remarkably impaired the a-actinin (ACTN) protein, but the EXE training seems to repair it. DOX-induced myotoxicity stimulated the expression of the forkhead box O3 (FOXO3a) protein, which was accurately controlled and adjusted by the EXE training. However, the FOXO3a-mediated downstream markers were not associated with DOX and EXE. CONCLUSION EXE postconditioning provides protective effects against chronic DOX-induced myotoxicity, and should be recommended to alleviate cancer chemotherapy-induced late-onset myotoxicity.
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Affiliation(s)
- Insu Kwon
- Research Institute of Sports Science and Industry, Hanyang University, SeoulRepublic of Korea
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The Role of Nutri(epi)genomics in Achieving the Body's Full Potential in Physical Activity. Antioxidants (Basel) 2020; 9:antiox9060498. [PMID: 32517297 PMCID: PMC7346155 DOI: 10.3390/antiox9060498] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Accepted: 06/05/2020] [Indexed: 12/12/2022] Open
Abstract
Physical activity represents a powerful tool to achieve optimal health. The overall activation of several molecular pathways is associated with many beneficial effects, mainly converging towards a reduced systemic inflammation. Not surprisingly, regular activity can contribute to lowering the “epigenetic age”, acting as a modulator of risk toward several diseases and enhancing longevity. Behind this, there are complex molecular mechanisms induced by exercise, which modulate gene expression, also through epigenetic modifications. The exercise-induced epigenetic imprint can be transient or permanent and contributes to the muscle memory, which allows the skeletal muscle adaptation to environmental stimuli previously encountered. Nutrition, through key macro- and micronutrients with antioxidant properties, can play an important role in supporting skeletal muscle trophism and those molecular pathways triggering the beneficial effects of physical activity. Nutrients and antioxidant food components, reversibly altering the epigenetic imprint, have a big impact on the phenotype. This assigns a role of primary importance to nutri(epi)genomics, not only in optimizing physical performance, but also in promoting long term health. The crosstalk between physical activity and nutrition represents a major environmental pressure able to shape human genotypes and phenotypes, thus, choosing the right combination of lifestyle factors ensures health and longevity.
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Tobiansky DJ, Miles MC, Goller F, Fuxjager MJ. Androgenic modulation of extraordinary muscle speed creates a performance trade-off with endurance. J Exp Biol 2020; 223:jeb222984. [PMID: 32291320 DOI: 10.1242/jeb.222984] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 04/04/2020] [Indexed: 12/30/2022]
Abstract
Performance trade-offs can dramatically alter an organism's evolutionary trajectory by making certain phenotypic outcomes unattainable. Understanding how these trade-offs arise from an animal's design is therefore an important goal of biology. To explore this topic, we studied how androgenic hormones, which regulate skeletal muscle function, influence performance trade-offs relevant to different components of complex reproductive behaviour. We conducted this work in golden-collared manakins (Manacus vitellinus), a neotropical bird in which males court females by rapidly snapping their wings together above their back. Androgens help mediate this behavior by radically increasing the twitch speed of a dorsal wing muscle (scapulohumeralis caudalis, SH), which actuates the bird's wing-snap. Through hormone manipulations and in situ muscle recordings, we tested how these positive effects on SH speed influence trade-offs with endurance. Indeed, this latter trait impacts the display by shaping signal length. We found that androgen-dependent increases in SH speed incur a cost to endurance, particularly when this muscle performs at its functional limits. Moreover, when behavioural data were overlaid on our muscle recordings, displaying animals appeared to balance display speed with fatigue-induced muscle fusion (physiological tetanus) to generate the fastest possible signal while maintaining an appropriate signal duration. Our results point to androgen action as a functional trigger of trade-offs in sexual performance - these hormones enhance one element of a courtship display, but in doing so, impede another.
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Affiliation(s)
- Daniel J Tobiansky
- Department of Ecology and Evolutionary Biology, Brown University, Providence, RI 02912, USA
| | - Meredith C Miles
- Department of Ecology and Evolutionary Biology, Brown University, Providence, RI 02912, USA
| | - Franz Goller
- Department of Biology, The University of Utah, Salt Lake City, UT 84112, USA
- Institute for Zoophysiology, University of Münster, 48149 Münster, Germany
| | - Matthew J Fuxjager
- Department of Ecology and Evolutionary Biology, Brown University, Providence, RI 02912, USA
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Boulghobra D, Coste F, Geny B, Reboul C. Exercise training protects the heart against ischemia-reperfusion injury: A central role for mitochondria? Free Radic Biol Med 2020; 152:395-410. [PMID: 32294509 DOI: 10.1016/j.freeradbiomed.2020.04.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 04/01/2020] [Accepted: 04/07/2020] [Indexed: 12/11/2022]
Abstract
Ischemic heart disease is one of the main causes of morbidity and mortality worldwide. Physical exercise is an effective lifestyle intervention to reduce the risk factors for cardiovascular disease and also to improve cardiac function and survival in patients with ischemic heart disease. Among the strategies that contribute to reduce heart damages during ischemia and reperfusion, regular physical exercise is efficient both in rodent experimental models and in humans. However, the cellular and molecular mechanisms of the cardioprotective effects of exercise remain unclear. During ischemia and reperfusion, mitochondria are crucial players in cell death, but also in cell survival. Although exercise training can influence mitochondrial function, the consequences on heart sensitivity to ischemic insults remain elusive. In this review, we describe the effects of physical activity on cardiac mitochondria and their potential key role in exercise-induced cardioprotection against ischemia-reperfusion damage. Based on recent scientific data, we discuss the role of different pathways that might help to explain why mitochondria are a key target of exercise-induced cardioprotection.
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Affiliation(s)
| | - Florence Coste
- LAPEC EA4278, Avignon Université, F-84000, Avignon, France
| | - Bernard Geny
- EA3072, «Mitochondrie, Stress Oxydant, et Protection Musculaire», Université de Strasbourg, 67000, Strasbourg, France
| | - Cyril Reboul
- LAPEC EA4278, Avignon Université, F-84000, Avignon, France.
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Viruega H, Gaillard I, Briatte L, Gaviria M. Inter-Day Reliability and Changes of Surface Electromyography on Two Postural Muscles Throughout 12 Weeks of Hippotherapy on Patients with Cerebral Palsy: A Pilot Study. Brain Sci 2020; 10:brainsci10050281. [PMID: 32384678 PMCID: PMC7288184 DOI: 10.3390/brainsci10050281] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 04/22/2020] [Accepted: 04/30/2020] [Indexed: 11/16/2022] Open
Abstract
Cerebral palsy (CP) is an umbrella term covering a group of permanent developmental disorders of movement and posture characterized by highly variable clinical features. The aim of this study was to assess the short-term and mid-term effects of neurorehabilitation via hippotherapy on the contractile properties of two key postural muscles during functional sitting in such patients. Thirty-minute hippotherapy sessions were conducted biweekly for 12 weeks in 18 patients (18.1 ± 5.7 years old). Surface electromyography (EMG) was implemented bilaterally in rectus abdominis and adductor magnus. We quantitatively analyzed the amplitude of EMG signals in the time domain and its spectral characteristics in the frequency domain. EMGs were recorded at the beginning and end of each session on day one and at week six and week twelve. Statistical analysis revealed a substantial inter-day reliability of the EMG signals for both muscles, validating the methodological approach. To a lesser extent, while beyond the scope of the current study, quantitative changes suggested a more selective recruitment/contractile properties’ shift of the examined muscles. Exploring postural control during functional activities would contribute to understanding the relationship between structural impairment, activity performance and patient capabilities, allowing the design of neurorehabilitation programs aimed at improving postural and functional skills according to each individual’s needs. The present study provides basic quantitative data supporting the body of scientific evidence making hippotherapy an approach of choice for CP neurorehabilitation.
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Scaricamazza S, Salvatori I, Giacovazzo G, Loeffler JP, Renè F, Rosina M, Quessada C, Proietti D, Heil C, Rossi S, Battistini S, Giannini F, Volpi N, Steyn FJ, Ngo ST, Ferraro E, Madaro L, Coccurello R, Valle C, Ferri A. Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1 G93A Mice Predates Disease Onset and Is A Promising Therapeutic Target. iScience 2020; 23:101087. [PMID: 32371370 PMCID: PMC7200935 DOI: 10.1016/j.isci.2020.101087] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 03/13/2020] [Accepted: 04/15/2020] [Indexed: 12/12/2022] Open
Abstract
Patients with ALS show, in addition to the loss of motor neurons in the spinal cord, brainstem, and cerebral cortex, an abnormal depletion of energy stores alongside hypermetabolism. In this study, we show that bioenergetic defects and muscle remodeling occur in skeletal muscle of the SOD1G93A mouse model of ALS mice prior to disease onset and before the activation of muscle denervation markers, respectively. These changes in muscle physiology were followed by an increase in energy expenditure unrelated to physical activity. Finally, chronic treatment of SOD1G93A mice with Ranolazine, an FDA-approved inhibitor of fatty acid β-oxidation, led to a decrease in energy expenditure in symptomatic SOD1G93A mice, and this occurred in parallel with a robust, albeit temporary, recovery of the pathological phenotype.
Metabolic switch use occurs early in the skeletal muscle of SOD1G93A mice Mitochondrial impairment precedes locomotor deficits and evokes catabolic pathways Sarcolipin upregulation in presymptomatic SOD1G93A mice precedes hypermetabolism Pharmacological modulation of hypermetabolism improves locomotor performance
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Affiliation(s)
- Silvia Scaricamazza
- University of Rome Tor Vergata, Department of Biology, Rome, Italy; IRCCS Fondazione Santa Lucia, Rome, Italy
| | | | | | - Jean Philippe Loeffler
- Université de Strasbourg, UMR_S 1118, Strasbourg, France; INSERM, U1118, Central and Peripheral Mechanisms of Neurodegeneration, Strasbourg, France
| | - Frederique Renè
- Université de Strasbourg, UMR_S 1118, Strasbourg, France; INSERM, U1118, Central and Peripheral Mechanisms of Neurodegeneration, Strasbourg, France
| | - Marco Rosina
- University of Rome Tor Vergata, Department of Biology, Rome, Italy
| | - Cyril Quessada
- Université de Strasbourg, UMR_S 1118, Strasbourg, France; INSERM, U1118, Central and Peripheral Mechanisms of Neurodegeneration, Strasbourg, France
| | | | | | - Simona Rossi
- University of Rome Tor Vergata, Department of Biology, Rome, Italy; National Research Council, Institute of Translational Pharmacology (IFT), Rome, Italy
| | - Stefania Battistini
- University of Siena, Department of Medical, Surgical and Neurological Science, Siena, Italy
| | - Fabio Giannini
- University of Siena, Department of Medical, Surgical and Neurological Science, Siena, Italy
| | - Nila Volpi
- University of Siena, Department of Medical, Surgical and Neurological Science, Siena, Italy
| | - Frederik J Steyn
- School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia; Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia
| | - Shyuan T Ngo
- Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia; Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia
| | | | - Luca Madaro
- IRCCS Fondazione Santa Lucia, Rome, Italy; DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy
| | - Roberto Coccurello
- IRCCS Fondazione Santa Lucia, Rome, Italy; National Research Council, Institute for Complex System (ISC), Rome, Italy
| | - Cristiana Valle
- IRCCS Fondazione Santa Lucia, Rome, Italy; National Research Council, Institute of Translational Pharmacology (IFT), Rome, Italy.
| | - Alberto Ferri
- IRCCS Fondazione Santa Lucia, Rome, Italy; National Research Council, Institute of Translational Pharmacology (IFT), Rome, Italy.
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Acute hypertrophic but not maximal strength loading transiently enhances the kynurenine pathway towards kynurenic acid. Eur J Appl Physiol 2020; 120:1429-1436. [PMID: 32306154 PMCID: PMC7237519 DOI: 10.1007/s00421-020-04375-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Accepted: 04/09/2020] [Indexed: 11/24/2022]
Abstract
Purpose Due to distinct immuno- and neuro-modulatory properties, growing research interest focuses on exercise-induced alterations of the kynurenine (KYN) pathway in healthy and clinical populations. To date, knowledge about the impact of different acute strength exercise modalities on the KYN pathway is scarce. Therefore, we investigated the acute effects of hypertrophic (HYP) compared to maximal (MAX) strength loadings on the KYN pathway regulation. Methods Blood samples of twelve healthy males (mean age and weight: 23.5 ± 3.2 years; 77.5 ± 7.5 kg) were collected before (T0), immediately after (T1), and 1 h after completion (T2) of HYP (5 sets with 10 repetitions at 80% of 1RM) and MAX (15 sets with 1RM) loadings performed in a randomized cross-over design. Serum concentrations of tryptophan (TRP), KYN, kynurenic acid (KA), and quinolinic acid (QA) were assessed using high-performance liquid chromatography. Results The KA/KYN ratio increased from T0 to T1 (p = 0.01) and decreased from T1 to T2 (p = 0.011) in HYP, while it was maintained within MAX. Compared to MAX, serum concentrations of KA were greater in HYP at T1 (p = 0.014). Moreover, the QA/KA ratio was significantly lower in HYP than in MAX at T1 (p = 0.002). Conclusion Acute HYP loading led to increases in the metabolic flux yielding KA, thereby possibly promoting immunosuppression and neuroprotection. Our findings emphasize the potential of acute HYP exercise as short-term modulator of KYN pathway downstream to KA in healthy males and need to be proven in other samples. Electronic supplementary material The online version of this article (10.1007/s00421-020-04375-9) contains supplementary material, which is available to authorized users.
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Granata C, Oliveira RSF, Little JP, Bishop DJ. Forty high-intensity interval training sessions blunt exercise-induced changes in the nuclear protein content of PGC-1α and p53 in human skeletal muscle. Am J Physiol Endocrinol Metab 2020; 318:E224-E236. [PMID: 31794264 PMCID: PMC7052577 DOI: 10.1152/ajpendo.00233.2019] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 12/02/2019] [Accepted: 12/03/2019] [Indexed: 12/11/2022]
Abstract
Exercise-induced increases in peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and p53 protein content in the nucleus mediate the initial phase of exercise-induced mitochondrial biogenesis. Here, we investigated whether exercise-induced increases in these and other markers of mitochondrial biogenesis were altered after 40 sessions of twice-daily high-volume, high-intensity interval training (HVT) in human skeletal muscle. Vastus lateralis muscle biopsies were collected from 10 healthy recreationally active participants before, immediately postexercise, and 3 h after a session of high-intensity interval exercise (HIIE) performed at the same absolute exercise intensity before and after HVT (pre-HVT and post-HVT, respectively). The protein content of common markers of exercise-induced mitochondrial biogenesis was assessed in nuclear- and cytosolic-enriched fractions by immunoblotting; mRNA contents of key transcription factors and mitochondrial genes were assessed by qPCR. Despite exercise-induced increases in PGC-1α, p53, and plant homeodomain finger-containing protein 20 (PHF20) protein content, the phosphorylation of p53 and acetyl-CoA carboxylase (p-p53 Ser15 and p-ACC Ser79, respectively), and PGC-1α mRNA Pre-HVT, no significant changes were observed post-HVT. Forty sessions of twice-daily high-intensity interval training blunted all of the measured exercise-induced molecular events associated with mitochondrial biogenesis that were observed pre-HVT. Future studies should determine whether this loss relates to the decrease in relative exercise intensity, habituation to the same exercise stimulus, or a combination of both.
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Affiliation(s)
- Cesare Granata
- Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Rodrigo S F Oliveira
- Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
| | - Jonathan P Little
- School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, British Columbia, Canada
| | - David J Bishop
- Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
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Hwang PS, Machek SB, Cardaci TD, Wilburn DT, Kim CS, Suezaki ES, Willoughby DS. Effects of Pyrroloquinoline Quinone (PQQ) Supplementation on Aerobic Exercise Performance and Indices of Mitochondrial Biogenesis in Untrained Men. J Am Coll Nutr 2019; 39:547-556. [PMID: 31860387 DOI: 10.1080/07315724.2019.1705203] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Objective: Pyrroloquinoline quinone (PQQ) is a novel supplement involved in processes such as mitochondrial biogenesis and cellular energy metabolism. Since endurance exercise and PQQ exhibit similar mechanisms for mitochondrial biogenesis, it is plausible that PQQ may have ergogenic value. Therefore, the purpose of this study was to examine the effects of a six-week endurance exercise training program on mitochondrial biogenesis and aerobic performance in non-endurance-trained males.Methods: Twenty-three males were randomized to consume 20 mg/day of PQQ or placebo (PLC). Both groups followed a supervised six-week endurance exercise training program. Body composition was assessed by dual-energy-x-ray-absorptiometry (DEXA). Aerobic exercise performance and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a biochemical marker for mitochondrial biogenesis, were assessed before and after the six-week endurance training/supplementation program.Results: There were no significant differences between groups in aerobic performance after endurance-training (p > 0.05). However, there were significant improvements in peak oxygen consumption (VO2peak) and total exercise test duration after endurance-training, irrespective of group (p < 0.05). The PQQ group had a significant increase in PGC-1α protein levels from baseline to post endurance training compared to PLC (p < 0.05). Furthermore, the PQQ group had higher PGC-1α protein levels after 6 weeks of endurance training compared to PLC (p < 0.05).Conclusions: Supplementation of PQQ does not appear to elicit any ergogenic effects regarding aerobic performance or body composition but appears to impact mitochondrial biogenesis by way of significant elevations in PGC-1α protein content.
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Affiliation(s)
- Paul S Hwang
- Department of Health, Human Performance, and Recreation, Exercise and Biochemical Nutrition Laboratory, Baylor University, Waco, Texas, USA
| | - Steven B Machek
- Department of Health, Human Performance, and Recreation, Exercise and Biochemical Nutrition Laboratory, Baylor University, Waco, Texas, USA
| | - Thomas D Cardaci
- Department of Health, Human Performance, and Recreation, Exercise and Biochemical Nutrition Laboratory, Baylor University, Waco, Texas, USA
| | - Dylan T Wilburn
- Department of Health, Human Performance, and Recreation, Exercise and Biochemical Nutrition Laboratory, Baylor University, Waco, Texas, USA
| | - Caelin S Kim
- Department of Health, Human Performance, and Recreation, Exercise and Biochemical Nutrition Laboratory, Baylor University, Waco, Texas, USA
| | - Emiliya S Suezaki
- Department of Health, Human Performance, and Recreation, Exercise and Biochemical Nutrition Laboratory, Baylor University, Waco, Texas, USA
| | - Darryn S Willoughby
- Department of Health, Human Performance, and Recreation, Exercise and Biochemical Nutrition Laboratory, Baylor University, Waco, Texas, USA
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Memme JM, Erlich AT, Phukan G, Hood DA. Exercise and mitochondrial health. J Physiol 2019; 599:803-817. [PMID: 31674658 DOI: 10.1113/jp278853] [Citation(s) in RCA: 156] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 10/28/2019] [Indexed: 12/12/2022] Open
Abstract
Mitochondrial health is an important mediator of cellular function across a range of tissues, and as a result contributes to whole-body vitality in health and disease. Our understanding of the regulation and function of these organelles is of great interest to scientists and clinicians across many disciplines within our healthcare system. Skeletal muscle is a useful model tissue for the study of mitochondrial adaptations because of its mass and contribution to whole body metabolism. The remarkable plasticity of mitochondria allows them to adjust their volume, structure and capacity under conditions such as exercise, which is useful or improving metabolic health in individuals with various diseases and/or advancing age. Mitochondria exist within muscle as a functional reticulum which is maintained by dynamic processes of biogenesis and fusion, and is balanced by opposing processes of fission and mitophagy. The sophisticated coordination of these events is incompletely understood, but is imperative for organelle function and essential for the maintenance of an interconnected organelle network that is finely tuned to the metabolic needs of the cell. Further elucidation of the mechanisms of mitochondrial turnover in muscle could offer potential therapeutic targets for the advancement of health and longevity among our ageing populations. As well, investigating exercise modalities that are both convenient and capable of inducing robust mitochondrial adaptations are useful in fostering more widespread global adherence. To this point, exercise remains the most potent behavioural therapeutic approach for the improvement of mitochondrial health, not only in muscle, but potentially also in other tissues.
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Affiliation(s)
- Jonathan M Memme
- Muscle Health Research Centre, York University, Toronto, Ontario, Canada, M3J 1P3.,School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada, M3J 1P3
| | - Avigail T Erlich
- Muscle Health Research Centre, York University, Toronto, Ontario, Canada, M3J 1P3.,School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada, M3J 1P3
| | - Geetika Phukan
- Muscle Health Research Centre, York University, Toronto, Ontario, Canada, M3J 1P3.,School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada, M3J 1P3
| | - David A Hood
- Muscle Health Research Centre, York University, Toronto, Ontario, Canada, M3J 1P3.,School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada, M3J 1P3
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Ng SY, Mikhail A, Ljubicic V. Mechanisms of exercise-induced survival motor neuron expression in the skeletal muscle of spinal muscular atrophy-like mice. J Physiol 2019; 597:4757-4778. [PMID: 31361024 PMCID: PMC6767691 DOI: 10.1113/jp278454] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 07/26/2019] [Indexed: 12/29/2022] Open
Abstract
Key points
Spinal muscular atrophy (SMA) is a health‐ and life‐limiting neuromuscular disorder caused by a deficiency in survival motor neuron (SMN) protein. While historically considered a motor neuron disease, current understanding of SMA emphasizes its systemic nature, which requires addressing affected peripheral tissues such as skeletal muscle in particular. Chronic physical activity is beneficial for SMA patients, but the cellular and molecular mechanisms of exercise biology are largely undefined in SMA. After a single bout of exercise, canonical responses such as skeletal muscle AMP‐activated protein kinase (AMPK), p38 mitogen‐activated protein kinase (p38) and peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) activation were preserved in SMA‐like Smn2B/− animals. Furthermore, molecules involved in SMN transcription were also altered following physical activity. Collectively, these changes were coincident with an increase in full‐length SMN transcription and corrective SMN pre‐mRNA splicing. This study advances understanding of the exercise biology of SMA and highlights the AMPK–p38–PGC‐1α axis as a potential regulator of SMN expression in muscle. Abstract Chronic physical activity is safe and effective in spinal muscular atrophy (SMA) patients, but the underlying cellular events that drive physiological adaptations are undefined. We examined the effects of a single bout of exercise on molecular mechanisms associated with adaptive remodelling in the skeletal muscle of Smn2B/− SMA‐like mice. Skeletal muscles were collected from healthy Smn2B/+ mice and Smn2B/− littermates at pre‐ (postnatal day (P) 9), early‐ (P13) and late‐ (P21) symptomatic stages to characterize SMA disease progression. Muscles were also collected from Smn2B/− animals exercised to fatigue on a motorized treadmill. Intracellular signalling and gene expression were examined using western blotting, confocal immunofluorescence microscopy, real‐time quantitative PCR and endpoint PCR assays. Basal skeletal muscle AMP‐activated protein kinase (AMPK) and p38 mitogen‐activated protein kinase (p38) expression and activity were not affected by SMA‐like conditions. Canonical exercise responses such as AMPK, p38 and peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) activation were observed following a bout of exercise in Smn2B/− animals. Furthermore, molecules involved in survival motor neuron (SMN) transcription, including protein kinase B (AKT) and extracellular signal‐regulated kinases (ERK)/ETS‐like gene 1 (ELK1), were altered following physical activity. Acute exercise was also able to mitigate aberrant proteolytic signalling in the skeletal muscle of Smn2B/− mice. Collectively, these changes were coincident with an exercise‐evoked increase in full‐length SMN mRNA expression. This study advances our understanding of the exercise biology of SMA and highlights the AMPK–p38–PGC‐1α axis as a potential regulator of SMN expression alongside AKT and ERK/ELK1 signalling.
Spinal muscular atrophy (SMA) is a health‐ and life‐limiting neuromuscular disorder caused by a deficiency in survival motor neuron (SMN) protein. While historically considered a motor neuron disease, current understanding of SMA emphasizes its systemic nature, which requires addressing affected peripheral tissues such as skeletal muscle in particular. Chronic physical activity is beneficial for SMA patients, but the cellular and molecular mechanisms of exercise biology are largely undefined in SMA. After a single bout of exercise, canonical responses such as skeletal muscle AMP‐activated protein kinase (AMPK), p38 mitogen‐activated protein kinase (p38) and peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) activation were preserved in SMA‐like Smn2B/− animals. Furthermore, molecules involved in SMN transcription were also altered following physical activity. Collectively, these changes were coincident with an increase in full‐length SMN transcription and corrective SMN pre‐mRNA splicing. This study advances understanding of the exercise biology of SMA and highlights the AMPK–p38–PGC‐1α axis as a potential regulator of SMN expression in muscle.
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Affiliation(s)
- Sean Y Ng
- Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada
| | - Andrew Mikhail
- Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada
| | - Vladimir Ljubicic
- Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada
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Willingham TB, Melbourn J, Moldavskiy M, McCully KK, Backus D. Effects of Treadmill Training on Muscle Oxidative Capacity and Endurance in People with Multiple Sclerosis with Significant Walking Limitations. Int J MS Care 2019; 21:166-172. [PMID: 31474809 DOI: 10.7224/1537-2073.2018-021] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Background Exercise can improve muscle function and mobility in people with multiple sclerosis (MS). However, the effects of exercise training on skeletal muscle oxidative capacity and endurance in people with MS remain unclear, and few studies have evaluated muscle plasticity in people with MS who have moderate-to-severe disability. The present study evaluated the effects of treadmill training on muscle oxidative capacity and muscle endurance and examined the relationship to walking function in people with MS who have moderate-to-severe disability. Methods Six adults (mean ± SD age, 50 ± 4.9 years) with MS (Expanded Disability Status Scale score, 6.0-6.5) performed treadmill training for 24 minutes approximately twice per week for approximately 8 weeks (16 sessions total) using an antigravity treadmill system. The following measures were taken before and after the intervention phase: muscle oxidative capacity in the medial gastrocnemius using near-infrared spectroscopy after 15 to 20 seconds of electrical stimulation; muscle endurance in the medial gastrocnemius using accelerometer-based mechanomyography during 9 minutes of twitch electrical stimulation in three stages (3 minutes per stage) of increasing frequency (2, 4, and 6 Hz); and walking function using the 2-Minute Walk Test. Results Mean ± SD muscle oxidative capacity increased from 0.64 ± 0.19 min-1 to 1.08 ± 0.52 min-1 (68.2%). Mean ± SD muscle endurance increased from 80.9% ± 15.2% to 91.5% ± 4.8% at 2 Hz, from 56.3% ± 20.1% to 76.6% ± 15.8% at 4 Hz, and from 29.2% ± 13.1% to 53.9% ± 19.4% at 6 Hz of stimulation in the gastrocnemius. There were no significant improvements in walking function. Conclusions Treadmill training can improve muscle oxidative capacity and endurance in people with MS who have moderate-to-severe levels of disability.
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N-acetyl-L-cysteine Prevents Lactate-Mediated PGC1-alpha Expression in C2C12 Myotubes. BIOLOGY 2019; 8:biology8020044. [PMID: 31185672 PMCID: PMC6627666 DOI: 10.3390/biology8020044] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 06/04/2019] [Accepted: 06/05/2019] [Indexed: 11/21/2022]
Abstract
Background: Exercise induces many physiological adaptations. Recently, it has been proposed that some of these adaptations are induced by exercise-mediated lactate production. In this study, we aimed to investigate in vitro the effect of lactate in cultured myotubes and whether antioxidants could inhibit the effect. Methods: Differentiated myotubes were cultured at different concentrations of L-lactate (0, 10, 30, 50 mM) in the absence or presence of an antioxidant, N-acetyl-L-cysteine (Nac). The temporal effect of lactate exposure in myotubes was also explored. Results: Two hours of exposure to 50 mM L-lactate and six hours of exposure to 30 or 50 mM L-lactate caused a significant increase in PGC1-alpha (peroxisome proliferator-activated receptor γ coactivator-1α) expression in the myotubes. This up-regulation was suppressed by 2 mM Nac. Intermittent and continuous lactate exposure caused similar PGC1-alpha up-regulation. These results suggest that the increase in PGC1-alpha expression is mediated by reactive oxygen species (ROS) production from lactate metabolism and that both continuous and intermittent exposure to L-lactate can cause the up-regulation.
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48
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Skeletal muscle excitation-metabolism coupling. Arch Biochem Biophys 2019; 664:89-94. [DOI: 10.1016/j.abb.2019.01.037] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 01/30/2019] [Accepted: 01/31/2019] [Indexed: 01/17/2023]
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Manta A, Stouth DW, Xhuti D, Chi L, Rebalka IA, Kalmar JM, Hawke TJ, Ljubicic V. Chronic exercise mitigates disease mechanisms and improves muscle function in myotonic dystrophy type 1 mice. J Physiol 2019; 597:1361-1381. [PMID: 30628727 DOI: 10.1113/jp277123] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2018] [Accepted: 01/04/2019] [Indexed: 12/14/2022] Open
Abstract
KEY POINTS Myotonic dystrophy type 1 (DM1), the second most common muscular dystrophy and most prevalent adult form of muscular dystrophy, is characterized by muscle weakness, wasting and myotonia. A microsatellite repeat expansion mutation results in RNA toxicity and dysregulation of mRNA processing, which are the primary downstream causes of the disorder. Recent studies with DM1 participants demonstrate that exercise is safe, enjoyable and elicits benefits in muscle strength and function; however, the molecular mechanisms of exercise adaptation in DM1 are undefined. Our results demonstrate that 7 weeks of volitional running wheel exercise in a pre-clinical DM1 mouse model resulted in significantly improved motor performance, muscle strength and endurance, as well as reduced myotonia. At the cellular level, chronic physical activity attenuated RNA toxicity, liberated Muscleblind-like 1 protein from myonuclear foci and improved mRNA alternative splicing. ABSTRACT Myotonic dystrophy type 1 (DM1) is a trinucleotide repeat expansion neuromuscular disorder that is most prominently characterized by skeletal muscle weakness, wasting and myotonia. Chronic physical activity is safe and satisfying, and can elicit functional benefits such as improved strength and endurance in DM1 patients, but the underlying cellular basis of exercise adaptation is undefined. Our purpose was to examine the mechanisms of exercise biology in DM1. Healthy, sedentary wild-type (SED-WT) mice, as well as sedentary human skeletal actin-long repeat animals, a murine model of DM1 myopathy (SED-DM1), and DM1 mice with volitional access to a running wheel for 7 weeks (EX-DM1), were utilized. Chronic exercise augmented strength and endurance in vivo and in situ in DM1 mice. These alterations coincided with normalized measures of myopathy, as well as increased mitochondrial content. Electromyography revealed a 70-85% decrease in the duration of myotonic discharges in muscles from EX-DM1 compared to SED-DM1 animals. The exercise-induced enhancements in muscle function corresponded at the molecular level with mitigated spliceopathy, specifically the processing of bridging integrator 1 and muscle-specific chloride channel (CLC-1) transcripts. CLC-1 protein content and sarcolemmal expression were lower in SED-DM1 versus SED-WT animals, but they were similar between SED-WT and EX-DM1 groups. Chronic exercise also attenuated RNA toxicity, as indicated by reduced (CUG)n foci-positive myonuclei and sequestered Muscleblind-like 1 (MBNL1). Our data indicate that chronic exercise-induced physiological improvements in DM1 occur in concert with mitigated primary downstream disease mechanisms, including RNA toxicity, MBNL1 loss-of-function, and alternative mRNA splicing.
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Affiliation(s)
- Alexander Manta
- Department of Kinesiology, McMaster University, Hamilton, ON, Canada, L8S 4K1
| | - Derek W Stouth
- Department of Kinesiology, McMaster University, Hamilton, ON, Canada, L8S 4K1
| | - Donald Xhuti
- Department of Kinesiology, McMaster University, Hamilton, ON, Canada, L8S 4K1
| | - Leon Chi
- Department of Kinesiology, McMaster University, Hamilton, ON, Canada, L8S 4K1
| | - Irena A Rebalka
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada, L8S 4K1
| | - Jayne M Kalmar
- Department of Kinesiology & Physical Education, Wilfred Laurier University, Waterloo, ON, Canada, N2L 3C5
| | - Thomas J Hawke
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada, L8S 4K1
| | - Vladimir Ljubicic
- Department of Kinesiology, McMaster University, Hamilton, ON, Canada, L8S 4K1
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Changes in Redox Signaling in the Skeletal Muscle with Aging. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:4617801. [PMID: 30800208 PMCID: PMC6360032 DOI: 10.1155/2019/4617801] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 11/05/2018] [Accepted: 11/22/2018] [Indexed: 01/01/2023]
Abstract
Reduction in muscle strength with aging is due to both loss of muscle mass (quantity) and intrinsic force production (quality). Along with decreased functional capacity of the muscle, age-related muscle loss is associated with corresponding comorbidities and healthcare costs. Mitochondrial dysfunction and increased oxidative stress are the central driving forces for age-related skeletal muscle abnormalities. The increased oxidative stress in the aged muscle can lead to altered excitation-contraction coupling and calcium homeostasis. Furthermore, apoptosis-mediated fiber loss, atrophy of the remaining fibers, dysfunction of the satellite cells (muscle stem cells), and concomitant impaired muscle regeneration are also the consequences of increased oxidative stress, leading to a decrease in muscle mass, strength, and function of the aged muscle. Here we summarize the possible effects of oxidative stress in the aged muscle and the benefits of physical activity and antioxidant therapy.
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