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Physical Exercise and Myokines: Relationships with Sarcopenia and Cardiovascular Complications
Open accessAbstract
Skeletal muscle is capable of secreting different factors in order to communicate with other tissues. These mediators, the myokines, show potentially far-reaching effects on non-muscle tissues and can provide a molecular interaction between muscle and body physiology. Sarcopenia is a chronic degenerative neuromuscular disease closely related to cardiomyopathy and chronic heart failure, which influences the production and release of myokines. Our objective was to explore the relationship between myokines, sarcopenia, and cardiovascular diseases (CVD). The autocrine, paracrine, and endocrine actions of myokines include regulation of energy expenditure, insulin sensitivity, lipolysis, free fatty acid oxidation, adipocyte browning, glycogenolysis, glycogenesis, and general metabolism. A sedentary lifestyle accelerates the aging process and is a risk factor for developing sarcopenia, metabolic syndrome, and CVD. Increased adipose tissue resulting from the decrease in muscle mass in patients with sarcopenia may also be involved in the pathology of CVD. Myokines are protagonists in the complex condition of sarcopenia, which is associated with adverse clinical outcomes in patients with CVD. The discovery of new pathways and the link between myokines and CVD remain a cornerstone toward multifaceted interventions and perhaps the minimization of the damage resulting from muscle loss induced by factors such as atherosclerosis.
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“This environment constitutes fertile soil for atherosclerosis’s chronic inflammatory process, a prelude to several cardiovascular conditions [8].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [8]
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BackgroundRütti, S., Dusaulcy, R., Hansen, J. S., Howald, C., Dermitzakis, E. T., Pedersen, B. K., Pinget, M., Plomgaard, P., & Bouzakri, K. (2018) · Scientific Reports · doi:10.1038/s41598-018-28117-2 · Cited by 43
Targeting mitochondrial quality control for treating sarcopenia: lessons from physical exercise
Picca, A., Calvani, R., Leeuwenburgh, C., Coelho‐Júnior, H. J., Bernabei, R., Landi, F., & Marzetti, E. (2018) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2019.1559827 · Cited by 43 · cited 1×
“Moreover, it suppresses the transcription of autophagy genes and can act alone or in synergy with the activation of the IGF-1/PI3K/Akt/mTOR pathway [50].”
BackgroundPrestroke Sarcopenia and Stroke Severity in Elderly Patients with Acute Stroke
Nozoe, M., Kanai, M., Kubo, H., Yamamoto, M., Shimada, S., & Mase, K. (2019) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2019.05.001 · Cited by 42 · cited 1×
“[88] showed that the appearance of pre-stroke sarcopenia is an independent predictor of moderate to severe stroke.”
BackgroundSantana, N. D. M., Mendes, R. M. L., da Silva, N. F., & Pinho, C. P. S. (2019) · Einstein (São Paulo) · doi:10.31744/einstein_journal/2019ao4632 · Cited by 40 · cited 1×
“[90] investigated the value of sarcopenia per se and sarcopenia related to obesity as prognostic predictors of coronary heart disease.”
BackgroundThe brown bear as a translational model for sedentary lifestyle‐related diseases
Fröbert, O., Frøbert, A. M., Kindberg, J., Arnemo, J. M., & Overgaard, M. T. (2019) · Journal of Internal Medicine · doi:10.1111/joim.12983 · Cited by 40 · cited 1×
“A sedentary lifestyle hastens the aging process, putting an individual at significant risk for developing sarcopenia, metabolic syndrome, and CVD [92,93].”
BackgroundExercise and Cardiovascular Protection
Li, G., Li, J., & Gao, F. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-1792-1_14 · Cited by 39 · cited 1×
“In human muscle, the expression of the fibronectin type III domain-containing protein 5 (FNDC5) gene, which encodes a precursor of irisin, is associated with the practice of physical activity and the increase in skeletal muscle mass [96,100,101].”
BackgroundExercise-induced myokines: a brief review of controversial issues of this decade
Son, J. S., Chae, S. A., Testroet, E. D., Du, ., & Jun, H.-P. (2017) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2018.1416290 · Cited by 38 · cited 1×
“[82] suggested that both irisin and SPARC could work as therapeutic mediators to avoid muscle atrophy and sarcopenia.”
BackgroundRole of irisin in androgen-deficient muscle wasting and osteopenia in mice
Iemura, S., Kawao, N., Okumoto, K., Akagi, M., & Kaji, H. (2019) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-019-01043-7 · Cited by 37
Association between reduced brain-derived neurotrophic factor concentration & coronary heart disease
Šustar, A., Perkovic, M. N., Erjavec, G. N., Strac, D. S., & Pivac, N. (2019) · The Indian Journal of Medical Research · doi:10.4103/ijmr.ijmr_1566_17 · Cited by 37
Updated concept of sarcopenia based on muscle–bone relationship
Yakabe, M., Hosoi, T., Akishita, M., & Ogawa, S. (2019) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-019-01048-2 · Cited by 37 · cited 2×
“It is considered a public health problem, in light of its possible adverse outcomes [39,62,63].”
BackgroundYamashita, M., Kamiya, K., Matsunaga, A., Kitamura, T., Hamazaki, N., Matsuzawa, R., Nozaki, K., Tanaka, S., Nakamura, T., Maekawa, E., et al. (2019) · Journal of Cardiology · doi:10.1016/j.jjcc.2019.02.010 · Cited by 35 · cited 1×
“The results of this study showed that sarcopenic obesity is closely associated with an increased risk of mortality in this group of patients [91].”
BackgroundTibana, R. A., Nascimento, D. D. C., de Souza, N. M. F., de Souza, V. C., Neto, I. V. D. S., Voltarelli, F. A., Pereira, G. B., Navalta, J. W., & Prestes, J. (2016) · The journal of nutrition health & aging · doi:10.1007/s12603-016-0748-4 · Cited by 34 · cited 1×
“Considering these premises, if the endocrine role of muscle is not sufficiently stimulated by physical activity, the production and release of myokines may not be enough, contributing to the malfunction of many organs; with time, this biological scenario may lead to the development of frailty [59,69,70].”
BackgroundGonzález-Gil, A. M., Peschard-Franco, M., Castillo, E. C., Gutierrez-DelBosque, G., Treviño, V., Silva‐Platas, C., Pérez-Villarreal, L. F., García‐Rivas, G., & Elizondo‐Montemayor, L. (2019) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-019-0458-2 · Cited by 34 · cited 1×
“Irisin is termed an adipo-myokine, because it can be produced by white adipose and muscle tissue in response to exercise [53,54].”
BackgroundNakano, I., Kinugawa, S., Hori, H., Fukushima, A., Yokota, T., Takada, S., Kakutani, N., Obata, Y., Yamanashi, K., & Anzai, T. (2020) · International Heart Journal · doi:10.1536/ihj.19-400 · Cited by 34
Kim, J., Lee, Y., & Yi, H. (2016) · Experimental Physiology · doi:10.1113/ep085852 · Cited by 33 · cited 3×
“Some of the other myokines are apelin, brain-derived neurotrophic factor (BDNF), angiopoietin-like 4 (ANGPTL4), BAIBA (β-aminoisobutyric acid, a non-protein amino acid), fibroblast growth factor 21 (FGF-21), chemokine (C–”
BackgroundTime-restricted eating and age-related muscle loss
Tinsley, G. M., & Paoli, A. (2019) · Aging · doi:10.18632/aging.102384 · Cited by 24 · cited 1×
“The term that refers to this process is sarcopenia, which derives from sarx (which means “flesh”) and -penia (which implies “loss”) [7,8].”
BackgroundDeveloping Insulin and BDNF Mimetics for Diabetes Therapy
Chan, C. B., Ahuja, P., & Ye, K. (2019) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666191010160643 · Cited by 24
Identification of decorin derived peptides with a zinc dependent anti-myostatin activity
Guiraud, S., van Wittenberghe, L., Georger, C., Scherman, D., & Kichler, A. (2012) · Neuromuscular Disorders · doi:10.1016/j.nmd.2012.07.002 · Cited by 20
Identification of CCL5/RANTES as a novel contraction-reducible myokine in mouse skeletal muscle
Ishiuchi, Y., Sato, H., Komatsu, N., Kawaguchi, H., Matsuwaki, T., Yamanouchi, K., Nishihara, M., & Nedachi, T. (2018) · Cytokine · doi:10.1016/j.cyto.2018.03.012 · Cited by 17
Body Composition in Patients with Atrial Fibrillation.
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“[89] in a cohort study showed that patients with atrial fibrillation had a higher body mass index, larger waist circumference and visceral adiposity, higher values for fat and fat-free Figure 2.”
BackgroundOjima, K., Oe, M., Nakajima, I., Shibata, M., Muroya, S., CHIKUNI, K., Hattori, A., & Nishimura, T. (2014) · Animal Science Journal · doi:10.1111/asj.12310 · Cited by 16
Abe, K., Yano, T., Katano, S., Ohori, K., Ishigo, T., Moniwa, N., & Miura, T. (2020) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.13876 · Cited by 15
Design and synthesis of potent myostatin inhibitory cyclic peptides
Rentier, C., Takayama, K., Saitoh, M., Nakamura, A., Ikeyama, H., Taguchi, A., Taniguchi, A., & Hayashi, Y. (2019) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.02.019 · Cited by 11 · cited 1×
“Genetic defects causing decreased myostatin production result in muscle hypertrophy, while the overexpression of this myokine induces cachexia [38].”
BackgroundCirculating MicroRNAs as Diagnostic Biomarkers for Motor Neuron Disease
Wang, L., & Zhang, L. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00354 · Cited by 9
Myokines: A promising therapeutic target for hepatic encephalopathy
Yang, C., & Luo, A. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2016.10.040 · Cited by 8
Newly discovered myokines in chronic kidney disease
Ebert, T., & Kralisch, S. (2016) · Polskie Archiwum Medycyny Wewnętrznej · doi:10.20452/pamw.3473 · Cited by 6 · cited 1×
“Irisin is an independent parameter associated with sarcopenia and carotid atherosclerosis [24] in dialysis patients, which suggests its significant role in CVD, at least in part, independently of inflammation that occurs in these patients [55].”
BackgroundNguyen, T. V., Tran, K. D., Bui, K. X., Le, D., & Nguyen, T. N. (2020) · Australian Journal on Ageing · doi:10.1111/ajag.12789 · Cited by 4 · cited 1×
“A sedentary lifestyle hastens the aging process, putting an individual at significant risk for developing sarcopenia, metabolic syndrome, and CVD [92,93].”
BackgroundApelin affects the mouse aging urinary peptidome with minimal effects on kidney
Vinel, C., Schanstra, J. P., Boizard, F., Péreira, O., Auriau, J., Dortignac, A., Breuil, B., Feuillet, G., Nkuipou‐Kenfack, E., Zürbig, P., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-47109-4 · Cited by 3
Cited by
Sorted by citations
El Assar, M., Álvarez-Bustos, A., Sosa, P., Angulo, J., & Rodríguez-Mañas, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158713 · Cited by 371
“Myokine alteration Apelin increases mitocondriogenesis and reduces inflammation Myostatin inhibits muscle synthesis and promotes muscle catabolism and is inhibited by follistatin Adiponectin increases mitochondrial function and augments oxidative fibers Irisin improves mitochondrial function decreases ROS production a…”
BackgroundMetabolic Syndrome and Sarcopenia
Nishikawa, H., Asai, A., Fukunishi, S., Nishiguchi, S., & Higuchi, K. (2021) · Nutrients · doi:10.3390/nu13103519 · Cited by 343
“associated with muscle fiber proliferation) and IGF-1, which have muscle-protein-synthesispromoting effects, and conversely decreases myostatin, which has muscle-protein-synthesisinhibiting effects [95].”
BackgroundBilski, J., Pierzchalski, P., Szczepanik, M., Bonior, J., & Zoladz, J. A. (2022) · Cells · doi:10.3390/cells11010160 · Cited by 271
“They are released in response to exercise; many counteract visceral obesity and IR and play a role in myogenesis [111,433,434].”
BackgroundLinks between metabolic syndrome and metabolic dysfunction-associated fatty liver disease
Lim, S. K., Kim, J., & Targher, G. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.04.008 · Cited by 224
Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions
de Oliveira dos Santos, A. R., de Oliveira Zanuso, B., Miola, V. F. B., Barbalho, S. M., Santos Bueno, P. C., Flato, U. A. P., Detregiachi, C. R. P., Buchaim, D. V., Buchaim, R. L., Tofano, R. J., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052639 · Cited by 189
“This myokine shows positive effects on the cardiovascular system, which may reveal a potential therapeutic target in CVD treatment [8].”
BackgroundInfluentialSelf-citation
Metadata
- Authors
- Barbalho, S. M., Flato, U. A. P., Tofano, R. J., Goulart, R. D. A., Guiguer, E. L., Detregiachi, C. R. P., Buchaim, D. V., Araújo, A. C., Buchaim, R. L., Reina, F. T. R., Biteli, P., Reina, D. O. B. R., & Bechara, M. D.
- Affiliations
- Faculdade de Medicina de Marília (BR)
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenue Hygino Muzzy Filho, 1001, Marília 17525-902, São Paulo, Brazil
- Universidade de Marília (BR)
- Universidade de São Paulo (BR)
- Corresponding author
- Barbalho, Sandra Maria
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2020-05-20
- Volume
- 21
- Issue
- 10
- Pages
- 3607
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7279354
- OpenAlex
- W3028055237
- Cited by
- 156
- References
- 107
- Citations by year
- 2026: 18 · 2025: 23 · 2024: 26 · 2023: 27 · 2022: 40 · 2021: 20 · 2020: 2
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Keywords
- myokines, sarcopenia, cardiovascular disease, physical activity, skeletal muscle, sedentary lifestyle, cardiomyopathy, chronic heart failure, metabolic syndrome, adipose tissue, muscle mass loss, atherosclerosis, insulin sensitivity, energy expenditure
- MeSH terms
- Animals, Cardiovascular Diseases, Cell Communication, Humans, Exercise, Cytokines, Muscle, Skeletal, Adipokines, Sarcopenia
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