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Introduction: Myokines, known to mediate metabolism, inflammation, and other pathophysiological conditions, have been widely investigated, including myokines induced by exercise. However, among published literature, there is substantial inconsistency in the quantification of exercise-induced myokines. Here, we summarized and compared published data...
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Context 1
... the effects of exercise-induced myo- kines, conditions of metabolic disorder are improved [1]. Based on 55 papers reviewed related to myokines, 52.45% of the studies are related to metabolic disorders, showing that exercise-induced myokines could alleviate metabolic dysregu- lation in the patient with metabolic diseases (Figure 3). ...
Context 2
... than half of all myokines such as apelin, irisin, and IL- 15 that we reviewed are secreted from skeletal muscle during/ after exercise and negatively associate with metabolic and chronic diseases such as obesity and diabetes (Figure 3). These results show that physical activity could improve meta- bolic homeostasis of patients with metabolic disorders, emphasizing the importance of analyzing the myokine-related mechanisms in exercise-metabolism axis. ...
Context 3
... this brief review, 24.59% of 55 selected articles are related to aged models and age-mimetic models such as the atrophied muscle model. The common interest of these articles is the plasticity of skeletal muscle such as hyper- trophy or recovering atrophied muscle (Figure 3). SPARC, one of the myokines and also known as osteonectin, is related to muscle atrophy, specifically in type 2 fiber domi- nant muscle [64]. ...
Citations
... 3,4 Indeed, during muscular contractions, skeletal muscle cells secret cytokines called myokines into circulation to exert either paracrine, autocrine, or endocrine effects. [5][6][7][8] From a biological perspective, not only are myokines involved in the regulation of muscle metabolism, but they also mediate crosstalk between muscle and organs, including adipose tissue, bone, the liver, the gut, the pancreas, and the brain. 6,[9][10][11] Myokines are implicated in several processes, including satellite-cell proliferation and migration, control of inflammatory cascade and insulin secretion, regulation of angiogenesis and fatty oxidation, and importantly, direct anti-cancer defense (e.g., reducing cancer cell growth). ...
... These epidemiological investigations have shown that circulating cytokines were significantly associated with sarcopenia (21,22). These studies showed that interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a) were related to the risk of sarcopenia (23,24), whereas other studies showed the risk factor of circulating cytokines was TNF-a, IL-6, IL-8, IL-15, and monocyte chemotactic protein-1 (MCP-1) was demonstrated as a risk factor for sarcopenia (25)(26)(27). The association between sarcopenia and circulating cytokines remains controversial; thus, we still need to perform Mendelian randomization (MR) analysis to identify the association. ...
Introduction
Circulating cytokines were considered to play a critical role in the initiation and propagation of sarcopenia and frailty from observational studies. This study aimed to find the casual association between circulating cytokines and sarcopenia and frailty from a genetic perspective by two-sample Mendelian randomization (MR) analysis.
Methods
Data for 41 circulating cytokines were extracted from the genome-wide association study dataset of 8,293 European participants. Inverse-variance weighted (IVW) method, MR-Egger, and weighted median method were applied to assess the relationship of circulating cytokines with the risk of aging-related syndromes and frailty. Furthermore, MR-Egger regression was used to indicate the directional pleiotropy, and Cochran’s Q test was used to verify the potential heterogeneity. The “leave-one-out” method was applied to visualize whether there was a causal relationship affected by only one anomalous single-nucleotide polymorphisms.
Results
Genetic predisposition to increasing levels of interleukin-10 (IL-10), IL-12, and vascular endothelial growth factor (VEGF) was associated with the higher risk of low hand grip strength according to the IVW method [R = 1.05, 95% CI = 1.01–1.10, P = 0.028, false discovery rate (FDR)–adjusted P = 1.000; OR = 1.03, 95% CI = 1.00–1.07, P = 0.042, FDR-adjusted P = 0.784; OR = 1.02, 95% CI = 1.00–1.05, P = 0.038, FDR-adjusted P = 0.567]. Furthermore, genetically determined higher macrophage colony-stimulating factors (M-CSFs) were associated with a lower presence of appendicular lean mass (OR = 1.01, 95% CI = 1.00–1.02, P = 0.003, FDR-adjusted P = 0.103). Monokine induced by interferon-γ (MIG) and tumor necrosis factor–beta (TNF-β) were associated with a higher risk of frailty (OR = 1.03, 95% CI = 1.01–1.05, P < 0.0001, FDR-adjusted P = 0.012; OR = 1.01, 95% CI = 1.00–1.03, P = 0.013, FDR-adjusted P = 0.259). In this study, we did not find heterogeneity and horizontal pleiotropy between the circulating cytokines and the risk of frailty and sarcopenia.
Conclusion
Genetic predisposition to assess IL-10, IL-12, and VEGF levels was associated with a higher risk of low hand grip strength and M-CSF with the presence of appendicular lean mass. The high levels of TNF-β and MIG were associated with a higher risk of frailty. More studies will be required to explore the molecular biological mechanisms underlying the action of inflammatory factors.
... It is not likely that only one single protein is responsible for the observed effects, but a combination of several mediators in the secretome, including non-protein substances. Interestingly, SPARC has also been described as a myokine [38]. Previously, it has been shown that expression of secreted SPARC was increased in human myotubes during differentiation [39]. ...
The interplay between skeletal muscle and bone is primarily mechanical; however, biochemical crosstalk by secreted mediators has recently gained increased attention. The aim of this study was to investigate metabolic effects of conditioned medium from osteoblasts (OB-CM) on myotubes and vice versa. Human skeletal muscle cells incubated with OB-CM showed increased glucose uptake and oxidation, and mRNA expression of the glucose transporter (GLUT) 1, while fatty acid uptake and oxidation, and mRNA expression of the fatty acid transporter CD36 were decreased. This was supported by proteomic analysis, where expression of proteins involved in glucose uptake, glycolytic pathways, and the TCA cycle were enhanced, and expression of several proteins involved in fatty acid metabolism were reduced. Similar effects on energy metabolism were observed in human bone marrow stromal cells differentiated to osteoblastic cells incubated with conditioned medium from myotubes (SKM-CM), with increased glucose uptake and reduced oleic acid uptake. Proteomic analyses of the two conditioned media revealed many common proteins. Thus, our data may indicate a shift in fuel preference from fatty acid to glucose metabolism in both cell types, induced by conditioned media from the opposite cell type, possibly indicating a more general pattern in communication between these tissues.
... In support of exercise's downregulation of TNF-α, a clinical trial investigating exercise's pro-inflammatory effects showed that in participants infused with Escherichia coli, resting participants to have a two-to threefold increase in TNF-α compared to the participants who performed a cycling exercise earlier that day [66,67]. Furthermore, though the exact pathway is unknown, IL-6 appears to play a significant role [62,63,[67][68][69][70][71][72][73][74][75][76][77][78][79][80][81]. IL-6 is commonly classified as a proinflammatory cytokine, much like TNF-α, however studies suggest it may have anti-inflammatory properties as well, due to its ability, via negative feedback, to decrease the body's levels of TNF-α and other proinflammatory cytokines [70,72,76,80]. ...
... Furthermore, though the exact pathway is unknown, IL-6 appears to play a significant role [62,63,[67][68][69][70][71][72][73][74][75][76][77][78][79][80][81]. IL-6 is commonly classified as a proinflammatory cytokine, much like TNF-α, however studies suggest it may have anti-inflammatory properties as well, due to its ability, via negative feedback, to decrease the body's levels of TNF-α and other proinflammatory cytokines [70,72,76,80]. Levels of IL-6 may be increased up to 100-fold in long-term exercise [63,[74][75][76][77]. ...
Inflammatory skin conditions are significantly impacted by lifestyle habits, particularly those related to diet, exercise, and sleep. Although ancient cultures emphasized the importance of lifestyle behaviors as both etiology and therapy in disease, modern medicine often overlooks nonpharmacological therapy. However, recent studies show that diet can have a significant impact on inflammatory skin diseases such as psoriasis, hidradenitis suppurativa, and atopic dermatitis. Foods high in glycemic index, advanced glycation end-products, and omega-6 polyunsaturated fatty acids are associated with obesity and systemic inflammation, which can exacerbate inflammatory skin diseases. In addition, lifestyle behaviors such as exercise and sleep have been shown to have positive effects on inflammatory skin diseases. This review aims to highlight the importance of lifestyle behaviors in the context of inflammation and inflammatory dermatoses. Key words: Diet, Exercise, Sleep, Psoriasis, Inflammation, Skin
... The quantity of muscle varies greatly among individuals with 35-50 kg in young men and can be as low as ≤ 13 kg in elderly women [3]. With natural aging, muscle mass starts to decline at an age zone of 35-50 years, depending on health status, sex, muscle group, and measurement method [2,[4][5][6][7][8][9][10]. Low muscle mass is associated with a reduced muscle strength (i.e., dynapenia) [11][12][13][14], fitness [15], mobility [14], postural stability [16], release of anti-inflammatory myokines [17], brain gray matter volume [18], therapeutic efficacy [19], and quality of life [20,21]. On the other hand, low age-related muscle mass (i.e., sarcopenia) is associated with an increase in falls [22][23][24], frailty [25], fractures [26], intra-and inter-muscular fat accumulation [27,28], risks for cardiovascular disease [29], incidence of cancer [30][31][32], mental health problems [20,33], cognitive impairment [34], hospitalization [24], morbidity, and mortality [35][36][37][38][39][40][41]. ...
Background
The quantity and quality of skeletal muscle are important determinants of daily function and metabolic health. Various forms of physical exercise can improve muscle function, but this effect can be inconsistent and has not been systematically examined across the health-neurological disease continuum. The purpose of this systematic scoping review with meta-analyses was to determine the effects and potential moderators of exercise training on morphological and neuromuscular muscle quality (MMQ, NMQ) in healthy older individuals. In addition and in the form of a scoping review, we examined the effects of exercise training on NMQ and MMQ in individuals with neurological conditions.
Methods
A systematic literature search was performed in the electronic databases Medline, Embase, and Web of Science. Randomized controlled trials were included that examined the effects of exercise training on muscle quality (MQ) in older individuals with and without neurological conditions. Risk of bias and study quality were assessed (Cochrane Risk of Bias Tool 2.0). We performed random-effects models using robust variance estimation and tested moderators using the approximate Hotelling–Zhang test.
Results
Thirty studies ( n = 1494, 34% females) in healthy older individuals and no studies in individuals with neurological conditions were eligible for inclusion. Exercise training had small effects on MMQ ( g = 0.21, 95% confidence interval [CI]: 0.03–0.40, p = 0.029). Heterogeneity was low (median I ² = 16%). Training and demographic variables did not moderate the effects of exercise on MMQ. There was no association between changes in MMQ and changes in functional outcomes. Exercise training improved NMQ ( g = 0.68, 95% CI 0.35–1.01, p < 0.000) across all studies, in particular in higher-functioning older individuals ( g = 0.72, 95% CI 0.38–1.06, p < 0.001), in lower extremity muscles ( g = 0.74, 95% CI 0.35–1.13, p = 0.001), and after resistance training ( g = 0.91; 95% CI 0.42–1.41, p = 0.001). Heterogeneity was very high (median I ² = 79%). Of the training and demographic variables, only resistance training moderated the exercise-effects on NMQ. High- versus low-intensity exercise moderated the exercise-effects on NMQ, but these effects were considered unreliable due to a low number of studies at high intensity. There was no association between changes in NMQ and changes in functional outcomes.
Conclusion
Exercise training has small effects on MMQ and medium-large effects on NMQ in healthy older individuals. There was no association between improvements in MQ and increases in muscle strength, mobility, and balance. Information on dose-response relations following training is currently lacking. There is a critical gap in muscle quality data for older individuals with lower function and neurological conditions after exercise training. Health practitioners should use resistance training to improve muscle function in older individuals. Well-designed studies are needed to examine the relevance of exercise training-induced changes in MQ in daily function in older individuals, especially to those with lower function and neurological conditions.
... Apelin and FGF-21 are released with exercise-induced muscle contraction and are involved in metabolic regulation by controlling glucose and fat metabolism. As such, these exerkines are implicated in improving insulin sensitivity and preventing obesity and diabetes mellitus with exercise (Son et al., 2018;Khalafi et al., 2021). However, secretion of these exerkines after hypoxic exposure in combination with exercise remains poorly investigated. ...
Purpose: The aim of this study was to investigate the influence of manipulating hypoxic severity with low-intensity exercise on glucose regulation in healthy overweight adults.
Methods: In a randomized crossover design, 14 males with overweight (age: 27 ± 5 years; body mass index (BMI) 27.1 ± 1.8 kg⋅m²) completed three exercise trials involving 60 min aerobic exercise cycling at 90% lactate threshold in normoxia (NM, FiO2 = 20.9%), moderate hypoxia (MH, FiO2 = 16.5%) and high hypoxia (HH, FiO2 = 14.8%). A post-exercise oral glucose tolerance test (OGTT) was performed. Venous blood samples were analyzed for incremental area under the curve (iAUC), plasma glucose and insulin, as well as exerkine concentrations (plasma apelin and fibroblast growth factor 21 [FGF-21]) pre- and post-exercise. A 24-h continuous glucose monitoring (CGM) was used to determine interstitial glucose concentrations. Heart rate, oxygen saturation (SpO2) and perceptual measures were recorded during exercise.
Results: Post-exercise OGTT iAUC for plasma glucose and insulin concentrations were lower in MH vs. control (p = 0.02). Post-exercise interstitial glucose iAUC, plasma apelin and FGF-21 were not different between conditions. Heart rate was higher in HH vs. NM and MH, and MH vs. NM (p < 0.001), while SpO2 was lower in HH vs. NM and MH, and MH vs. NM (p < 0.001). Overall perceived discomfort and leg discomfort were higher in HH vs. NM and MH (p < 0.05), while perceived breathing difficulty was higher in HH vs. NM only (p = 0.003).
Conclusion: Compared to higher hypoxic conditions, performing acute aerobic-based exercise under moderate hypoxia provided a more effective stimulus for improving post-exercise glucose regulation while concomitantly preventing excessive physiological and perceptual stress in healthy overweight adults.
... Of note, there were some inconsistencies in the reported effect of physical exercise on exerkine levels. Some differences might be due to the discrepancy in the quantification of biomarkers, timing of sample collection, pre-analytic sample processing, the analytical method, and calculation of other factors (Son et al., 2018). As an example, studies have described how BDNF levels may differ between measurements due to circadian variability, the time between blood collection and centrifugation, or whether BDNF was measured in serum or in plasma (Cain et al., 2017;Gejl et al., 2019). ...
Physical exercise may improve cognitive function by modulating molecular and cellular mechanisms within the brain. We propose that the facilitation of long-term synaptic potentiation (LTP)-related pathways, by products induced by physical exercise (i.e., exerkines), is a crucial aspect of the exercise-effect on the brain. This review summarizes synaptic pathways that are activated by exerkines and may potentiate LTP. For a total of 16 exerkines, we indicated how blood and brain exerkine levels are altered depending on the type of physical exercise (i.e., cardiovascular or resistance exercise) and how they respond to a single bout (i.e., acute exercise) or multiple bouts of physical exercise (i.e., chronic exercise). This information may be used for designing individualized physical exercise programs. Finally, this review may serve to direct future research towards fundamental gaps in our current knowledge regarding the biophysical interactions between muscle activity and the brain at both cellular and system levels.
... They found it to be beneficial in treating obesity and lowering blood apelin-12 concentrations, which are linked to metabolic syndrome markers [35]. Although there is broad variation in the quantification of myokines caused by exercise among published papers (which may be due to timing of sample selection, pre-analytic sample processing, analytical technique, and estimation, and other factors [36,37] such as form, volume, or strength of exercise), it can be assumed that apelin levels are positively associated with BMI. Furthermore, when the study findings are analyzed indepth, it can be stated that an increase in apelin is found in cases of decreased insulin resistance and improved lipid and glycemic profile after the exercise program. ...
The effects of various strength training intensities on blood cardiovascular risk markers in healthy men Sağlıklı erkeklerde farklı kuvvet egzersizi yoğunluklarının kan kardiyovasküler risk belirteçleri üzerindeki etkileri Abstract Objectives: Regular physical exercise, especially aerobic exercise, is known to have a protective effect on cardio-vascular health. The aim of this research is to look at the impact of two separate resistance training programs on blood biomarkers that are associated with the early detection of cardiac risk. Methods: Forty-five male participants (mean 41 years) were randomly divided into three groups: The low-intensity resistance exercise group (LIEG), the moderate-intensity resistance exercise group (MIEG), and the control group (CG). The programs were implemented three times a week and in two sets. MIEG consisted of 8-10 repeats at 70-80% density of one repetition maximum load (1RM), while LIEG consisted of 15-17 repeats at 50-60% density of 1RM. CG did not participate in any exercise program. Two-factor mixed-design ANOVA assessed the data. Results: Before, fourth week, and after the exercise program in repeated measurements, there was a significant decrease in body mass (−1.7%), body mass index (−1.7%), apelin (−44%), and pentraxin 3 (−39%) levels in MIEG (p < 0.05). Additionally, our study noted a decrease in pentraxin 3 (−25%, p < 0.05) and interleukin 6 (−21%) levels, while there was an increase in creatine kinase (18%), and lactate dehydrogenase (7.4%) levels in LIEG. Strength levels improved significantly in exercise groups. Conclusions: Eight weeks of moderate-resistance training can potentially reduce the cardiovascular risk in healthy men. Öz Amaç: Düzenli fiziksel egzersizin, özellikle aerobik egzersi-zin, kardiyovasküler sağlık üzerinde koruyucu bir etkisi olduğu bilinmektedir. Bu çalışmada amaç, iki farklı yoğun-luktaki direnç egzersiz programının kardiyak riskin erken teşhisinde yer alan kan belirteçleri üzerindeki etkilerini araştırmaktır. Gereç ve Yöntem: Kırk beş erkek katılımcı (ort. 41 yaş) rastgele üç gruba ayrıldı: Düşük yoğunluklu direnç egzersiz grubu (LIEG), orta yoğunluklu direnç egzersiz grubu (MIEG)
... For each subcategory of exercise factors (i.e., metabolites, nucleic acids, and proteins), the number of individual molecules that are reported to change in response to acute exercise is often estimated to be hundreds (Fernández-Sanjurjo et al., 2018;Sakaguchi et al., 2019;Guseh et al., 2020). A small number of molecules may decrease in abundance in response to acute exercise, but it is generally considered that the majority of changes in exercise factors are in the form of increased circulating abundance(s; Fernández-Sanjurjo et al., 2018;Son et al., 2018;Murphy et al., 2020;Severinsen and Pedersen, 2020). Some individual factors are well-described and understood in terms of the kinetics of their response to exercise and subsequent metabolic and/or molecular effects, such as the metabolite lactate (van Hall, 2010;Brooks et al., 2021), and the myokine interleukin-6 (IL-6; Pedersen and Febbraio, 2008). ...
... Detailed discussion of these reports is beyond the scope of this review, but collectively the training-induced response is equivocal; some factors increase after a period of exercise training, while others decrease, with occasional inconsistencies in individual factors across studies. Again, variations in experimental design and sample timing described in the section "Study Design Considerations for Investigating the Adaptive Response to Exercise Training" must be considered, and interested readers are referred to reviews with appropriately collated tables of these studies for miRNA (Fernández-Sanjurjo et al., 2018) and protein (Son et al., 2018). ...
In response to acute exercise, an array of metabolites, nucleic acids, and proteins are enriched in circulation. Collectively termed “exercise factors,” these molecules represent a topical area of research given their speculated contribution to both acute exercise metabolism and adaptation to exercise training. In addition to acute changes induced by exercise, the resting profile of circulating exercise factors may be altered by exercise training. Many exercise factors are speculated to be transported in circulation as the cargo of extracellular vesicles (EVs), and in particular, a sub-category termed “small EVs.” This review describes an overview of exercise factors, small EVs and the effects of exercise, but is specifically focused on a critical appraisal of methodological approaches and current knowledge in the context of changes in the resting profile small EVs induced by exercise training, and the potential bioactivities of preparations of these “exercise-trained” small EVs. Research to date can only be considered preliminary, with interpretation of many studies hindered by limited evidence for the rigorous identification of small EVs, and the conflation of acute and chronic responses to exercise due to sample timing in proximity to exercise. Further research that places a greater emphasis on the rigorous identification of small EVs, and interrogation of potential bioactivity is required to establish more detailed descriptions of the response of small EVs to exercise training, and consequent effects on exercise adaptation.
... They found it to be beneficial in treating obesity and lowering blood apelin-12 concentrations, which are linked to metabolic syndrome markers [35]. Although there is broad variation in the quantification of myokines caused by exercise among published papers (which may be due to timing of sample selection, pre-analytic sample processing, analytical technique, and estimation, and other factors [36,37] such as form, volume, or strength of exercise), it can be assumed that apelin levels are positively associated with BMI. Furthermore, when the study findings are analyzed indepth, it can be stated that an increase in apelin is found in cases of decreased insulin resistance and improved lipid and glycemic profile after the exercise program. ...
Objectives
Regular physical exercise, especially aerobic exercise, is known to have a protective effect on cardiovascular health. The aim of this research is to look at the impact of two separate resistance training programs on blood biomarkers that are associated with the early detection of cardiac risk.
Methods
Forty-five male participants (mean 41 years) were randomly divided into three groups: The low-intensity resistance exercise group (LIEG), the moderate-intensity resistance exercise group (MIEG), and the control group (CG). The programs were implemented three times a week and in two sets. MIEG consisted of 8–10 repeats at 70–80% density of one repetition maximum load (1RM), while LIEG consisted of 15–17 repeats at 50–60% density of 1RM. CG did not participate in any exercise program. Two-factor mixed-design ANOVA assessed the data.
Results
Before, fourth week, and after the exercise program in repeated measurements, there was a significant decrease in body mass (−1.7%), body mass index (−1.7%), apelin (−44%), and pentraxin 3 (−39%) levels in MIEG (p < 0.05). Additionally, our study noted a decrease in pentraxin 3 (−25%, p < 0.05) and interleukin 6 (−21%) levels, while there was an increase in creatine kinase (18%), and lactate dehydrogenase (7.4%) levels in LIEG. Strength levels improved significantly in exercise groups.
Conclusions
Eight weeks of moderate-resistance training can potentially reduce the cardiovascular risk in healthy men.
