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Davie A, Beavers R, Denham J. The application of the pyramidal training model for conditioning thoroughbred horses. J Equine Vet Sci 2025; 149:105567. [PMID: 40216095 DOI: 10.1016/j.jevs.2025.105567] [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: 10/12/2024] [Revised: 04/08/2025] [Accepted: 04/08/2025] [Indexed: 04/17/2025]
Abstract
The purpose of this review was to analyze the scientific background and practical application of a very successful human training methodology, the pyramidal training model, to the Thoroughbred racehorse. Despite years of research and accumulated knowledge on human training methods to enhance endurance performance, Thoroughbred training programs have lacked significant change. This review introduces the pyramidal training model, explains the science that underpins this training concept and outlines one approach to translate this science into the equine field. It also discusses the importance of training load and provides insight into the monitoring of the load and psychophysiological stress level of the horse during training. The use of heart rate and blood lactate responses to exercise is encouraged to guide exercise training sessions. These responses are the best indices of internal load, and the most accurate measure of effort in horses. Applying this information can help provide the desired training stimulus and overall training workload to maximize endurance performance.
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Affiliation(s)
- Allan Davie
- Australian Equine Racing and Research Centre, Ballina, New South Wales, 2478, Australia
| | - Rosalind Beavers
- Faculty of Health Sciences, Southern Cross University, East Lismore, New South Wales, 2480, Australia
| | - Joshua Denham
- School of Health and Medical Sciences, University of Southern Queensland, Ipswich,4305, Queensland, Australia; Centre for Health Research, Toowoomba, Queensland, 4350, Australia.
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Pan C, Yang Y, Zhao Z, Hu J. Combined effects of natural products and exercise on apoptosis pathways in obesity-related skeletal muscle dysfunction. Apoptosis 2025; 30:537-552. [PMID: 39833631 DOI: 10.1007/s10495-024-02069-7] [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] [Accepted: 12/23/2024] [Indexed: 01/22/2025]
Abstract
Obesity and related metabolic disorders are closely linked to increased apoptosis in skeletal muscle, leading to muscle degeneration, insulin resistance, and the progression of diseases such as type 2 diabetes and sarcopenia. This review explores the combined effects of natural products, including resveratrol, curcumin, and quercetin, and physical exercise on modulating apoptosis pathways in skeletal muscle. Both natural products and regular physical activity independently reduce oxidative stress and improve mitochondrial function, thereby regulating the balance between pro-apoptotic and anti-apoptotic signals. When combined, these interventions amplify their protective effects on muscle health, promoting mitochondrial biogenesis, reducing apoptosis, and enhancing muscle regeneration. This review also discusses the molecular mechanisms by which these strategies influence apoptosis, with a focus on the Bcl-2 pathway, and explores the clinical implications for the prevention and treatment of obesity-related diseases. The synergistic benefits of combining exercise with natural product supplementation offer a promising therapeutic approach for managing metabolic disorders, preserving muscle function, and improving overall metabolic health.
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Affiliation(s)
- Chun Pan
- School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, Guizhou, China
| | - Yiying Yang
- School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, Guizhou, China
| | - Zailin Zhao
- School of Law, Guizhou University, Guiyang, 550025, Guizhou, China
| | - Jingye Hu
- School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, Guizhou, China.
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Khoramipour K, Soltany A, Khosravi P, Rezaei MH, Madadizadeh E, García-Chico C, Maroto-Izquierdo S, Khoramipour K. High intensity interval training as a therapy: Mitophagy restoration in breast cancer. Arch Biochem Biophys 2024; 762:110213. [PMID: 39515549 DOI: 10.1016/j.abb.2024.110213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Revised: 11/05/2024] [Accepted: 11/06/2024] [Indexed: 11/16/2024]
Abstract
Recent studies have highlighted the role of mitophagy in tumorigenesis. This study aimed to investigate the effects of high-intensity interval training (HIIT) on mitophagy in tumor tissues of mice with breast cancer. Twenty-eight female BALB/c mice were randomly assigned to four groups: Healthy Control (CO), Cancer (CA), Exercise (EX), and Cancer + Exercise (CA + EX). Mammary tumors were induced in the CA and CA + EX groups via 4T1 cell injections. Upon confirmation of tumor formation, the EX and CA + EX groups underwent 8 weeks (40 sessions) of HIIT, comprising 4-10 intervals of running at 80-100 % of maximum speed. The expression levels of mitophagy-related proteins, including parkin, PTEN-induced putative kinase 1 (PINK1), NIP3-like protein X (NIX), BCL2 interacting protein-3 (BINP3), microtubule-associated protein light chain 3-I (LC3-I), microtubule-associated protein light chain 3-II (LC3-II), AMP-activated protein kinase (AMPK), Unc-51 like autophagy activating kinase-1 (ULK1), and sirtuin-1 (SIRT1), were measured in breast and tumor tissues. Tumor volume relative to body weight was assessed weekly during the eight-week HIIT intervention. Protein expression of parkin, PINK1, NIX, BINP3, LC3-II, LC3-I, AMPK, ULK1, and SIRT1 was reduced in the breast tissue of the CA group, while HIIT restored expression levels across all measured variables (P < 0.01). Additionally, tumor volume relative to body weight was significantly lower in the CA + EX group compared to the CA group from weeks 3-8 (P < 0.01). These findings suggest that breast cancer suppresses mitophagy, yet HIIT effectively reverses this suppression, potentially reducing tumor burden. HIIT may thus represent a promising therapeutic strategy for managing breast cancer.
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Affiliation(s)
- Kayvan Khoramipour
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), 47012, Valladolid, Spain.
| | - Afsaneh Soltany
- Department of Biology, Faculty of Science, University of Shiraz, Shiraz, Iran.
| | - Pouria Khosravi
- Department of Sports Physiology, Faculty of Physical Education and Sports Sciences, Shahid Rajaei Teacher Training University, Tehran, Iran.
| | - Maryam Hossein Rezaei
- Department of Exercise Physiology, Faculty of Physical Education, Shahid Bahonar University, Kerman, Iran.
| | - Elham Madadizadeh
- Department of Exercise Physiology, Faculty of Physical Education, Shahid Bahonar University, Kerman, Iran.
| | - Celia García-Chico
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), 47012, Valladolid, Spain.
| | - Sergio Maroto-Izquierdo
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), 47012, Valladolid, Spain.
| | - Karen Khoramipour
- Department of Sport Sines, Faculty of Humanities and Social Sciences, University of Kurdistan, Kurdistan, Iran.
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Berger N, Kugler B, Han D, Li M, Nguyen P, Anderson M, Zhang S, Cai C, Zou K. Voluntary Exercise Attenuates Tumor Growth in a Preclinical Model of Castration-Resistant Prostate Cancer. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.10.16.617081. [PMID: 39464116 PMCID: PMC11507860 DOI: 10.1101/2024.10.16.617081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/29/2024]
Abstract
Purpose To examine the effects of voluntary exercise training on tumor growth and explore the underlying intratumoral molecular pathways and processes responsible for the beneficial effects of VWR on tumor initiation and progression in a mouse model of Castration-Resistant Prostate Cancer (CRPC). Methods Male immunodeficient mice (SCID) were castrated and subcutaneously inoculated with human CWR-22RV1 cancer cells to construct CRPC xenograft model before randomly assigned to either voluntary wheel running (VWR) or sedentary (SED) group (n=6/group). After three weeks, tumor tissues were collected. Tumor size was measured and calculated. mRNA expression of markers of DNA replication, Androgen Receptor (AR) signaling, and mitochondrial dynamics was determined by RT-PCR. Protein expression of mitochondrial content and dynamics was determined by western blotting. Finally, RNA-sequencing analysis was performed in the tumor tissues. Results Voluntary wheel running resulted in smaller tumor volume at the initial stage and attenuated tumor progression throughout the time course (P < 0.05). The reduction of tumor volume in VWR group was coincided with lower mRNA expression of DNA replication markers ( MCM2 , MCM6 , and MCM7 ), AR signaling ( ELOVL5 and FKBP5 ) and regulatory proteins of mitochondrial fission (Drp1 and Fis1) and fusion (MFN1 and OPA1) when compared to the SED group (P<0.05). More importantly, RNA sequencing data further revealed that pathways related to pathways related to angiogenesis, extracellular matrix formation and endothelial cell proliferation were downregulated. Conclusions Three weeks of VWR was effective in delaying tumor initiation and progression, which coincided with reduced transcription of DNA replication, AR signaling targets and mitochondrial dynamics. We further identified reduced molecular pathways/processes related to angiogenesis that may be responsible for the delayed tumor initiation and progression by VWR.
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Xia Q, Li P, Casas-Martinez JC, Miranda-Vizuete A, McDermott E, Dockery P, Goljanek-Whysall K, McDonagh B. Peroxiredoxin 2 regulates DAF-16/FOXO mediated mitochondrial remodelling in response to exercise that is disrupted in ageing. Mol Metab 2024; 88:102003. [PMID: 39117041 PMCID: PMC11388264 DOI: 10.1016/j.molmet.2024.102003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 07/25/2024] [Accepted: 08/01/2024] [Indexed: 08/10/2024] Open
Abstract
OBJECTIVES A decline in mitochondrial function and increased susceptibility to oxidative stress is a hallmark of ageing. Exercise endogenously generates reactive oxygen species (ROS) in skeletal muscle and promotes mitochondrial remodelling resulting in improved mitochondrial function. It is unclear how exercise induced redox signalling results in alterations in mitochondrial dynamics and morphology. METHODS In this study, a Caenorhabditis elegans model of exercise and ageing was used to determine the mechanistic role of Peroxiredoxin 2 (PRDX-2) in regulating mitochondrial morphology. Mitochondrial morphology was analysed using transgenic reporter strains and transmission electron microscopy, complimented with the analysis of the effects of ageing and exercise on physiological activity. RESULTS The redox state of PRDX-2 was altered with exercise and ageing, hyperoxidised peroxiredoxins were detected in old worms along with basally elevated intracellular ROS. Exercise generated intracellular ROS and rapid mitochondrial remodelling, which was disrupted with age. The exercise intervention promoted mitochondrial ER contact sites (MERCS) assembly and increased DAF-16/FOXO nuclear localisation. The prdx-2 mutant strain had a disrupted mitochondrial network as evidenced by increased mitochondrial fragmentation. In the prdx-2 mutant strain, exercise did not activate DAF-16/FOXO, mitophagy or increase MERCS assembly. The results demonstrate that exercise generated ROS increased DAF-16/FOXO transcription factor nuclear localisation required for activation of mitochondrial fusion events that were blunted with age. CONCLUSIONS The data demonstrate the critical role of PRDX-2 in orchestrating mitochondrial remodelling in response to a physiological stress by regulating redox dependent DAF-16/FOXO nuclear localisation.
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Affiliation(s)
- Qin Xia
- Discipline of Physiology, School of Medicine, Ireland; Apoptosis Research Centre, University of Galway, Ireland
| | - Penglin Li
- Discipline of Physiology, School of Medicine, Ireland; Apoptosis Research Centre, University of Galway, Ireland
| | - José C Casas-Martinez
- Discipline of Physiology, School of Medicine, Ireland; Apoptosis Research Centre, University of Galway, Ireland
| | - Antonio Miranda-Vizuete
- Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain
| | - Emma McDermott
- Centre for Microscopy and Imaging, Discipline of Anatomy, School of Medicine, University of Galway, Ireland
| | - Peter Dockery
- Centre for Microscopy and Imaging, Discipline of Anatomy, School of Medicine, University of Galway, Ireland
| | - Katarzyna Goljanek-Whysall
- Discipline of Physiology, School of Medicine, Ireland; Apoptosis Research Centre, University of Galway, Ireland; Institute of Lifecourse and Medical Sciences, University of Liverpool, UK
| | - Brian McDonagh
- Discipline of Physiology, School of Medicine, Ireland; Apoptosis Research Centre, University of Galway, Ireland.
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Martinez-Canton M, Galvan-Alvarez V, Gallego-Selles A, Gelabert-Rebato M, Garcia-Gonzalez E, Gonzalez-Henriquez JJ, Martin-Rincon M, Calbet JAL. Activation of macroautophagy and chaperone-mediated autophagy in human skeletal muscle by high-intensity exercise in normoxia and hypoxia and after recovery with or without post-exercise ischemia. Free Radic Biol Med 2024; 222:607-624. [PMID: 39009244 DOI: 10.1016/j.freeradbiomed.2024.07.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Revised: 06/25/2024] [Accepted: 07/11/2024] [Indexed: 07/17/2024]
Abstract
Autophagy is essential for the adaptive response to exercise and physiological skeletal muscle functionality. However, the mechanisms leading to the activation of macroautophagy and chaperone-mediated autophagy in human skeletal muscle in response to high-intensity exercise remain elusive. Our findings demonstrate that macroautophagy and chaperone-mediated autophagy are stimulated by high-intensity exercise in normoxia (PIO2: 143 mmHg) and severe acute hypoxia (PIO2: 73 mmHg) in healthy humans. High-intensity exercise induces macroautophagy initiation through AMPKα phosphorylation, which phosphorylates and activates ULK1. ULK1 phosphorylates BECN1 at Ser15, eliciting the dissociation of BECN1-BCL2 crucial for phagophore formation. Besides, high-intensity exercise elevates the LC3B-II:LC3B-I ratio, reduces total SQSTM1/p62 levels, and induces p-Ser349 SQSTM1/p62 phosphorylation, suggesting heightened autophagosome degradation. PHAF1/MYTHO, a novel macroautophagy biomarker, is highly upregulated in response to high-intensity exercise. The latter is accompanied by elevated LAMP2A expression, indicating chaperone-mediated autophagy activation regardless of post-exercise HSPA8/HSC70 downregulation. Despite increased glycolytic metabolism, severe acute hypoxia does not exacerbate the autophagy signaling response. Signaling changes revert within 1 min of recovery with free circulation, while the application of immediate post-exercise ischemia impedes recovery. Our study concludes that macroautophagy and chaperone-mediated autophagy pathways are strongly activated by high-intensity exercise, regardless of PO2, and that oxygenation is necessary to revert these signals to pre-exercise values. PHAF1/MYTHO emerges as a pivotal exercise-responsive autophagy marker positively associated with the LC3B-II:LC3B-I ratio.
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Affiliation(s)
- Miriam Martinez-Canton
- Department of Physical Education, University of Las Palmas de Gran Canaria, Campus Universitario de Tafira s/n, Las Palmas de Gran Canaria, 35017, Spain; Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Canary Islands, Spain
| | - Victor Galvan-Alvarez
- Department of Physical Education, University of Las Palmas de Gran Canaria, Campus Universitario de Tafira s/n, Las Palmas de Gran Canaria, 35017, Spain; Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Canary Islands, Spain
| | - Angel Gallego-Selles
- Department of Physical Education, University of Las Palmas de Gran Canaria, Campus Universitario de Tafira s/n, Las Palmas de Gran Canaria, 35017, Spain; Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Canary Islands, Spain
| | - Miriam Gelabert-Rebato
- Department of Physical Education, University of Las Palmas de Gran Canaria, Campus Universitario de Tafira s/n, Las Palmas de Gran Canaria, 35017, Spain; Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Canary Islands, Spain
| | - Eduardo Garcia-Gonzalez
- Department of Physical Education, University of Las Palmas de Gran Canaria, Campus Universitario de Tafira s/n, Las Palmas de Gran Canaria, 35017, Spain; Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Canary Islands, Spain
| | - Juan Jose Gonzalez-Henriquez
- Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Canary Islands, Spain; Department of Mathematics, University of Las Palmas de Gran Canaria, Campus Universitario de Tafira s/n, Las Palmas de Gran Canaria, 35017, Spain
| | - Marcos Martin-Rincon
- Department of Physical Education, University of Las Palmas de Gran Canaria, Campus Universitario de Tafira s/n, Las Palmas de Gran Canaria, 35017, Spain; Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Canary Islands, Spain
| | - Jose A L Calbet
- Department of Physical Education, University of Las Palmas de Gran Canaria, Campus Universitario de Tafira s/n, Las Palmas de Gran Canaria, 35017, Spain; Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Canary Islands, Spain; Department of Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway.
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Pasmiño G, Paredes M, Silva H. Effects of High-Intensity Swimming Interval Training on Area, Perimeter, Circularity Index and Phenotype of Cardiac Mitochondrial Ultrastructure in Sprague Dawley Rats. Life (Basel) 2024; 14:984. [PMID: 39202726 PMCID: PMC11355701 DOI: 10.3390/life14080984] [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: 01/10/2024] [Revised: 02/22/2024] [Accepted: 02/23/2024] [Indexed: 09/03/2024] Open
Abstract
Physical inactivity impairs health by increasing morbidity. In childhood, modifiable risk factors associated with cardiovascular pathologies and related to mitochondrial function and structure are initiated by physical inactivity. The objective of this study was to analyze the effect of high-intensity swimming interval training (HIIT-swim) on cardiac mitochondrial ultrastructure in young Sprague Dawley rats compared with a sedentary group. Five-week-old Sprague Dawley rats (n = 18) were divided into a control group (C) (n = 6), a sedentary group (S) (n = 6) and an HIIT-swim group (H-s) (n = 6), the last of which performed HIIT-swim for 4 weeks. A mitochondrial ultrastructural evaluation was performed using transmission electron microscopy. In the H-s rats, mitochondrial areas and perimeters were found to be statistically significantly different from those of the C and S rats. In addition, no predominant intramitochondrial multifragmentation was observed in the mitochondria of H-s rats, but multifragmentation was evident in the mitochondria of S rats.
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Affiliation(s)
- Grace Pasmiño
- Programa de Doctorado en Ciencias Morfológicas, Facultad de Medicina, Universidad de La Frontera, Temuco 4811230, Chile;
- Laboratorio Fisiología del Ejercicio, Departamento de Ciencias Básicas, Facultad de Medicina, Universidad de La Frontera, Temuco 4811230, Chile
| | - Marco Paredes
- Laboratorio de Biología Celular, Departamento de Ciencias Básicas, Facultad de Medicina, Universidad de La Frontera, Temuco 4811230, Chile;
| | - Héctor Silva
- Laboratorio Fisiología del Ejercicio, Departamento de Ciencias Básicas, Facultad de Medicina, Universidad de La Frontera, Temuco 4811230, Chile
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Amar D, Gay NR, Jimenez-Morales D, Jean Beltran PM, Ramaker ME, Raja AN, Zhao B, Sun Y, Marwaha S, Gaul DA, Hershman SG, Ferrasse A, Xia A, Lanza I, Fernández FM, Montgomery SB, Hevener AL, Ashley EA, Walsh MJ, Sparks LM, Burant CF, Rector RS, Thyfault J, Wheeler MT, Goodpaster BH, Coen PM, Schenk S, Bodine SC, Lindholm ME. The mitochondrial multi-omic response to exercise training across rat tissues. Cell Metab 2024; 36:1411-1429.e10. [PMID: 38701776 PMCID: PMC11152996 DOI: 10.1016/j.cmet.2023.12.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 09/27/2023] [Accepted: 12/15/2023] [Indexed: 05/05/2024]
Abstract
Mitochondria have diverse functions critical to whole-body metabolic homeostasis. Endurance training alters mitochondrial activity, but systematic characterization of these adaptations is lacking. Here, the Molecular Transducers of Physical Activity Consortium mapped the temporal, multi-omic changes in mitochondrial analytes across 19 tissues in male and female rats trained for 1, 2, 4, or 8 weeks. Training elicited substantial changes in the adrenal gland, brown adipose, colon, heart, and skeletal muscle. The colon showed non-linear response dynamics, whereas mitochondrial pathways were downregulated in brown adipose and adrenal tissues. Protein acetylation increased in the liver, with a shift in lipid metabolism, whereas oxidative proteins increased in striated muscles. Exercise-upregulated networks were downregulated in human diabetes and cirrhosis. Knockdown of the central network protein 17-beta-hydroxysteroid dehydrogenase 10 (HSD17B10) elevated oxygen consumption, indicative of metabolic stress. We provide a multi-omic, multi-tissue, temporal atlas of the mitochondrial response to exercise training and identify candidates linked to mitochondrial dysfunction.
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Affiliation(s)
- David Amar
- Stanford University, Stanford, CA, USA; Insitro, San Francisco, CA, USA
| | | | | | | | | | | | | | - Yifei Sun
- Icahn School of Medicine at Mount Sinai, New York City, NY, USA
| | | | - David A Gaul
- Georgia Institute of Technology, Atlanta, GA, USA
| | | | | | - Ashley Xia
- National Institutes of Health, Bethesda, MD, USA
| | | | | | | | | | | | - Martin J Walsh
- Icahn School of Medicine at Mount Sinai, New York City, NY, USA
| | - Lauren M Sparks
- Translational Research Institute AdventHealth, Orlando, FL, USA
| | | | | | - John Thyfault
- University of Kansas Medical Center, Kansas City, KS, USA
| | | | | | - Paul M Coen
- Translational Research Institute AdventHealth, Orlando, FL, USA
| | - Simon Schenk
- University of California, San Diego, La Jolla, CA, USA
| | - Sue C Bodine
- Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
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Perelló-Amorós M, Fernández-Borràs J, Yu S, Sánchez-Moya A, García de la serrana D, Gutiérrez J, Blasco J. Improving the Aerobic Capacity in Fingerlings of European Sea Bass ( Dicentrarchus labrax) through Moderate and Sustained Exercise: A Metabolic Approach. Animals (Basel) 2024; 14:274. [PMID: 38254443 PMCID: PMC10812480 DOI: 10.3390/ani14020274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 01/08/2024] [Accepted: 01/12/2024] [Indexed: 01/24/2024] Open
Abstract
Sustained swimming induces beneficial effects on growth and energy metabolism in some fish species. However, the absence of a standardized exercise regimen that guarantees an optimal response to physical activity is due to the anatomical, behavioral, and physiological differences among species, and the different conditions of tests applied, which are especially notable for the early stages of cultured species. The objective of this study was to assess the growth and metabolic responses of European sea bass submitted to continuous and moderate exercise exposure, selecting a practical swimming speed from swimming tests of groups of five fingerlings. The exercise-effects trial was carried out with 600 sea bass fingerlings (3-5 g body weight) distributed in two groups (control: voluntary swimming; exercised: under sustained swimming at 1.5 body lengths·s-1). After 6 weeks, growth parameters and proximal composition of both muscles were not altered by sustained swimming, but an increased synthetic capacity (increased RNA/DNA ratio) and more efficient use of proteins (decreased ΔN15) were observed in white muscle. The gene expression of mitochondrial proteins in white and red muscle was not affected by exercise, except for ucp3, which increased. The increase of UCP3 and Cox4 protein expression, as well as the higher COX/CS ratio of enzyme activity in white muscle, pointed out an enhanced oxidative capacity in this tissue during sustained swimming. In the protein expression of red muscle, only CS increased. All these metabolic adaptations to sustained exercise were also reflected in an enhanced maximum metabolic rate (MMR) with higher aerobic scope (AMS) of exercised fish in comparison to the non-trained fish, during a swimming test. These results demonstrated that moderate sustained swimming applied to sea bass fingerlings can improve the physical fitness of individuals through the enhancement of their aerobic capacities.
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Affiliation(s)
| | | | | | | | | | | | - Josefina Blasco
- Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Av. Diagonal 643, 08028 Barcelona, Spain; (M.P.-A.); (J.F.-B.); (S.Y.); (A.S.-M.); (D.G.d.l.s.); (J.G.)
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10
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Li S, Wang P, Cai Z, Jiang W, Xin X, Wang X, Zhou X. Correlates of physical activity levels, muscle strength, working memory, and cognitive function in older adults. Front Aging Neurosci 2023; 15:1283864. [PMID: 38161587 PMCID: PMC10757612 DOI: 10.3389/fnagi.2023.1283864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 11/29/2023] [Indexed: 01/03/2024] Open
Abstract
Objective To explore the relationship between physical activity level, muscle strength, working memory and cognitive function in older adults. Methods A cross-sectional research design was employed to recruit 120 older adults individuals aged 70 and above. Participants were asked to complete the International Physical Activity Questionnaire-Short Form and the Montreal Cognitive Assessment Scale. Data on variables such as grip strength and performance on the N-back task were collected. Data analysis involved the use of independent samples t-tests, χ2 tests, linear regression analysis, Pearson correlation analysis, and one-way analysis of variance (ANOVA). Results The detection rate of cognitive dysfunction in older adults was 53.211%; 1-back correct rate had an explanatory power of 11.6% for the cognitive function scores of older adults (R2 = 0.116, p < 0.001); grip strength showed a significant positive correlation with 1-back correct rate (r = 0.417, p < 0.001), and was significantly correlated with the 0-back response time (r = -0.478), 1 -back response time (r = -0.441) were significantly negatively correlated (p < 0.001); physical activity level was significantly positively correlated with grip strength (r = 0.559, p < 0.001), and the difference in grip strength among older adults with different physical activity levels was statistically significant (F = 19.685, p < 0.001). Conclusion Physical activity level, muscle strength, working memory, and cognitive function are closely related in older adults, and the relational pathway of physical activity → muscle strength → working memory → cognitive function may serve as a useful addition to promote the field of cognitive research in older adults. To identify and prevent cognitive decline in older adults, physical activity questionnaires, grip strength tests, and 1-back task tests can be extended to nursing homes and communities.
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Affiliation(s)
- Shufan Li
- School of Physical Education, Shanghai University of Sport, Shanghai, China
| | - Peng Wang
- School of Physical Education, Shanghai University of Sport, Shanghai, China
| | - Zhidong Cai
- Department of Physical Education, Suzhou University of Science and Technology, Suzhou, China
| | - Wanting Jiang
- School of Physical Education, Shanghai University of Sport, Shanghai, China
| | - Xin Xin
- School of Physical Education, Shanghai University of Sport, Shanghai, China
| | - Xing Wang
- School of Physical Education, Shanghai University of Sport, Shanghai, China
| | - Xiaojing Zhou
- School of Sports and Health of Shanghai Lixin University of Accounting and Finance, Shanghai, China
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Wang JF, Wen DT, Wang SJ, Gao YH, Yin XY. Muscle-specific overexpression of Atg2 gene and endurance exercise delay age-related deteriorations of skeletal muscle and heart function via activating the AMPK/Sirt1/PGC-1α pathway in male Drosophila. FASEB J 2023; 37:e23214. [PMID: 37773768 DOI: 10.1096/fj.202301312r] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 08/29/2023] [Accepted: 09/08/2023] [Indexed: 10/01/2023]
Abstract
Atg2 is a key gene in autophagy formation and plays an important role in regulating aging progress. Exercise is an important tool to resist oxidative stress in cells and delay muscle aging. However, the relationship between exercise and the muscle Atg2 gene in regulating skeletal muscle aging remains unclear. Here, overexpression or knockdown of muscle Atg2 gene was achieved by constructing the AtgUAS/MhcGal4 system in Drosophila, and these flies were also subjected to an exercise intervention for 2 weeks. The results showed that both overexpression of Atg2 and exercise significantly increased the climbing speed, climbing endurance, cardiac function, and lifespan of aging flies. They also significantly up-regulated the expression of muscle Atg2, AMPK, Sirt1, and PGC-1α genes, and they significantly reduced muscle malondialdehyde and triglyceride. These positive benefits were even more pronounced when the two were combined. However, the effects of Atg2 knockdown on skeletal muscle, heart, and lifespan were reversed compared to its overexpression. Importantly, exercise ameliorated age-related changes induced by Atg2 knockdown. Therefore, current results confirmed that both overexpression of muscle Atg2 and exercise delayed age-related deteriorations of skeletal muscle, the heart function, and lifespan, and exercise could also reverse age-related changes induced by Atg2 knockdown. The molecular mechanism is related to the overexpression of the Atg2 gene and exercise, which increase the activity of the AMPK/Sirt1/PGC-1α pathway, oxidation and antioxidant balance, and lipid metabolism in aging muscle.
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Affiliation(s)
- Jing-Feng Wang
- School of Physical Education, Ludong University, Yantai, P.R. China
| | - Deng-Tai Wen
- School of Physical Education, Ludong University, Yantai, P.R. China
| | - Shi-Jie Wang
- School of Physical Education, Ludong University, Yantai, P.R. China
| | - Ying-Hui Gao
- School of Physical Education, Ludong University, Yantai, P.R. China
| | - Xin-Yuan Yin
- School of Physical Education, Ludong University, Yantai, P.R. China
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12
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Pengam M, Goanvec C, Moisan C, Simon B, Albacète G, Féray A, Guernec A, Amérand A. Moderate intensity continuous versus high intensity interval training: Metabolic responses of slow and fast skeletal muscles in rat. PLoS One 2023; 18:e0292225. [PMID: 37792807 PMCID: PMC10550171 DOI: 10.1371/journal.pone.0292225] [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] [Received: 02/03/2023] [Accepted: 09/15/2023] [Indexed: 10/06/2023] Open
Abstract
The healthy benefits of regular physical exercise are mainly mediated by the stimulation of oxidative and antioxidant capacities in skeletal muscle. Our understanding of the cellular and molecular responses involved in these processes remain often uncomplete particularly regarding muscle typology. The main aim of the present study was to compare the effects of two types of exercise training protocol: a moderate-intensity continuous training (MICT) and a high-intensity interval training (HIIT) on metabolic processes in two muscles with different typologies: soleus and extensor digitorum longus (EDL). Training effects in male Wistar rats were studied from whole organism level (maximal aerobic speed, morphometric and systemic parameters) to muscle level (transcripts, protein contents and enzymatic activities involved in antioxidant defences, aerobic and anaerobic metabolisms). Wistar rats were randomly divided into three groups: untrained (UNTR), n = 7; MICT, n = 8; and HIIT, n = 8. Rats of the MICT and HIIT groups ran five times a week for six weeks at moderate and high intensity, respectively. HIIT improved more than MICT the endurance performance (a trend to increased maximal aerobic speed, p = 0.07) and oxidative capacities in both muscles, as determined through protein and transcript assays (AMPK-PGC-1α signalling pathway, antioxidant defences, mitochondrial functioning and dynamics). Whatever the training protocol, the genes involved in these processes were largely more significantly upregulated in soleus (slow-twitch fibres) than in EDL (fast-twitch fibres). Solely on the basis of the transcript changes, we conclude that the training protocols tested here lead to specific muscular responses.
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Affiliation(s)
| | | | | | | | | | - Annie Féray
- EA 4324 ORPHY, Université de Brest, Brest, France
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13
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Martínez-Montoro JI, Benítez-Porres J, Tinahones FJ, Ortega-Gómez A, Murri M. Effects of exercise timing on metabolic health. Obes Rev 2023; 24:e13599. [PMID: 37416977 DOI: 10.1111/obr.13599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 04/12/2023] [Accepted: 06/12/2023] [Indexed: 07/08/2023]
Abstract
The increasing prevalence of metabolic syndrome is associated with major health and socioeconomic consequences. Currently, physical exercise, together with dietary interventions, is the mainstay of the treatment of obesity and related metabolic complications. Although exercise training includes different modalities, with variable intensity, duration, volume, or frequency, which may have a distinct impact on several characteristics related to metabolic syndrome, the potential effects of exercise timing on metabolic health are yet to be fully elucidated. Remarkably, promising results with regard to this topic have been reported in the last few years. Similar to other time-based interventions, including nutritional therapy or drug administration, time-of-day-based exercise may become a useful approach for the management of metabolic disorders. In this article, we review the role of exercise timing in metabolic health and discuss the potential mechanisms that could drive the metabolic-related benefits of physical exercise performed in a time-dependent manner.
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Affiliation(s)
- José Ignacio Martínez-Montoro
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Málaga, Spain
- Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Málaga, Spain
- Faculty of Medicine, University of Málaga, Málaga, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y la Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain
| | - Javier Benítez-Porres
- Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Málaga, Spain
- Physical Education and Sport, Faculty of Medicine, University of Málaga, Málaga, Spain
| | - Francisco J Tinahones
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Málaga, Spain
- Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Málaga, Spain
- Faculty of Medicine, University of Málaga, Málaga, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y la Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain
| | - Almudena Ortega-Gómez
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Málaga, Spain
- Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Málaga, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y la Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain
| | - Mora Murri
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Málaga, Spain
- Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Málaga, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y la Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain
- Heart Area Clinical Management Unit, Virgen de la Victoria University Hospital, Málaga, Spain
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14
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Resistance training prevents dynamics and mitochondrial respiratory dysfunction in vastus lateralis muscle of ovariectomized rats. Exp Gerontol 2023; 173:112081. [PMID: 36608776 DOI: 10.1016/j.exger.2023.112081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 01/02/2023] [Indexed: 01/05/2023]
Abstract
To investigate whether ovariectomy affects mitochondrial respiratory function, gene expression of the biogenesis markers and mitochondrial dynamics of the vastus lateralis muscle, female Wistar rats divided into ovariectomized (OVX) and intact (INT) groups were kept sedentary (SED) or submitted to resistance training (RT) performed for thirteen weeks on a vertical ladder in which animals climbed with a workload apparatus. RT sessions were performed with four climbs with 65, 85, 95, and 100 % of the rat's previous maximum workload. Mitochondrial Respiratory Function data were obtained by High-resolution respirometry. Gene expression of FIS1, MFN1 and PGC1-α was evaluated by real-time PCR. There was a decrease on oxidative phosphorylation capacity in OVX-SED compared to other groups. Trained groups presented increase on oxidative phosphorylation capacity when compared to sedentary groups. For respiratory control ratio (RCR), OVX-SED presented lower values when compared to INT-SED and to trained groups. Trained groups presented RCR values higher compared to INT-SED. Exercise increased the values of FIS1, MFN1 and PGC1-α expression compared to OVX-SED. Our results demonstrated that in the absence of ovarian hormones, there is a great decrease in oxidative phosphorylation and electron transfer system capacities of sedentary animals. RT was able to increase the expression of genes related to mitochondrial dynamics markers, reversing the condition determined by ovariectomy.
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15
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Alway SE, Paez HG, Pitzer CR, Ferrandi PJ, Khan MM, Mohamed JS, Carson JA, Deschenes MR. Mitochondria transplant therapy improves regeneration and restoration of injured skeletal muscle. J Cachexia Sarcopenia Muscle 2023; 14:493-507. [PMID: 36604839 PMCID: PMC9891964 DOI: 10.1002/jcsm.13153] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 11/17/2022] [Accepted: 11/29/2022] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Injection of exogenous mitochondria has been shown to improve the ischaemia-damaged myocardium, but the effect of mitochondrial transplant therapy (MTT) to restore skeletal muscle mass and function has not been tested following neuromuscular injury. Therefore, we tested the hypothesis that MTT would improve the restoration of muscle function after injury. METHODS BaCl2 was injected into the gastrocnemius muscle of one limb of 8-12-week-old C57BL/6 mice to induce damage without injury to the resident stem cells. The contralateral gastrocnemius muscle was injected with phosphate-buffered saline (PBS) and served as the non-injured intra-animal control. Mitochondria were isolated from donor mice. Donor mitochondria were suspended in PBS or PBS without mitochondria (sham treatment) and injected into the tail vein of BaCl2 injured mice 24 h after the initial injury. Muscle repair was examined 7, 14 and 21 days after injury. RESULTS MTT did not increase systemic inflammation in mice. Muscle mass 7 days following injury was 21.9 ± 2.1% and 17.4 ± 1.9% lower (P < 0.05) in injured as compared with non-injured intra-animal control muscles in phosphate-buffered saline (PBS)- and MTT-treated animals, respectively. Maximal plantar flexor muscle force was significantly lower in injured as compared with uninjured muscles of PBS-treated (-43.4 ± 4.2%, P < 0.05) and MTT-treated mice (-47.7 ± 7.3%, P < 0.05), but the reduction in force was not different between the experimental groups. The percentage of collagen and other non-contractile tissue in histological muscle cross sections, was significantly greater in injured muscles of PBS-treated mice (33.2 ± 0.2%) compared with MTT-treated mice (26.5 ± 0.2%) 7 days after injury. Muscle wet weight and maximal muscle force from injured MTT-treated mice had recovered to control levels by 14 days after the injury. However, muscle mass and force had not improved in PBS-treated animals by 14 days after injury. The non-contractile composition of the gastrocnemius muscle tissue cross sections was not different between control, repaired PBS-treated and repaired MTT-treated mice 14 days after injury. By 21 days following injury, PBS-treated mice had fully restored gastrocnemius muscle mass of the injured muscle to that of the uninjured muscle, although maximal plantar flexion force was still 19.4 ± 3.7% (P < 0.05) lower in injured/repaired gastrocnemius as compared with uninjured intra-animal control muscles. CONCLUSIONS Our results suggest that systemic mitochondria delivery can enhance the rate of muscle regeneration and restoration of muscle function following injury.
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Affiliation(s)
- Stephen E Alway
- Laboratory of Muscle Biology and Sarcopenia, Division of Regenerative and Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN, USA.,Center for Muscle, Metabolism and Neuropathology, Division of Regenerative and Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN, USA.,Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.,Tennessee Institute of Regenerative Medicine, Memphis, TN, USA
| | - Hector G Paez
- Laboratory of Muscle Biology and Sarcopenia, Division of Regenerative and Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN, USA.,Center for Muscle, Metabolism and Neuropathology, Division of Regenerative and Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN, USA.,Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.,Integrated Biomedical Sciences Graduate Program, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Christopher R Pitzer
- Laboratory of Muscle Biology and Sarcopenia, Division of Regenerative and Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN, USA.,Center for Muscle, Metabolism and Neuropathology, Division of Regenerative and Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN, USA.,Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.,Integrated Biomedical Sciences Graduate Program, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Peter J Ferrandi
- Center for Muscle, Metabolism and Neuropathology, Division of Regenerative and Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN, USA.,Integrated Biomedical Sciences Graduate Program, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, TN, USA.,Laboratory of Muscle and Nerve, Department of Diagnostic and Health Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Mohammad Moshahid Khan
- Center for Muscle, Metabolism and Neuropathology, Division of Regenerative and Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN, USA.,Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Junaith S Mohamed
- Center for Muscle, Metabolism and Neuropathology, Division of Regenerative and Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN, USA.,Tennessee Institute of Regenerative Medicine, Memphis, TN, USA.,Laboratory of Muscle and Nerve, Department of Diagnostic and Health Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN, USA
| | - James A Carson
- Center for Muscle, Metabolism and Neuropathology, Division of Regenerative and Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN, USA.,Tennessee Institute of Regenerative Medicine, Memphis, TN, USA.,Integrative Muscle Biology Laboratory, Division of Regenerative and Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN, USA
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16
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Amar D, Gay NR, Jimenez-Morales D, Beltran PMJ, Ramaker ME, Raja AN, Zhao B, Sun Y, Marwaha S, Gaul D, Hershman SG, Xia A, Lanza I, Fernandez FM, Montgomery SB, Hevener AL, Ashley EA, Walsh MJ, Sparks LM, Burant CF, Rector RS, Thyfault J, Wheeler MT, Goodpaster BH, Coen PM, Schenk S, Bodine SC, Lindholm ME, MoTrPAC Study Group. The mitochondrial multi-omic response to exercise training across tissues. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.01.13.523698. [PMID: 36711881 PMCID: PMC9882193 DOI: 10.1101/2023.01.13.523698] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Mitochondria are adaptable organelles with diverse cellular functions critical to whole-body metabolic homeostasis. While chronic endurance exercise training is known to alter mitochondrial activity, these adaptations have not yet been systematically characterized. Here, the Molecular Transducers of Physical Activity Consortium (MoTrPAC) mapped the longitudinal, multi-omic changes in mitochondrial analytes across 19 tissues in male and female rats endurance trained for 1, 2, 4 or 8 weeks. Training elicited substantial changes in the adrenal gland, brown adipose, colon, heart and skeletal muscle, while we detected mild responses in the brain, lung, small intestine and testes. The colon response was characterized by non-linear dynamics that resulted in upregulation of mitochondrial function that was more prominent in females. Brown adipose and adrenal tissues were characterized by substantial downregulation of mitochondrial pathways. Training induced a previously unrecognized robust upregulation of mitochondrial protein abundance and acetylation in the liver, and a concomitant shift in lipid metabolism. The striated muscles demonstrated a highly coordinated response to increase oxidative capacity, with the majority of changes occurring in protein abundance and post-translational modifications. We identified exercise upregulated networks that are downregulated in human type 2 diabetes and liver cirrhosis. In both cases HSD17B10, a central dehydrogenase in multiple metabolic pathways and mitochondrial tRNA maturation, was the main hub. In summary, we provide a multi-omic, cross-tissue atlas of the mitochondrial response to training and identify candidates for prevention of disease-associated mitochondrial dysfunction.
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Affiliation(s)
| | | | | | | | | | | | | | - Yifei Sun
- Icahn School of Medicine at Mount Sinai, New York City, NY
| | | | | | | | - Ashley Xia
- National Institutes of Health, Bethesda, MD
| | | | | | | | | | | | - Martin J Walsh
- Icahn School of Medicine at Mount Sinai, New York City, NY
| | - Lauren M Sparks
- AdventHealth Translational Research Institute for Metabolism and Diabetes, Orlando, FL
| | | | | | - John Thyfault
- University of Kansas Medical Center, Kansas City, KS
| | | | - Bret H. Goodpaster
- AdventHealth Translational Research Institute for Metabolism and Diabetes, Orlando, FL
| | - Paul M. Coen
- AdventHealth Translational Research Institute for Metabolism and Diabetes, Orlando, FL
| | - Simon Schenk
- University of California, San Diego, La Jolla, CA
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17
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Stevanović-Silva J, Beleza J, Coxito P, Oliveira PJ, Ascensão A, Magalhães J. Gestational Exercise Antagonises the Impact of Maternal High-Fat High-Sucrose Diet on Liver Mitochondrial Alterations and Quality Control Signalling in Male Offspring. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:1388. [PMID: 36674144 PMCID: PMC9858977 DOI: 10.3390/ijerph20021388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/03/2023] [Accepted: 01/09/2023] [Indexed: 06/17/2023]
Abstract
Maternal high-caloric nutrition and related gestational diabetes mellitus (GDM) are relevant modulators of the intrauterine environment, increasing the risk of liver metabolic alterations in mothers and offspring. In contrast, as a non-pharmacological approach against metabolic disorders, exercise is highly recommended in GDM treatment. We analysed whether gestational exercise (GE) protects mothers from diet-induced GDM metabolic consequences and mitigates liver mitochondrial deleterious alterations in their 6-week-old male offspring. Female Sprague Dawley rats were fed with control or high-fat high-sucrose (HFHS) diet and kept sedentary or submitted to GE. Male offspring were sedentary and fed with control diet. Sedentary HFHS mothers and their offspring showed impaired hepatic mitochondrial biogenesis and morphological evidence of mitochondrial remodelling. In contrast, GE-related beneficial effects were demonstrated by upregulation of mitochondrial biogenesis signalling markers and mitochondrial fusion proteins and downregulation of mitochondrial fission protein. Alterations in miR-34a, miR-130b, and miR-494, associated with epigenetic regulation of mitochondrial biogenesis, suggested that GE is a more critical modulator of intergenerational changes in miRs expression than the maternal diet. Our data showed that GE positively modulated the altered hepatic mitochondrial biogenesis and dynamics markers and quality control signalling associated with maternal HFHS-diet-related GDM in mothers and offspring.
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Affiliation(s)
- Jelena Stevanović-Silva
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, 4200-450 Porto, Portugal
| | - Jorge Beleza
- Department of Cell Biology, Physiology & Immunology, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain
| | - Pedro Coxito
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, 4200-450 Porto, Portugal
| | - Paulo J. Oliveira
- CNC—Center for Neuroscience and Cell Biology, CIBB—Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal
| | - António Ascensão
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, 4200-450 Porto, Portugal
| | - José Magalhães
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, 4200-450 Porto, Portugal
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18
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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: 16] [Impact Index Per Article: 5.3] [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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19
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Sawada T, Okawara H, Nakashima D, Ikeda K, Nagahara J, Fujitsuka H, Hoshino S, Maeda Y, Katsumata Y, Nakamura M, Nagura T. Constant Load Pedaling Exercise Combined with Electrical Muscle Stimulation Leads to an Early Increase in Sweat Lactate Levels. SENSORS (BASEL, SWITZERLAND) 2022; 22:9585. [PMID: 36559954 PMCID: PMC9784187 DOI: 10.3390/s22249585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 12/06/2022] [Accepted: 12/06/2022] [Indexed: 06/17/2023]
Abstract
A novel exercise modality combined with electrical muscle stimulation (EMS) has been reported to increase cardiovascular and metabolic responses, such as blood lactate concentration. We aimed to examine the effect of constant load pedaling exercise, combined with EMS, by non-invasively and continuously measuring sweat lactate levels. A total of 22 healthy young men (20.7 ± 0.8 years) performed a constant load pedaling exercise for 20 min at 125% of the pre-measured ventilatory work threshold with (EMS condition) and without (control condition) EMS stimulation. Blood lactate concentration was measured by blood samples obtained from the earlobe every minute. Sweat lactate was monitored in real time using a sensor placed on the forearm. The sweat lactate threshold (sLT) was defined as the point of increase in sweat lactate. sLT occurred significantly earlier in the EMS condition than in the control condition. In the single regression analysis, the difference in sLT between the two conditions, as the independent variable, was a significant predictor of the difference in blood lactate concentrations at the end of the exercise (p < 0.05, r = −0.52). Sweat lactate measurement may be a noninvasive and simple alternative to blood lactate measurement to determine the effectiveness of exercise combined with EMS.
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Affiliation(s)
- Tomonori Sawada
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Hiroki Okawara
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Daisuke Nakashima
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Kaito Ikeda
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Joji Nagahara
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Haruki Fujitsuka
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Sosuke Hoshino
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Yuta Maeda
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Yoshinori Katsumata
- Institute for Integrated Sports Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Masaya Nakamura
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Takeo Nagura
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
- Department of Clinical Biomechanics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
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20
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Diet, Exercise, and the Metabolic Syndrome: Enrollment of the Mitochondrial Machinery. Nutrients 2022; 14:nu14214519. [DOI: 10.3390/nu14214519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 10/21/2022] [Indexed: 11/17/2022] Open
Abstract
Metabolic syndrome (MS), a cluster of metabolic risk factors, ranging from abdominal obesity, dyslipidaemia, hypertension, type 2 diabetes and non-alcoholic fatty liver disease [...]
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21
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Ra SG, Nakagawa H, Tomiga Y, Iizawa H, Nakashima S, Higaki Y, Kawanaka K. Effects of Dietary Vitamin D Deficiency on Markers of Skeletal Muscle Mitochondrial Biogenesis and Dynamics. J Nutr Sci Vitaminol (Tokyo) 2022; 68:243-249. [PMID: 36047095 DOI: 10.3177/jnsv.68.243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
We examined the effects of dietary vitamin D deficiency on markers of mitochondrial biogenesis and dynamics in rat soleus muscle. Male Wistar rats were fed a chow with no vitamin D (No-D; 0 IU/kg) or a moderate dose (Mod-D; 2,000 IU/kg) of vitamin D chow for 8 wk. Compared to the Mod-D group, at 8 wk the No-D group showed significantly lower serum 25(OH)D levels. Although vitamin D deficiency had no effect on body composition, the No-D rats showed significantly decreased levels of PGC-1α, a marker of skeletal muscle mitochondrial biogenesis, and DRP1, a marker of skeletal muscle mitochondrial fission. The change in the PGC-1α protein expression and the serum 25(OH)D concentrations were significantly correlated. The change in DRP1 protein expression and the serum 25(OH)D concentrations tended to be correlated. There was no significant between-group difference in markers of mitochondrial fusion (MFN2 and OPA1) and mitophagy (PARKIN) in soleus muscle, and no relationship with serum 25(OH)D concentrations. Collectively our findings suggest that dietary vitamin D deficiency decreased PGC-1α and DRP1 protein expression in rat soleus muscle.
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Affiliation(s)
- Song-Gyu Ra
- Laboratory of Exercise Nutrition and Biochemistry, Faculty of Sports and Health Science, Fukuoka University.,Fukuoka Univerity Institute for Physical Activity.,Institute of Liberal Arts and Sciences, Tokushima University
| | - Hironari Nakagawa
- Laboratory of Exercise Nutrition and Biochemistry, Faculty of Sports and Health Science, Fukuoka University
| | - Yuki Tomiga
- Fukuoka Univerity Institute for Physical Activity.,Laboratory of Exercise Physiology, Faculty of Sports and Health Science, Fukuoka University.,Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University.,Japan Society for the Promotion of Science
| | - Hiroki Iizawa
- Laboratory of Exercise Nutrition and Biochemistry, Faculty of Sports and Health Science, Fukuoka University
| | | | - Yasuki Higaki
- Fukuoka Univerity Institute for Physical Activity.,Laboratory of Exercise Physiology, Faculty of Sports and Health Science, Fukuoka University
| | - Kentaro Kawanaka
- Laboratory of Exercise Nutrition and Biochemistry, Faculty of Sports and Health Science, Fukuoka University.,Fukuoka Univerity Institute for Physical Activity
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22
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Zhang B, Bi Q, Huang S, Lv S, Zong X, Wang M, Ji X. Baoyuan Jiedu decoction alleviating cancer cachexia–Induced muscle atrophy by regulating muscle mitochondrial function in ApcMin/+ mice. Front Pharmacol 2022; 13:914597. [PMID: 36060011 PMCID: PMC9437209 DOI: 10.3389/fphar.2022.914597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 07/15/2022] [Indexed: 11/13/2022] Open
Abstract
Cancer cachexia is a complex syndrome that leads to an ongoing loss of skeletal muscle mass in many malignant tumors. Our previous studies have evaluated the effectiveness of Baoyuan Jiedu decoction (BJD) in alleviating cancer-induced muscle atrophy. However, the mechanisms of BJD regulating muscle atrophy could not be fully understood. Therefore, we further investigated the mechanisms of BJD mitigating muscle atrophy both in an ApcMin/+ mouse model and the Lewis-conditioned medium–induced C2C12 myotube atrophy model. We confirmed the quality of BJD extracts by HPLC. In an In vivo study, body weight loss and muscle atrophy were alleviated with BJD treatment. GO analysis suggested that ATP metabolism and mitochondria were involved. The results of the electron microscope show that BJD treatment may have a healing effect on mitochondrial structure. Moreover, ATP content and mitochondrial numbers were improved with BJD treatment. Furthermore, both in vivo and in vitro, we demonstrated that the BJD treatment could improve mitochondrial function owing to the increased number of mitochondria, balanced dynamic, and regulation of the electron transport chain according to the protein and mRNA expressions. In addition, oxidative stress caused by mitochondrial dysfunction was ameliorated by BJD treatment in ApcMin/+ mice. Consequently, our study provides proof for BJD treatment alleviating cancer cachexia–induced muscle atrophy by modulating mitochondrial function in ApcMin/+ mice.
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Affiliation(s)
- Beiying Zhang
- School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qianyu Bi
- School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
| | - Shengqi Huang
- School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
| | - Siyuan Lv
- School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xin Zong
- Weifang Nursing Vocational College, Weifang, China
| | - Mengran Wang
- Department of Pediatrics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xuming Ji
- School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
- Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
- *Correspondence: Xuming Ji,
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23
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Peñailillo L, Valladares-Ide D, Jannas-Velas S, Flores-Opazo M, Jalón M, Mendoza L, Nuñez I, Diaz-Patiño O. Effects of eccentric, concentric and eccentric/concentric training on muscle function and mass, functional performance, cardiometabolic health, quality of life and molecular adaptations of skeletal muscle in COPD patients: a multicentre randomised trial. BMC Pulm Med 2022; 22:278. [PMID: 35854255 PMCID: PMC9297587 DOI: 10.1186/s12890-022-02061-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 07/04/2022] [Indexed: 11/12/2022] Open
Abstract
Background Chronic obstructive pulmonary disease (COPD) is the third cause of death worldwide. COPD is characterised by dyspnoea, limited exercise tolerance, and muscle dysfunction. Muscle dysfunction has been linked to dysregulation between muscle protein synthesis, myogenesis and degradation mechanisms. Conventional concentric cycling has been shown to improve several clinical outcomes and reduce muscle wasting in COPD patients. Eccentric cycling is a less explored exercise modality that allows higher training workloads imposing lower cardio-metabolic demand during exercise, which has shown to induce greater muscle mass and strength gains after training. Interestingly, the combination of eccentric and concentric cycling training has scarcely been explored. The molecular adaptations of skeletal muscle after exercise interventions in COPD have shown equivocal results. The mechanisms of muscle wasting in COPD and whether it can be reversed by exercise training are unclear. Therefore, this study aims two-fold: (1) to compare the effects of 12 weeks of eccentric (ECC), concentric (CONC), and combined eccentric/concentric (ECC/CONC) cycling training on muscle mass and function, cardiometabolic health, physical activity levels and quality of life in severe COPD patients; and (2) to examine the molecular adaptations regulating muscle growth after training, and whether they occur similarly in specific muscle fibres (i.e., I, IIa and IIx). Methods Study 1 will compare the effects of 12 weeks of CONC, ECC, versus ECC/CONC training on muscle mass and function, cardiometabolic health, levels of physical activity and quality of life of severe COPD patients using a multicentre randomised trial. Study 2 will investigate the effects of these training modalities on the molecular adaptations regulating muscle protein synthesis, myogenesis and muscle degradation in a subgroup of patients from Study 1. Changes in muscle fibres morphology, protein content, genes, and microRNA expression involved in skeletal muscle growth will be analysed in specific fibre-type pools. Discussion We aim to demonstrate that a combination of eccentric and concentric exercise could maximise the improvements in clinical outcomes and may be ideal for COPD patients. We also expect to unravel the molecular mechanisms underpinning muscle mass regulation after training in severe COPD patients. Trial Registry: Deutshches Register Klinischer Studien; Trial registration: DRKS00027331; Date of registration: 12 January 2022. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00027331.
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Affiliation(s)
- Luis Peñailillo
- Exercise and Rehabilitation Sciences Laboratory, School of Physical Therapy, Faculty of Rehabilitation Sciences, Universidad Andres Bello, 700 Fernández Concha, Las Condes, 7591538, Santiago, Chile.
| | - Denisse Valladares-Ide
- Long Active Life Laboratory, Instituto de Ciencias de la Salud, Universidad de O'Higgins, Rancagua, Chile
| | - Sebastián Jannas-Velas
- Long Active Life Laboratory, Instituto de Ciencias de la Salud, Universidad de O'Higgins, Rancagua, Chile
| | | | | | - Laura Mendoza
- Respiratory Unit, Departamento de Medicina, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - Ingrid Nuñez
- Department of Pulmonary Diseases, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago, Chile.,Department of Critical Care, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago, Chile
| | - Orlando Diaz-Patiño
- Department of Pulmonary Diseases, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago, Chile.,Department of Critical Care, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago, Chile
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24
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Morena da Silva F, Rosa-Caldwell ME, Schrems ER, Martinez L, Amos MG, Lim S, Cabrera AR, Brown JL, Washington TA, Greene NP. PGC-1α overexpression is not sufficient to mitigate cancer cachexia in either male or female mice. Appl Physiol Nutr Metab 2022; 47:933-948. [PMID: 35700525 DOI: 10.1139/apnm-2022-0086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Cancer-cachexia accounts for 20-40% of cancer-related deaths. Mitochondrial aberrations have been shown to precede muscle atrophy in different atrophy models, including cancer. Therefore, this study investigated potential protection from the cachectic phenotype through overexpression of PGC-1α. First, to establish potential of mitochondria-based approaches we showed that the mitochondrial antioxidant mitoTEMPO attenuates myotube atrophy induced by Lewis Lung Carcinoma (LLC) cell conditioned media. Next, cachexia was induced in muscle specific PGC-1α overexpressing (MCK-PCG1α) or wildtype (WT) littermate mice by LLC implantation. MCK-PCG1α did not protect LLC-induced muscle mass loss. In plantaris, Atrogin mRNA content was 6.2-fold and ~11-fold greater in WT-LLC vs. WT-PBS for males and females, respectively (p<0.05). MitoTimer red:green ratio for male PGC was ~65% higher than WT groups (p<0.05), with ~3-fold more red puncta in LLC than PBS (p<0.05). Red:green ratio was ~56% lower in females WT-LLC vs. PGC-LLC (p<0.05). In females, no change in red puncta was noted across conditions. Lc3 mRNA content was ~ 73% and 2-fold higher in male and female LLC mice respectively vs. PBS (p<0.05). While MitoTEMPO could mitigate cancer-induced atrophy in vitro, PGC1α overexpression was insufficient to protect muscle mass and mitochondrial health in vivo despite mitigation of cachexia-associated signaling pathways.
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Affiliation(s)
| | | | - Eleanor R Schrems
- University of Arkansas Fayetteville, 3341, Fayetteville, Arkansas, United States;
| | - Lauren Martinez
- University of Arkansas Fayetteville, 3341, HHPR, Fayetteville, Arkansas, United States;
| | - Madeline G Amos
- University of Arkansas Fayetteville, 3341, HHPR, Fayetteville, Arkansas, United States;
| | - Seongkyun Lim
- University of Arkansas Fayetteville, 3341, HHPR, Fayetteville, Arkansas, United States;
| | - Ana Regina Cabrera
- University of Arkansas Fayetteville, 3341, HHPR, Fayetteville, Arkansas, United States;
| | - Jacob L Brown
- University of Arkansas Fayetteville, 3341, Health, Human Performance and Recreation, Fayetteville, Arkansas, United States;
| | - Tyrone A Washington
- University of Arkansas Fayetteville, 3341, Health, Human Performance, and Recreation, Fayetteville, Arkansas, United States;
| | - Nicholas P Greene
- University of Arkansas Fayetteville, 3341, Health, Human Performance and Recreation, Fayetteville, Arkansas, United States;
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25
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Cunningham RP, Moore MP, Dashek RJ, Meers GM, Jepkemoi V, Takahashi T, Vieira-Potter VJ, Kanaley JA, Booth FW, Rector RS. Hepatocyte-specific eNOS deletion impairs exercise-induced adaptations in hepatic mitochondrial function and autophagy. Obesity (Silver Spring) 2022; 30:1066-1078. [PMID: 35357089 PMCID: PMC9050943 DOI: 10.1002/oby.23414] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 01/24/2022] [Accepted: 02/11/2022] [Indexed: 12/20/2022]
Abstract
OBJECTIVE Endothelial nitric oxide synthase (eNOS) is a potential mediator of exercise-induced hepatic mitochondrial adaptations. METHODS Here, male and female hepatocyte-specific eNOS knockout (eNOShep-/- ) and intact hepatic eNOS (eNOSfl/fl ) mice performed voluntary wheel-running exercise (EX) or remained in sedentary cage conditions for 10 weeks. RESULTS EX resolved the exacerbated hepatic steatosis in eNOShep-/- male mice. Elevated hydrogen peroxide emission (~50% higher in eNOShep-/- vs. eNOSfl/fl mice) was completely ablated with EX. Interestingly, EX increased [1-14 C] palmitate oxidation in eNOSfl/fl male mice, but this was blunted in the eNOShep-/- male mice. eNOShep-/- mice had lower markers of the energy sensors AMP-activated protein kinase (AMPK)/phospho- (p)AMPK and mammalian target of rapamycin (mTOR) and p-mTOR, as well as the autophagy initiators serine/threonine-protein kinase ULK1 and pULK1, compared with eNOSfl/fl mice. Females showed elevated electron transport chain protein content and markers of mitochondrial biogenesis (transcription factor A, mitochondrial, peroxisome proliferator-activated receptor-gamma coactivator 1α). CONCLUSIONS Collectively, this study demonstrates for the first time, to the authors' knowledge, the requirement of eNOS in hepatocytes in the EX-induced increases in hepatic fatty acid oxidation in male mice. Deletion of eNOS in hepatocytes also appears to impair the energy-sensing ability of the cell and inhibit the activation of the autophagy initiating factor ULK1. These data uncover the important and novel role of hepatocyte eNOS in EX-induced hepatic mitochondrial adaptations.
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Affiliation(s)
- Rory P. Cunningham
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, Missouri 65212, USA
- Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA
| | - Mary P. Moore
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, Missouri 65212, USA
- Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA
| | - Ryan J. Dashek
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, Missouri 65212, USA
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA
| | - Grace M. Meers
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, Missouri 65212, USA
- Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA
| | - Vivien Jepkemoi
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, Missouri 65212, USA
| | - Takamune Takahashi
- Division of Nephrology and Hypertension, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
| | | | - Jill A. Kanaley
- Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA
| | - Frank W. Booth
- Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA
- Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA
| | - R. Scott Rector
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, Missouri 65212, USA
- Departments of Medicine-Division of Gastroenterology and Hepatology
- Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA
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26
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Seo JH, Lee Y. Association of physical activity with sarcopenia evaluated based on muscle mass and strength in older adults: 2008-2011 and 2014 - 2018 Korea National Health and Nutrition Examination Surveys. BMC Geriatr 2022; 22:217. [PMID: 35296249 PMCID: PMC8928682 DOI: 10.1186/s12877-022-02900-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 03/04/2022] [Indexed: 01/11/2023] Open
Abstract
Background Adequate physical activity (PA) is essential for preventing sarcopenia in older adults. However, there are insufficient epidemiological data on the intensity of PA needed to prevent age-related sarcopenia. The purpose of this study was to investigate the association of PA intensity with skeletal muscle mass and muscle strength. Methods This was a population-based study with a cross-sectional design that was conducted using data from the 2008 − 2011 and 2014 − 2018 Korea National Health and Nutrition Examination Surveys, which included a total of 11,162 participants aged ≥ 60 years. PA was assessed using the results of a questionnaire and organized by intensity, frequency, and duration. The study population was divided into the following groups based on PA intensity: no exercise, walking only, moderate PA, and vigorous PA. To assess sarcopenia, skeletal muscle index (SMI) and hand grip strength (HGS) were measured as indicators of muscle mass and strength, respectively. Logistic regression analysis was used to explore the relationship between PA intensity and sarcopenia. Results SMI and HGS were significantly higher in men and women engaged in moderate to vigorous PA than in those who did not exercise. The odds ratios (ORs) for sarcopenia defined based on SMI and HGS were lowest in men engaged in vigorous PA (0.444, 95% confidence interval [CI]: 0.242 − 0.818 and 0.450, 95% CI: 0.228 − 0.890, respectively). In women, the OR for sarcopenia defined based on HGS was the lowest in the group engaged in vigorous PA (0.441, 95% CI: 0.199 − 0.975), while there was no risk reduction for sarcopenia defined based on SMI. Conclusions Moderate to vigorous PA was highly correlated with SMI and HGS in men and women. Intensive PA was positively correlated with sarcopenia prevention, which can be monitored using HGS.
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Affiliation(s)
- Je Hyun Seo
- Veterans Health Service Medical Center, Veterans Medical Research Institute, Jinhwangdo-ro 61-gil 53, Gangdong-gu Seoul, Korea.
| | - Young Lee
- Veterans Health Service Medical Center, Veterans Medical Research Institute, Jinhwangdo-ro 61-gil 53, Gangdong-gu Seoul, Korea
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27
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Stevanović-Silva J, Beleza J, Coxito P, Costa RC, Ascensão A, Magalhães J. Fit mothers for a healthy future: Breaking the intergenerational cycle of non-alcoholic fatty liver disease with maternal exercise. Eur J Clin Invest 2022; 52:e13596. [PMID: 34120338 DOI: 10.1111/eci.13596] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/01/2021] [Accepted: 05/06/2021] [Indexed: 12/20/2022]
Abstract
UNLABELLED SPECIAL ISSUE: 'FOIEGRAS-Bioenergetic Remodelling in the Pathophysiology and Treatment of Non-Alcoholic Fatty Liver Disease'. BACKGROUND Non-alcoholic fatty liver disease (NAFLD) emerges as significant health burden worldwide. Lifestyle changes, unhealthy dietary habits and physical inactivity, can trigger NAFLD development. Persisting on these habits during pregnancy affects in utero environment and prompts a specific metabolic response in foetus resulting in offspring metabolic maladjustments potentially critical for developing NAFLD later in life. The increasing prevalence of NAFLD, particularly in children, has shifted the research focus towards preventive and therapeutic strategies. Yet, designing effective approaches that can break the NAFLD intergenerational cycle becomes even more complicated. Regular physical exercise (PE) is a powerful non-pharmacological strategy known to counteract deleterious metabolic outcomes. In this narrative review, we aimed to briefly describe NAFLD pathogenesis focusing on maternal nutritional challenge and foetal programming, and to provide potential mechanisms behind the putative intergenerational effect of PE against metabolic diseases, including liver diseases. METHODS Following detailed electronic database search, recent existing evidence about NAFLD development, intergenerational programming and gestational exercise effects was critically analysed and discussed. RESULTS PE during pregnancy could have a great potential to counteract intergenerational transmission of metabolic burden. The interplay between different PE roles-metabolic, endocrine and epigenetic-could offer a more stable in utero environment to the foetus, thus rescuing offspring vulnerability to metabolic disturbances. CONCLUSIONS The better understanding of maternal PE beneficial consequences on offspring metabolism could reinforce the importance of PE during pregnancy as an indispensable strategy in improving offspring health.
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Affiliation(s)
- Jelena Stevanović-Silva
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, Porto, Portugal
| | - Jorge Beleza
- Department of Cell Biology, Physiology & Immunology, Faculty of Biology, University of Barcelona, Barcelona, Spain
| | - Pedro Coxito
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, Porto, Portugal
| | - Rui Carlos Costa
- Department of Communication and Art, Research Institute for Design, Media and Culture (ID+), Aveiro University, Aveiro, Portugal
| | - António Ascensão
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, Porto, Portugal
| | - José Magalhães
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, Porto, Portugal
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28
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So B, Park J, Jang J, Lim W, Imdad S, Kang C. Effect of Aerobic Exercise on Oxidative Stress and Inflammatory Response During Particulate Matter Exposure in Mouse Lungs. Front Physiol 2022; 12:773539. [PMID: 35185596 PMCID: PMC8850364 DOI: 10.3389/fphys.2021.773539] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 12/03/2021] [Indexed: 11/22/2022] Open
Abstract
Regular exercise provides several health benefits that can improve the cardiovascular and musculoskeletal systems, but clear evidence on the effect of exercise-induced hyperventilation in particulate matter (PM) exposure is still lacking. This study aimed to investigate the effects of exercise in PM exposure on reactive oxygen species (ROS) generation, inflammatory response, and mitochondrial integrity in human lung epithelial cells (A549), as well as in mouse lung tissue. In in vitro experiments, PM treatment was shown to significantly increased ROS production, and reduced cell viability and mitochondrial function in A549 cells. The mice were divided into four groups for an in vivo exercise experiment: control (CON), PM inhalation (PI), PM inhalation during exercise (PIE), and exercise (EX) groups. The PI and PIE groups were exposed to 100 μg/m3 of PM for 1 h per day for a week. The PIE and EX groups performed treadmill exercises every day for 1 h at 20 m/min for a week. The levels of pro-inflammatory markers (IL-6 and TNF-α) were significantly higher in the PI group than in the CON group (P < 0.001 and P < 0.01, respectively). The carbonyl protein level was decreased in EX vs. PI (P < 0.001). Mitochondrial fission (Drp1) content was significantly decreased in the EX vs. CON group (P < 0.01), but anti-mitochondrial fission (P-Drp1 Ser637) was increased in the EX vs. PI group (P < 0.05). Mitochondrial autophagy (mitophagy), which is an assessment of mitochondrial integrity, was markedly increased in PI vs. CON (P < 0.001), but the level was reversed in PIE (P < 0.05). Lung fibrosis was increased in PI vs. CON group (P < 0.001), however, the cells were rescued in the PIE (P < 0.001). The number of apoptotic cells was remarkably increased in the PI vs. CON group (P < 0.001), whereas the level was decreased in the PIE (P < 0.001). Taken together, these results showed that short-term exposure to PM triggers oxidative stress, pro-inflammatory responses, and apoptosis in the lungs, but the PM-induced adverse effects on the lung tissue are not exacerbated by exercise-induced PM hyperventilation but rather has a protective effect.
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Affiliation(s)
- Byunghun So
- Molecular Metabolism in Health and Disease, Exercise Physiology Laboratory, Inha University, Incheon, South Korea
| | - Jinhan Park
- Molecular Metabolism in Health and Disease, Exercise Physiology Laboratory, Inha University, Incheon, South Korea
| | - Junho Jang
- Molecular Metabolism in Health and Disease, Exercise Physiology Laboratory, Inha University, Incheon, South Korea
| | - Wonchung Lim
- Department of Sports Medicine, College of Health Science, Cheongju University, Cheongju, South Korea
| | - Saba Imdad
- Molecular Metabolism in Health and Disease, Exercise Physiology Laboratory, Inha University, Incheon, South Korea
- Department of Biomedical Laboratory Science, College of Health Science, Cheongju University, Cheongju, South Korea
| | - Chounghun Kang
- Molecular Metabolism in Health and Disease, Exercise Physiology Laboratory, Inha University, Incheon, South Korea
- Department of Physical Education, College of Education, Inha University, Incheon, South Korea
- *Correspondence: Chounghun Kang,
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29
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Jin SW, Lee GH, Kim JY, Kim CY, Choo YM, Cho W, Han EH, Hwang YP, Kim YA, Jeong HG. Effect of Porcine Whole Blood Protein Hydrolysate on Slow-Twitch Muscle Fiber Expression and Mitochondrial Biogenesis via the AMPK/SIRT1 Pathway. Int J Mol Sci 2022; 23:ijms23031229. [PMID: 35163153 PMCID: PMC8835758 DOI: 10.3390/ijms23031229] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/17/2022] [Accepted: 01/20/2022] [Indexed: 12/11/2022] Open
Abstract
Skeletal muscle is a heterogeneous tissue composed of a variety of functionally different fiber types. Slow-twitch type I muscle fibers are rich with mitochondria, and mitochondrial biogenesis promotes a shift towards more slow fibers. Leucine, a branched-chain amino acid (BCAA), regulates slow-twitch muscle fiber expression and mitochondrial function. The BCAA content is increased in porcine whole-blood protein hydrolysates (PWBPH) but the effect of PWBPH on muscle fiber type conversion is unknown. Supplementation with PWBPH (250 and 500 mg/kg for 5 weeks) increased time to exhaustion in the forced swimming test and the mass of the quadriceps femoris muscle but decreased the levels of blood markers of exercise-induced fatigue. PWBPH also promoted fast-twitch to slow-twitch muscle fiber conversion, elevated the levels of mitochondrial biogenesis markers (SIRT1, p-AMPK, PGC-1α, NRF1 and TFAM) and increased succinate dehydrogenase and malate dehydrogenase activities in ICR mice. Similarly, PWBPH induced markers of slow-twitch muscle fibers and mitochondrial biogenesis in C2C12 myotubes. Moreover, AMPK and SIRT1 inhibition blocked the PWBPH-induced muscle fiber type conversion in C2C12 myotubes. These results indicate that PWBPH enhances exercise performance by promoting slow-twitch muscle fiber expression and mitochondrial function via the AMPK/SIRT1 signaling pathway.
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Affiliation(s)
- Sun Woo Jin
- Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 34134, Korea; (S.W.J.); (G.H.L.); (J.Y.K.); (C.Y.K.); (Y.A.K.)
- Department of R&D, Jinju Bioindustry Foundation, Jinju 52839, Korea;
| | - Gi Ho Lee
- Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 34134, Korea; (S.W.J.); (G.H.L.); (J.Y.K.); (C.Y.K.); (Y.A.K.)
| | - Ji Yeon Kim
- Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 34134, Korea; (S.W.J.); (G.H.L.); (J.Y.K.); (C.Y.K.); (Y.A.K.)
| | - Chae Yeon Kim
- Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 34134, Korea; (S.W.J.); (G.H.L.); (J.Y.K.); (C.Y.K.); (Y.A.K.)
| | - Young Moo Choo
- Department of R&D, Jinju Bioindustry Foundation, Jinju 52839, Korea;
| | - Whajung Cho
- R&D Institute, AMINOLAB Co., Ltd., Seoul 06774, Korea;
| | - Eun Hee Han
- Drug & Disease Target Research Team, Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI), Cheongju 28119, Korea;
| | | | - Yong An Kim
- Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 34134, Korea; (S.W.J.); (G.H.L.); (J.Y.K.); (C.Y.K.); (Y.A.K.)
| | - Hye Gwang Jeong
- Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 34134, Korea; (S.W.J.); (G.H.L.); (J.Y.K.); (C.Y.K.); (Y.A.K.)
- Correspondence: ; Tel.: +82-42-821-5936
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Bassi-Dibai D, Santos-de-Araújo AD, Dibai-Filho AV, de Azevedo LFS, Goulart CDL, Luz GCP, Burke PR, Garcia-Araújo AS, Borghi-Silva A. Rehabilitation of Individuals With Diabetes Mellitus: Focus on Diabetic Myopathy. Front Endocrinol (Lausanne) 2022; 13:869921. [PMID: 35498435 PMCID: PMC9047902 DOI: 10.3389/fendo.2022.869921] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 03/21/2022] [Indexed: 12/20/2022] Open
Abstract
Diabetes mellitus (DM) is a chronic metabolic disease characterized by high blood glucose levels, causing serious damage to the cardiovascular, respiratory, renal and other systems. The prevalence of type 2 diabetes mellitus (T2DM) was 6.28% in 2017, considering all age groups worldwide (prevalence rate of 6,059 cases per 100,000), and its global prevalence is projected to increase to 7,079 cases per 100,000 by 2030. Furthermore, these individuals are often affected by diabetic myopathy, which is the failure to preserve muscle mass and function in the course of DM. This happens in type 1 diabetes mellitus (T1DM) and T2DM. As skeletal muscle plays a key role in locomotion and glucose homeostasis, diabetic myopathy may contribute to additional complications of the disease. In addition, chronic hyperglycemia is associated with lung functional changes seen in patients with DM, such as reduced lung volumes and compliance, inspiratory muscle strength, and lung elastic recoil. Thus, the weakness of the inspiratory muscles, a consequence of diabetic myopathy, can influence exercise tolerance. Thus, moderate strength training in T2DM can contribute to the gain of peripheral muscle strength. Although the literature is robust on the loss of mass and consequent muscle weakness in diabetic myopathy, triggering pathophysiological factors, the impact on functional capacity, as well as the prescription of physical exercise for this condition deserves to be further explored. This review aims to explore the consequences of diabetic myopathy and its implication in rehabilitation from prescription to safety in the practice of physical exercises for these individuals.
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Affiliation(s)
| | | | | | | | - Cássia da Luz Goulart
- Postgraduate Program in Physical Therapy, Universidade Federal de São Carlos, São Carlos, Brazil
| | | | | | | | - Audrey Borghi-Silva
- Postgraduate Program in Physical Therapy, Universidade Federal de São Carlos, São Carlos, Brazil
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31
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Rosa-Caldwell ME, Lim S, Haynie WS, Brown JL, Lee DE, Dunlap KR, Jansen LT, Washington TA, Wiggs MP, Greene NP. Mitochondrial aberrations during the progression of disuse atrophy differentially affect male and female mice. J Cachexia Sarcopenia Muscle 2021; 12:2056-2068. [PMID: 34585846 PMCID: PMC8718086 DOI: 10.1002/jcsm.12809] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 07/27/2021] [Accepted: 08/23/2021] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Disuse decreases muscle size and is predictive of mortality across multiple pathologies. Detriments to mitochondrial function are hypothesized to underlie disuse-induced muscle atrophy. Little data exist on early mechanisms contributing to onset of these pathologies, nor is it known how they differ between sexes. The purpose of this study was to examine differential and conserved responses to mitochondrial quality control in male and female mice during the development and progression of disuse-induced atrophy. METHODS One hundred C57BL/6J mice (50 male and 50 female) were hindlimb unloaded to induce disuse atrophy for 0 (con), 24, 48, 72, or 168 h. At designated time-points, extensor digitorum longus, gastrocnemius, and soleus muscles were collected for analysis of mitochondrial quality control markers. RESULTS One hundred sixty-eight hours of disuse resulted in ~25% lower oxidative muscle fibre CSA in both male (P = 0.003) and female (P = 0.02) mice without any differences due to disuse in glycolytic fibres. In male mice, 48 h of unloading was sufficient to result in ~67% greater mitochondrial oxidative stress as assessed by the reporter gene pMitoTimer compared with 0 h (P = 0.002), this mitochondrial stress preceded detectable muscle loss. However in female mice, mitochondrial oxidative stress did not occur until 168 h of disuse (~40% greater mitochondrial oxidative stress in 168 h compared with 0 h of disuse, P < 0.0001). Blunted oxidative stress in female mice appeared to coincide with greater inductions of autophagy and mitophagy in female mice (~3-fold greater BNIP3 and ~6-fold greater LC3II/I ratio P < 0.0001 and P = 0.038 respectively). Male mice overall had greater reactive oxygen species (ROS) production compared with female mice. Female mice had a greater induction of ROS within 24 h of disuse (~4-fold greater compared with 0 h, P < 0.0001); whereas male mice did not have greater ROS production until 168 h of disuse (~2-fold greater, P < 0.0001). Although all muscle types exhibited some alterations to mitochondrial quality control, such as increased markers of mitophagy and fission, the soleus muscle in both male and female mice exhibited consistent alterations to various markers of mitochondrial quality. Markers of mitochondrial translation were approximately 30-50% lower within 24 h of unloading in both male and female soleus muscle (P value ranges: <0.0001-0.03). CONCLUSIONS Disuse negatively affects mitochondria differentially between sexes during development of muscle wasting. Acutely, female mice may forgo muscle mass to maintain mitochondrial quality compared with male mice. These differences may contribute to divergent clinical manifestations of atrophy.
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Affiliation(s)
- Megan E Rosa-Caldwell
- Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA
| | - Seongkyun Lim
- Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA
| | - Wesley S Haynie
- Exercise Muscle Biology Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA
| | - Jacob L Brown
- Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA
| | - David E Lee
- Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA
| | - Kirsten R Dunlap
- Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA
| | - Lisa T Jansen
- Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA
| | - Tyrone A Washington
- Exercise Muscle Biology Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA
| | - Michael P Wiggs
- Department of Health, Human Performance and Recreation, Baylor University, Waco, TX, USA
| | - Nicholas P Greene
- Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA
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32
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Candidate Genes of Regulation of Skeletal Muscle Energy Metabolism in Athletes. Genes (Basel) 2021; 12:genes12111682. [PMID: 34828287 PMCID: PMC8625318 DOI: 10.3390/genes12111682] [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: 09/24/2021] [Revised: 10/13/2021] [Accepted: 10/22/2021] [Indexed: 01/20/2023] Open
Abstract
All biological processes associated with high sports performance, including energy metabolism, are influenced by genetics. DNA sequence variations in such genes, single nucleotide variants (SNVs), could confer genetic advantages that can be exploited to achieve optimal athletic performance. Ignorance of these features can create genetic “barriers” that prevent professional athletes from pursuing a career in sports. Predictive Genomic DNA Profiling reveals single nucleotide variations (SNV) that may be associated with better suitability for endurance, strength and speed sports. (1) Background: To conduct a research on candidate genes associated with regulation of skeletal muscle energy metabolism among athletes. (2) Methods: We have searched for articles in SCOPUS, Web of Science, Google Scholar, Clinical keys, PubMed, e-LIBRARY databases for the period of 2010–2020 using keywords and keywords combinations; (4) Conclusions: Identification of genetic markers associated with the regulation of energy metabolism in skeletal muscles can help sports physicians and coaches develop personalized strategies for selecting children, teenagers and young adults for endurance, strength and speed sports (such as jogging, middle or long distance runs). However, the multifactorial aspect of sport performances, including impact of genetics, epigenetics, environment (training and etc.), is important for personalized strategies for selecting of athletes. This approach could improve sports performance and reduce the risk of sports injuries to the musculoskeletal system.
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33
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Roberts FL, Markby GR. New Insights into Molecular Mechanisms Mediating Adaptation to Exercise; A Review Focusing on Mitochondrial Biogenesis, Mitochondrial Function, Mitophagy and Autophagy. Cells 2021; 10:cells10102639. [PMID: 34685618 PMCID: PMC8533934 DOI: 10.3390/cells10102639] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 09/27/2021] [Accepted: 09/29/2021] [Indexed: 12/25/2022] Open
Abstract
Exercise itself is fundamental for good health, and when practiced regularly confers a myriad of metabolic benefits in a range of tissues. These benefits are mediated by a range of adaptive responses in a coordinated, multi-organ manner. The continued understanding of the molecular mechanisms of action which confer beneficial effects of exercise on the body will identify more specific pathways which can be manipulated by therapeutic intervention in order to prevent or treat various metabolism-associated diseases. This is particularly important as exercise is not an available option to all and so novel methods must be identified to confer the beneficial effects of exercise in a therapeutic manner. This review will focus on key emerging molecular mechanisms of mitochondrial biogenesis, autophagy and mitophagy in selected, highly metabolic tissues, describing their regulation and contribution to beneficial adaptations to exercise.
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Soliman AM, Das S, Mahakkanukrauh P. Inflammatory Molecular Mediators and Pathways Involved in Vascular Aging and Stroke: A Comprehensive Review. Curr Med Chem 2021; 29:5522-5542. [PMID: 34488579 DOI: 10.2174/0929867328666210901122359] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 07/01/2021] [Accepted: 07/23/2021] [Indexed: 11/22/2022]
Abstract
There is an increase in the incidence of cardiovascular diseases with aging and it is one of the leading causes of death worldwide. The main cardiovascular pathologies include atherosclerosis, stroke, myocardial infarction, hypertension and stroke. Chronic inflammation is one of the significant contributors to the age-related vascular diseases. Therefore, it is important to understand the molecular mechanisms of the persistent inflammatory conditions occurring in the blood vessels as well as the signaling pathways involved. Herein, we performed an extant search of literature involving PubMed, ISI, WoS and Scopus databases for retrieving all relevant articles with the most recent findings illustrating the potential role of various inflammatory mediators along with their proposed activated pathways in the pathogenesis and progression of vascular aging. We also highlight the major pathways contributing to age-related vascular disorders. The outlined molecular mechanisms, pathways and mediators of vascular aging represent potential drug targets that can be utilized to inhibit and/or slow the pathogenesis and progression of vascular aging.
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Affiliation(s)
- Amro M Soliman
- Department of Biological Sciences-Physiology, Cell and Developmental Biology, University of Alberta, Edmonton, AB T6G 2R3. Canada
| | - Srijit Das
- Department of Human & Clinical Anatomy, College of Medicine & Health Sciences, Sultan Qaboos University, P.C. 123, Al Khoud, Muscat. Oman
| | - Pasuk Mahakkanukrauh
- Department of Anatomy & Excellence center of Osteology Research and Training, Cadaveric Surgical and Training Center, Chiang Mai University, Chiang Mai 50200. Thailand
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35
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Koh FH, Chua JMW, Tan JLJ, Foo FJ, Tan WJ, Sivarajah SS, Ho LML, Teh BT, Chew MH. Paradigm shift in gastrointestinal surgery − combating sarcopenia with prehabilitation: Multimodal review of clinical and scientific data. World J Gastrointest Surg 2021; 13:734-755. [PMID: 34512898 PMCID: PMC8394378 DOI: 10.4240/wjgs.v13.i8.734] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/08/2021] [Accepted: 07/12/2021] [Indexed: 02/06/2023] Open
Abstract
A growing body of evidence has demonstrated the prognostic significance of sarcopenia in surgical patients as an independent predictor of postoperative complications and outcomes. These included an increased risk of total complications, major complications, re-admissions, infections, severe infections, 30 d mortality, longer hospital stay and increased hospitalization expenditures. A program to enhance recovery after surgery was meant to address these complications; however, compliance to the program since its introduction has been less than ideal. Over the last decade, the concept of prehabilitation, or “pre-surgery rehabilitation”, has been discussed. The presurgical period represents a window of opportunity to boost and optimize the health of an individual, providing a compensatory “buffer” for the imminent reduction in physiological reserve post-surgery. Initial results have been promising. We review the literature to critically review the utility of prehabilitation, not just in the clinical realm, but also in the scientific realm, with a resource management point-of-view.
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Affiliation(s)
- Frederick H Koh
- Division of Surgery, Sengkang General Hospital, Singapore 544886, Singapore
| | - Jason MW Chua
- Institute of Molecular and Cell Biology, Agency for Science Technology and Research, Singapore 138673, Singapore
| | - Joselyn LJ Tan
- Institute of Molecular and Cell Biology, Agency for Science Technology and Research, Singapore 138673, Singapore
| | - Fung-Joon Foo
- Division of Surgery, Sengkang General Hospital, Singapore 544886, Singapore
| | - Winson J Tan
- Division of Surgery, Sengkang General Hospital, Singapore 544886, Singapore
| | | | - Leonard Ming Li Ho
- Division of Surgery, Sengkang General Hospital, Singapore 544886, Singapore
| | - Bin-Tean Teh
- Duke-NUS Graduate Medical School, National Cancer Centre Singapore, Singapore 169610, Singapore
| | - Min-Hoe Chew
- Division of Surgery, Sengkang General Hospital, Singapore 544886, Singapore
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36
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Huwatibieke B, Yin W, Liu L, Jin Y, Xiang X, Han J, Zhang W, Li Y. Mammalian Target of Rapamycin Signaling Pathway Regulates Mitochondrial Quality Control of Brown Adipocytes in Mice. Front Physiol 2021; 12:638352. [PMID: 34335285 PMCID: PMC8317026 DOI: 10.3389/fphys.2021.638352] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 05/26/2021] [Indexed: 01/13/2023] Open
Abstract
The mammalian target of rapamycin (mTOR) is an important protein kinase that senses changes in extracellular and intracellular energy levels and plays a key role in regulating energy metabolism. Brown adipose tissue, which can be converted to white adipose tissue, contains a large number of mitochondria and regulates energy expenditure through thermogenesis. Because obesity is a process of fat accumulation due to chronic excessive energy intake, we attempted to determine whether the mTOR signaling pathway can affect the mitochondrial quality control of brown adipocytes through sensing energy status, thereby regulating brown/white adipocyte transformation. In the present study, through activation or inhibition of mTOR signaling, we detected mitochondrial biogenesis, dynamics, and autophagy-related markers in brown adipocytes. We found that activation of mTOR signaling downregulated the expression of mitochondrial biogenesis, dynamics, and autophagy-relevant markers and inhibited the mitochondrial quality control of brown adipocytes, indicating a phenotypic transformation of brown to white adipocytes. In contrast, inhibition of mTOR signaling upregulated the expression of mitochondrial biogenesis, dynamics, and mitophagy-relevant markers and strengthened mitochondrial quality control, suggesting an inhibition of the phenotypic transformation of brown to white adipocytes. In conclusion, the mTOR signaling pathway plays an important role in modulating the transformation of adipocytes by regulating mitochondrial quality control.
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Affiliation(s)
- Bahetiyaer Huwatibieke
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China
| | - Wenzhen Yin
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China
| | - Lingchao Liu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China
| | - Yuxin Jin
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China.,Department of Integration of Chinese and Western Medicine, Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
| | - Xinxin Xiang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China.,Department of Pathology, Central Hospital of Zibo, Zibo, China
| | - Jingyan Han
- Department of Integration of Chinese and Western Medicine, Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
| | - Weizhen Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China
| | - Yin Li
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China.,Department of Integration of Chinese and Western Medicine, Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
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37
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Liu S, Yu C, Xie L, Niu Y, Fu L. Aerobic Exercise Improves Mitochondrial Function in Sarcopenia Mice Through Sestrin2 in an AMPKα2-Dependent Manner. J Gerontol A Biol Sci Med Sci 2021; 76:1161-1168. [PMID: 33512470 DOI: 10.1093/gerona/glab029] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Indexed: 12/22/2022] Open
Abstract
Sarcopenia, the age-related loss of skeletal muscle mass and function, contributes to high morbidity and mortality in the older population. Regular exercise is necessary to avoid the initiation and progression of sarcopenia, in which the underlying molecular mechanism is still not clear. Our data revealed that the outcomes induced by sarcopenia, including muscle mass and strength loss, decreased cross-sectional area of gastrocnemius fiber, chronic inflammation, and increased dysfunctional mitochondria, were reversed by regulation exercise. Knockout or silencing of Sestrin2 (Sesn2) resulted in imbalanced mitochondrial fusion and fission, mitochondrial biogenesis, and mitophagy damage in vivo and in vitro, which was attenuated by aerobic exercise or overexpression of Sesn2. Moreover, we found that the effects of Sesn2 on mitochondrial function are dependent on AMP-activated protein kinase α2 (AMPKα2). This study indicates that aerobic exercise alleviates the negative effects resulting from sarcopenia via the Sesn2/AMPKα2 pathway and provides new insights into the molecular mechanism by which the Sesn2/AMPKα2 signaling axis mediates the beneficial impact of exercise on sarcopenia.
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Affiliation(s)
- Sujuan Liu
- Department of Anatomy and Histology, School of Basic Medical Science, Tianjin Medical University, China
| | - Chunxia Yu
- Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, China
| | - Lingjian Xie
- Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, China
| | - Yanmei Niu
- Department of Rehabilitation, School of Medical Technology, Tianjin Medical University, China
| | - Li Fu
- Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, China.,Department of Rehabilitation, School of Medical Technology, Tianjin Medical University, China
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38
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Dietary Sodium Nitrate Activates Antioxidant and Mitochondrial Dynamics Genes after Moderate Intensity Acute Exercise in Metabolic Syndrome Patients. J Clin Med 2021; 10:jcm10122618. [PMID: 34198661 PMCID: PMC8232343 DOI: 10.3390/jcm10122618] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 06/08/2021] [Accepted: 06/11/2021] [Indexed: 01/14/2023] Open
Abstract
Exercise can induce a pro-inflammatory response in aged subjects with metabolic disorders and nitrate supplementation has shown anti-inflammatory effects. We evaluated the influence of dietary nitrate on the response of the antioxidant and mitochondrial dynamics genes to acute exercise in peripheral blood mononuclear cells (PBMCs), as well as the antioxidant and the inflammatory response of PBMCs against immune stimulation. Metabolic syndrome patients participated in a crossover study in which they consumed a beverage containing 16 mM sodium nitrate or a placebo with the same composition without nitrate before performing a submaximal test at 60–70% of their maximal heart rate for 30 min. The intake of nitrate increased the nitrate plus nitrite plasma levels about 8-fold and induced the upregulation of catalase, superoxide dismutase, glutathione peroxidase, mitofusin 2 and PGC1α in PBMCs after exercise. The gene expression of catalase and TNFα was enhanced by phorbol myristate acetate (PMA) only in the placebo group, while the glutathione peroxidase expression was enhanced by PMA only after nitrate intake. The intake of nitrate by metabolic syndrome patients induces an antioxidant and mitochondrial response to exercise at the same time that it attenuates the pro-inflammatory response to immune stimulation.
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Cardinale DA, Gejl KD, Petersen KG, Nielsen J, Ørtenblad N, Larsen FJ. Short-term intensified training temporarily impairs mitochondrial respiratory capacity in elite endurance athletes. J Appl Physiol (1985) 2021; 131:388-400. [PMID: 34110230 DOI: 10.1152/japplphysiol.00829.2020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
The maintenance of healthy and functional mitochondria is the result of a complex mitochondrial turnover and herein quality-control program that includes both mitochondrial biogenesis and autophagy of mitochondria. The aim of this study was to examine the effect of an intensified training load on skeletal muscle mitochondrial quality control in relation to changes in mitochondrial oxidative capacity, maximal oxygen consumption, and performance in highly trained endurance athletes. Elite endurance athletes (n = 27) performed high-intensity interval exercise followed by moderate-intensity continuous exercise 3 days per week for 4 wk in addition to their usual volume of training. Mitochondrial oxidative capacity, abundance of mitochondrial proteins, markers of autophagy, and antioxidant capacity of skeletal muscle were assessed in skeletal muscle biopsies before and after the intensified training period. The intensified training period increased several autophagy markers suggesting an increased turnover of mitochondrial and cytosolic proteins. In permeabilized muscle fibers, mitochondrial respiration was ∼20% lower after training although some markers of mitochondrial density increased by 5%-50%, indicative of a reduced mitochondrial quality by the intensified training intervention. The antioxidative proteins UCP3, ANT1, and SOD2 were increased after training, whereas we found an inactivation of aconitase. In agreement with the lower aconitase activity, the amount of mitochondrial LON protease that selectively degrades oxidized aconitase was doubled. Together, this suggests that mitochondrial respiratory function is impaired during the initial recovery from a period of intensified endurance training whereas mitochondrial quality control is slightly activated in highly trained skeletal muscle.NEW & NOTEWORTHY We show that mitochondrial respiration is temporarily impaired after a period of intensified exercise training in elite athletes. In parallel, proteins involved in the antioxidative response including SOD2, UCP3, and ANT2 were upregulated, whereas mitochondrial biogenesis was slightly activated. Despite the mitochondrial respiratory impairments, physical performance was improved a few days after the intense training period.
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Affiliation(s)
- Daniele A Cardinale
- Åstrand Laboratory, Department of Physiology, Nutrition, and Biomechanics, The Swedish School of Sport and Health Sciences (GIH), Stockholm, Sweden.,Elite Performance Centre, Bosön-Swedish Sports Confederation, Lidingö, Sweden
| | - Kasper D Gejl
- Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
| | - Kristine G Petersen
- Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
| | - Joachim Nielsen
- Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
| | - Niels Ørtenblad
- Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
| | - Filip J Larsen
- Åstrand Laboratory, Department of Physiology, Nutrition, and Biomechanics, The Swedish School of Sport and Health Sciences (GIH), Stockholm, Sweden
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40
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Complex Exercise Improves Anti-Inflammatory and Anabolic Effects in Osteoarthritis-Induced Sarcopenia in Elderly Women. Healthcare (Basel) 2021; 9:healthcare9060711. [PMID: 34200794 PMCID: PMC8230475 DOI: 10.3390/healthcare9060711] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 06/07/2021] [Accepted: 06/08/2021] [Indexed: 12/27/2022] Open
Abstract
We investigated the effects of a 15-week complex exercise program on osteoarthritis and sarcopenia by analyzing anabolic effects and the impact on the activities of daily living (ADLs). Nineteen women aged ≥60 years with sarcopenia (SEG, n = 9) or diagnosed with osteoarthritis with sarcopenia (OSEG, n = 10) were enrolled and underwent an exercise program. Insulin-like growth factor 1 (IGF-1), irisin, myostatin, interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-a) levels were analyzed pre- and post-intervention. Thigh cross-sectional area (TCSA) was measured pre- and post-intervention via computed tomography. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Short Physical Performance Battery (SPBB) were assessed pre- and post-interventions to assess ADL. There was a significant interaction effect between SEG and OSEG at the IGF-1 level post-intervention. Irisin increased and myostatin decreased post-intervention in both groups. IL-10 increased and TNF-α decreased post-intervention with a significant interaction effect in the OSEG group. TCSAs increased post-intervention in both groups. There was a significant interaction between the two groups. OSEG showed a greater WOMAC decrease and SPPB increase post-intervention, and there was a significant interaction effect. Combined exercise may be effective in improving biochemical factors, anabolic effects, and ADL in elderly women with osteoarthritis and sarcopenia.
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Vanderveen BN, Fix DK, Counts BR, Carson JA. The Effect of Wheel Exercise on Functional Indices of Cachexia in Tumor-bearing Mice. Med Sci Sports Exerc 2021; 52:2320-2330. [PMID: 33064407 DOI: 10.1249/mss.0000000000002393] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Cancer-related fatigue and muscle wasting have received significant attention over the last few decades with the goal of establishing interventions that can improve cancer patient life quality and survival. Increased physical activity has shown to reduce cancer-associated fatigue and has been proposed as a promising therapeutic to attenuate cancer-induced wasting. However, significant gaps remain in our understanding of how physical activity affects the compositional and functional changes that initiate muscle wasting. The purpose of the current study was to determine the effect of wheel exercise on body composition and functional indices of cancer cachexia before the development of significant wasting. METHODS Thirteen-week-old male Apc (MIN) and C57BL/6 (B6) mice were given free wheel access (W) or a locked wheel (Sed) for 5 wk. RESULTS Wheel activity was reduced in the MIN compared with B6; however, wheel access increased complex II expression in isolated skeletal muscle mitochondria regardless of genotype. Wheel access had no effect on tumor burden or plasma interleukin-6 in the MIN. MIN-W increased body weight and lean mass compared with MIN-Sed, and there was a direct correlation between wheel distance and lean mass change. MIN-W increased grip strength and treadmill time to fatigue compared with MIN-Sed. Within MIN-W mice, skeletal muscle fatigability was only improved in high runners (>60 min·d). CONCLUSIONS Our results suggest that there were therapeutic benefits of increased activity related to body composition, behavior, and whole-body function that were not dependent on exercise duration; however, there was an exercise threshold needed to improve skeletal muscle fatigability in tumor-bearing mice. Interestingly, wheel access was able to improve compositional and functional outcomes without mitigating tumor number or size.
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Affiliation(s)
| | - Dennis K Fix
- Department of Exercise Science, University of South Carolina, Columbia, SC
| | - Brittany R Counts
- Department of Physical Therapy, College of Health Professions, The University of Tennessee Health Sciences Center, Memphis, TN
| | - James A Carson
- Department of Physical Therapy, College of Health Professions, The University of Tennessee Health Sciences Center, Memphis, TN
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Circulating Mediators of Apoptosis and Inflammation in Aging; Physical Exercise Intervention. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18063165. [PMID: 33808526 PMCID: PMC8003155 DOI: 10.3390/ijerph18063165] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 03/13/2021] [Accepted: 03/17/2021] [Indexed: 12/27/2022]
Abstract
Sarcopenia is an age-related loss of skeletal muscle mass caused by many cellular mechanisms and also by lifestyle factors such as low daily physical activity. In addition, it has been shown that sarcopenia may be associated with inflammation and cognitive impairment in old age. Regular exercise is key in reducing inflammation and preventing sarcopenia and diseases related to cognitive impairment. The study was designed to assess the impact of exercise training on circulating apoptotic and inflammatory markers of sarcopenia in older adults. Eighty older adults aged 70.5 ± 5.8 years were randomized to the physically active group who participated in a 10-month Tai-Chi training session (TC, n = 40) and the control group who participated in health education sessions (HE, n = 40). Tai-Chi training caused a significant decrease in fat mass (FM) by 3.02 ± 3.99%, but an increase in appendicular skeletal muscle mass index (ASMI) by 1.76 ± 3.17% and gait speed by 9.07 ± 11.45%. Tai-Chi training elevated the plasma levels of C-reactive protein (CRP), tumor necrosis factor (TNFα), and tumor necrosis receptor factor II (TNFRII), and decreased caspases 8 and 9. Despite the increase in TNFα, apoptosis was not initiated, i.e., the cell-free DNA level did not change in the TC group. The study demonstrated that Tai-Chi training significantly reduced the symptoms of sarcopenia through the changes in body composition and physical performance, and improvements in cytokine-related mechanisms of apoptosis.
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Skelly LE, Gillen JB, Frankish BP, MacInnis MJ, Godkin FE, Tarnopolsky MA, Murphy RM, Gibala MJ. Human skeletal muscle fiber type-specific responses to sprint interval and moderate-intensity continuous exercise: acute and training-induced changes. J Appl Physiol (1985) 2021; 130:1001-1014. [PMID: 33630680 DOI: 10.1152/japplphysiol.00862.2020] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
There are limited and equivocal data regarding potential fiber type-specific differences in the human skeletal muscle response to sprint interval training (SIT), including how this compares with moderate-intensity continuous training (MICT). We examined mixed-muscle and fiber type-specific responses to a single session (study 1) and to 12 wk (study 2) of MICT and SIT using Western blot analysis. MICT consisted of 45 min of cycling at ∼70% of maximal heart rate, and SIT involved 3 × 20-s "all-out" sprints interspersed with 2 min of recovery. Changes in signaling proteins involved in mitochondrial biogenesis in mixed-muscle and pooled fiber samples were similar after acute MICT and SIT. This included increases in the ratios of phosphorylated to total acetyl-CoA carboxylase and p38 mitogen-activated protein kinase protein content (main effects, P < 0.05). Following training, mitochondrial content markers including the protein content of cytochrome c oxidase subunit IV and NADH:ubiquinone oxidoreductase subunit A9 were increased similarly in mixed-muscle and type IIa fibers (main effects, P < 0.05). In contrast, only MICT increased these markers of mitochondrial content in type I fibers (interactions, P < 0.05). MICT and SIT also similarly increased the content of mitochondrial fusion proteins optic atrophy 1 (OPA1) and mitofusin 2 in mixed-muscle, and OPA1 in pooled fiber samples (main effects, P < 0.02). In summary, acute MICT and SIT elicited similar fiber type-specific responses of signaling proteins involved in mitochondrial biogenesis, whereas 12 wk of training revealed differential responses of mitochondrial content markers in type I but not type IIa fibers.NEW & NOTEWORTHY We examined mixed-muscle and fiber type-specific responses to a single session and to 12 wk of moderate-intensity continuous training (MICT) and sprint interval training (SIT) in humans. Both interventions elicited generally similar responses, although the training-induced increases in type I fiber-specific markers of mitochondrial content were greater in MICT than in SIT. These findings advance our understanding of the potential role of fiber type-specific changes in determining the human skeletal muscle response to intermittent and continuous exercise.
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Affiliation(s)
- Lauren E Skelly
- Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada
| | - Jenna B Gillen
- Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.,Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Ontario, Canada
| | - Barnaby P Frankish
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Victoria, Australia
| | - Martin J MacInnis
- Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.,Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
| | - F Elizabeth Godkin
- Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada
| | - Mark A Tarnopolsky
- Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.,Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
| | - Robyn M Murphy
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Melbourne, Victoria, Australia.,Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, Victoria, Australia
| | - Martin J Gibala
- Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada
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Quezada ER, Díaz-Vegas A, Jaimovich E, Casas M. Changes in Gene Expression of the MCU Complex Are Induced by Electrical Stimulation in Adult Skeletal Muscle. Front Physiol 2021; 11:601313. [PMID: 33574764 PMCID: PMC7870689 DOI: 10.3389/fphys.2020.601313] [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: 08/31/2020] [Accepted: 11/27/2020] [Indexed: 11/29/2022] Open
Abstract
The slow calcium transient triggered by low-frequency electrical stimulation (ES) in adult muscle fibers and regulated by the extracellular ATP/IP3/IP3R pathway has been related to muscle plasticity. A regulation of muscular tropism associated with the MCU has also been described. However, the role of transient cytosolic calcium signals and signaling pathways related to muscle plasticity over the regulation of gene expression of the MCU complex (MCU, MICU1, MICU2, and EMRE) in adult skeletal muscle is completely unknown. In the present work, we show that 270 0.3-ms-long pulses at 20-Hz ES (and not at 90 Hz) transiently decreased the mRNA levels of the MCU complex in mice flexor digitorum brevis isolated muscle fibers. Importantly, when ATP released after 20-Hz ES is hydrolyzed by the enzyme apyrase, the repressor effect of 20 Hz on mRNA levels of the MCU complex is lost. Accordingly, the exposure of muscle fibers to 30 μM exogenous ATP produces the same effect as 20-Hz ES. Moreover, the use of apyrase in resting conditions (without ES) increased mRNA levels of MCU, pointing out the importance of extracellular ATP concentration over MCU mRNA levels. The use of xestospongin B (inhibitor of IP3 receptors) also prevented the decrease of mRNA levels of MCU, MICU1, MICU2, and EMRE mediated by a low-frequency ES. Our results show that the MCU complex can be regulated by electrical stimuli in a frequency-dependent manner. The changes observed in mRNA levels may be related to changes in the mitochondria, associated with the phenotypic transition from a fast- to a slow-type muscle, according to the described effect of this stimulation frequency on muscle phenotype. The decrease in mRNA levels of the MCU complex by exogenous ATP and the increase in MCU levels when basal ATP is reduced with the enzyme apyrase indicate that extracellular ATP may be a regulator of the MCU complex. Moreover, our results suggest that this regulation is part of the axes linking low-frequency stimulation with ATP/IP3/IP3R.
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Affiliation(s)
- Esteban R Quezada
- Center for Exercise, Metabolism, and Cancer, Physiology and Biophysics Program, Biomedical Sciences Institute (ICBM), Faculty of Medicine, University of Chile, Santiago, Chile
| | - Alexis Díaz-Vegas
- Center for Exercise, Metabolism, and Cancer, Physiology and Biophysics Program, Biomedical Sciences Institute (ICBM), Faculty of Medicine, University of Chile, Santiago, Chile
| | - Enrique Jaimovich
- Center for Exercise, Metabolism, and Cancer, Physiology and Biophysics Program, Biomedical Sciences Institute (ICBM), Faculty of Medicine, University of Chile, Santiago, Chile
| | - Mariana Casas
- Center for Exercise, Metabolism, and Cancer, Physiology and Biophysics Program, Biomedical Sciences Institute (ICBM), Faculty of Medicine, University of Chile, Santiago, Chile
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Chang WT, Huang SC, Cheng HL, Chen SC, Hsu CL. Rutin and Gallic Acid Regulates Mitochondrial Functions via the SIRT1 Pathway in C2C12 Myotubes. Antioxidants (Basel) 2021; 10:antiox10020286. [PMID: 33668647 PMCID: PMC7918168 DOI: 10.3390/antiox10020286] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 02/10/2021] [Accepted: 02/10/2021] [Indexed: 11/16/2022] Open
Abstract
Mitochondria are highly dynamic organelles, balancing synthesis and degradation in response to increases in mitochondrial turnover (i.e., biogenesis, fusion, fission, and mitophagy) and function. The aim of this study was to investigate the role of polyphenols in the regulation of mitochondrial functions and dynamics in C2C12 myotubes and their molecular mechanisms. Our results indicate that gallic acid and rutin are the most potential polyphenol compounds in response to 15 phenolic acids and 5 flavonoids. Gallic acid and rutin were associated with a significantly greater mitochondrial DNA (cytochrome b and COX-II), mitochondrial enzymatic activities (including citrate synthase and cytochrome c oxidase), and intracellular ATP levels in C2C12 myotubes. Moreover, gallic acid and rutin significantly increased the gene expressions of mitochondrial turnover in C2C12 myotubes. Our findings indicated that gallic acid and rutin may have a beneficial effect on mitochondrial dynamics via regulation of the SIRT1-associated pathway in C2C12 myotubes.
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Affiliation(s)
- Wei-Tang Chang
- Department of Nutrition and Health Nutrition, Chinese Culture University, Taipei 11114, Taiwan;
| | - Shih-Chien Huang
- Department of Nutrition, Chung Shan Medical University, Taichung 40201, Taiwan; (S.-C.H.); (H.-L.C.)
| | - Hsin-Lin Cheng
- Department of Nutrition, Chung Shan Medical University, Taichung 40201, Taiwan; (S.-C.H.); (H.-L.C.)
| | - Shiuan-Chih Chen
- Institute of Medicine and School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
- Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Chin-Lin Hsu
- Department of Nutrition, Chung Shan Medical University, Taichung 40201, Taiwan; (S.-C.H.); (H.-L.C.)
- Department of Nutrition, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
- Correspondence: ; Tel.: +886-4-2473-0022; Fax: +886-4-2324-8175
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Krekeler BN, Rowe LM, Connor NP. Dose in Exercise-Based Dysphagia Therapies: A Scoping Review. Dysphagia 2021; 36:1-32. [PMID: 32140905 PMCID: PMC7483259 DOI: 10.1007/s00455-020-10104-3] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Accepted: 02/25/2020] [Indexed: 01/05/2023]
Abstract
BACKGROUND Optimal exercise doses for exercise-based approaches to dysphagia treatment are unclear. To address this gap in knowledge, we performed a scoping review to provide a record of doses reported in the literature. A larger goal of this work was to promote detailed consideration of dosing parameters in dysphagia exercise treatments in intervention planning and outcome reporting. METHODS We searched PubMed, Scopus[Embase], CINAHL, and Cochrane databases from inception to July 2019, with search terms relating to dysphagia and exercises to treat swallowing impairments. Of the eligible 1906 peer-reviewed articles, 72 met inclusionary criteria by reporting, at minimum, both the frequency and duration of their exercise-based treatments. RESULTS Study interventions included tongue exercise (n = 16), Shaker/head lift (n = 13), respiratory muscle strength training (n = 6), combination exercise programs (n = 20), mandibular movement exercises (n = 7), lip muscle training (n = 5), and other programs that did not fit into the categories described above (n = 5). Frequency recommendations varied greatly by exercise type. Duration recommendations ranged from 4 weeks to 1 year. In articles reporting repetitions (n = 66), the range was 1 to 120 reps/day. In articles reporting intensity (n = 59), descriptions included values for force, movement duration, or descriptive verbal cues, such as "as hard as possible." Outcome measures were highly varied across and within specific exercise types. CONCLUSIONS We recommend inclusion of at least the frequency, duration, repetition, and intensity components of exercise dose to improve reproducibility, interpretation, and comparison across studies. Further research is required to determine optimal dose ranges for the wide variety of exercise-based dysphagia interventions.
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Affiliation(s)
- Brittany N Krekeler
- Department of Communication Sciences and Disorders, University of Wisconsin-Madison, Goodnight Hall, 1300 University Ave, Madison, WI, 53706, USA.
- Department of Surgery-Otolaryngology, Clinical Science Center, University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI, 53792-7375, USA.
- Department of Communication Sciences and Disorders, Northwestern University, Swallowing Cross-Systems Collaborative, 2240 Campus Drive, Evanston, IL, 60208, USA.
| | - Linda M Rowe
- Department of Communication Sciences and Disorders, University of Wisconsin-Madison, Goodnight Hall, 1300 University Ave, Madison, WI, 53706, USA
- Department of Surgery-Otolaryngology, Clinical Science Center, University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI, 53792-7375, USA
| | - Nadine P Connor
- Department of Communication Sciences and Disorders, University of Wisconsin-Madison, Goodnight Hall, 1300 University Ave, Madison, WI, 53706, USA
- Department of Surgery-Otolaryngology, Clinical Science Center, University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI, 53792-7375, USA
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Liu S, Yang D, Yu L, Aluo Z, Zhang Z, Qi Y, Li Y, Song Z, Xu G, Zhou L. Effects of lycopene on skeletal muscle-fiber type and high-fat diet-induced oxidative stress. J Nutr Biochem 2021; 87:108523. [PMID: 33039582 DOI: 10.1016/j.jnutbio.2020.108523] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 09/26/2020] [Accepted: 10/01/2020] [Indexed: 01/05/2023]
Abstract
Increasing studies report that many natural products can participate in formation of muscle fibers. This study aimed to investigate the effect of lycopene on skeletal muscle-fiber type in vivo and in vitro. C2C12 myoblasts were used in vitro study, and the concentration of lycopene was 10 µM. In vivo, 8-week-old male C57/BL6 mice were used and divided into four groups (n=8): (1) ND: normal-fat diet; (2) ND+Lyc: normal-fat diet mixed with 0.33% w/w lycopene; (3) HFD: high-fat diet; and (4) HFD+Lyc: high-fat diet mixed with 0.33% w/w lycopene. The mice tissue samples were collected after 8 weeks feeding. We found that lycopene supplementation enhanced the protein expression of slow-twitch fiber, succinate dehydrogenase, and malic dehydrogenase enzyme activities, whereas lycopene reduced the protein expression of fast-twitch fibers, lactate dehydrogenase, pyruvate kinase enzyme activities. Moreover, lycopene can promote skeletal muscle triglyceride deposition, enhanced the mRNA expression of genes related to lipid synthesis, reduced the mRNA expression of genes related to lipolysis. And high-fat diet-induced dyslipidemia and oxidative stress were attenuated after lycopene supplementation. Additionally, lycopene supplementation reduced the glycolytic reserve but enhanced mitochondrial ATP production in C2C12 cells. These results demonstrated that lycopene affects the activities of metabolic enzymes in muscle fibers, promotes the expression of slow-twitch fibers, and enhanced mitochondrial respiratory capacity. We speculated that lycopene affects the muscle-fiber type through aerobic oxidation, suggesting that lycopene exerts potential beneficial effects on skeletal muscle metabolism.
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Affiliation(s)
- Siqi Liu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning, PR China
| | - Dan Yang
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning, PR China
| | - Lin Yu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning, PR China
| | - Zhier Aluo
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning, PR China
| | - Zhiwang Zhang
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning, PR China
| | - Yilin Qi
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning, PR China
| | - Yixing Li
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning, PR China
| | - Ziyi Song
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning, PR China
| | - Gaoxiao Xu
- Teaching and Research Section of Biotechnology, Nanning University, Nanning, PR China.
| | - Lei Zhou
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning, PR China.
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Vettori A, Paolacci S, Maltese PE, Herbst KL, Cestari M, Michelini S, Michelini S, Samaja M, Bertelli M. Genetic Determinants of the Effects of Training on Muscle and Adipose Tissue Homeostasis in Obesity Associated with Lymphedema. Lymphat Res Biol 2020; 19:322-333. [PMID: 33373545 DOI: 10.1089/lrb.2020.0057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
It is widely accepted that metabolic changes associated with training are influenced by a person's genetic background. In this review, we explore the polymorphisms underlying interindividual variability in response to training of weight loss and muscle mass increase in obese individuals, with or without lymphedema, and in normal-weight subjects. We searched PubMed for articles in English published up to May 2019 using the following keywords: (((physical training[Title/Abstract] OR sport activity[Title/Abstract]) AND predisposition[Title/Abstract]) AND polymorphism [Title/Abstract]). We identified 38 single-nucleotide polymorphisms that may modulate the genetic adaptive response to training. The identification of genetic marker(s) that improve the beneficial effects of training may in perspective make it possible to assess training programs, which in combination with dietary intervention can optimize body weight reduction in obese subjects, with or without lymphedema. This is particularly important for patients with lymphedema because obesity can worsen the clinical status, and therefore, a personalized approach that could reduce obesity would be fundamental in the clinical management of lymphedema.
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Affiliation(s)
- Andrea Vettori
- Department of Biotechnology, University of Verona, Verona, Italy
| | | | | | - Karen L Herbst
- Department of Medicine, University of Arizona, Tucson, Arizona, USA.,Department of Pharmacy, University of Arizona, Tucson, Arizona, USA.,Department of Medical Imaging, University of Arizona, Tucson, Arizona, USA.,Department of Surgery, University of Arizona, Tucson, Arizona, USA
| | - Marina Cestari
- Study Centre Pianeta Linfedema, Terni, Italy.,Lymphology Sector of the Rehabilitation Service, USLUmbria2, Terni, Italy
| | - Sandro Michelini
- Department of Vascular Rehabilitation, San Giovanni Battista Hospital, Rome, Italy
| | - Serena Michelini
- Unit of Physical Medicine and Rehabilitation, Sant'Andrea Hospital, "Sapienza" University of Rome, Rome, Italy
| | - Michele Samaja
- Department of Health Science, University of Milan-San Paolo Hospital, Milan, Italy
| | - Matteo Bertelli
- MAGI'S Lab, Rovereto, Italy.,MAGI Euregio, Bolzano, Italy.,EBTNA-LAB, Rovereto, Italy
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Sun Y, Ding S. ER-Mitochondria Contacts and Insulin Resistance Modulation through Exercise Intervention. Int J Mol Sci 2020; 21:ijms21249587. [PMID: 33339212 PMCID: PMC7765572 DOI: 10.3390/ijms21249587] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 12/11/2020] [Accepted: 12/14/2020] [Indexed: 12/16/2022] Open
Abstract
The endoplasmic reticulum (ER) makes physical contacts with mitochondria at specific sites, and the hubs between the two organelles are called mitochondria-associated ER membranes (MAMs). MAMs are known to play key roles in biological processes, such as intracellular Ca2+ regulation, lipid trafficking, and metabolism, as well as cell death, etc. Studies demonstrated that dysregulation of MAMs significantly contributed to insulin resistance. Alterations of MAMs’ juxtaposition and integrity, impaired expressions of insulin signaling molecules, disruption of Ca2+ homeostasis, and compromised metabolic flexibility are all actively involved in the above processes. In addition, exercise training is considered as an effective stimulus to ameliorate insulin resistance. Although the underlying mechanisms for exercise-induced improvement in insulin resistance are not fully understood, MAMs may be critical for the beneficial effects of exercise.
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Affiliation(s)
- Yi Sun
- Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China;
- College of Physical Education and Health, East China Normal University, Shanghai 200241, China
| | - Shuzhe Ding
- Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China;
- College of Physical Education and Health, East China Normal University, Shanghai 200241, China
- Correspondence:
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Genders AJ, Holloway GP, Bishop DJ. Are Alterations in Skeletal Muscle Mitochondria a Cause or Consequence of Insulin Resistance? Int J Mol Sci 2020; 21:ijms21186948. [PMID: 32971810 PMCID: PMC7554894 DOI: 10.3390/ijms21186948] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 09/18/2020] [Accepted: 09/18/2020] [Indexed: 12/14/2022] Open
Abstract
As a major site of glucose uptake following a meal, skeletal muscle has an important role in whole-body glucose metabolism. Evidence in humans and animal models of insulin resistance and type 2 diabetes suggests that alterations in mitochondrial characteristics accompany the development of skeletal muscle insulin resistance. However, it is unclear whether changes in mitochondrial content, respiratory function, or substrate oxidation are central to the development of insulin resistance or occur in response to insulin resistance. Thus, this review will aim to evaluate the apparent conflicting information placing mitochondria as a key organelle in the development of insulin resistance in skeletal muscle.
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Affiliation(s)
- Amanda J. Genders
- Institute for Health and Sport (iHeS), Victoria University, Melbourne 8001, Australia;
- Correspondence: ; Tel.: +61-3-9919-9556
| | - Graham P. Holloway
- Dept. Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada;
| | - David J. Bishop
- Institute for Health and Sport (iHeS), Victoria University, Melbourne 8001, Australia;
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