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Molecular Mediators of Exercise: Cross-Organ Communication Promoting Health and Combating Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 July 2025 | Viewed by 7815

Special Issue Editors

Prof. Dr. Jan Bilski

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Guest Editor
Department of Biomechanics and Kinesiology, Faculty of Health Sciences, Jagiellonian University Medical College, 31-008 Cracow, Poland
Interests: inflammatory bowel diseases; colitis; intestinal permeability; leaky gut; intestinal alkaline phosphatase; physical exercise; muscle fat crosstalk; myokines; adipokines
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Tomasz Brzozowski

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Guest Editor
Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland
Interests: brain–gut axis; experimental colitis; intestinal permeability; inflammatory bowel diseases; proinflammatory cytokines; adipokines; myokines; lipopolysaccharide; microbiota; obesity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Physical exercise exerts a profound impact on health and disease. The direct benefits of activity are often associated with improved cardiovascular function and muscle adaptation. However, it also triggers a series of signaling pathways that produce bioactive molecules from different organs in the body, contributing to health benefits. For instance, these molecules, currently known as ‘myokines’, are secretory products of the working muscle that have recently attracted significant attention from basic scientists and clinical practitioners. Myokines, including proteins, miRNAs, and exosomes, are intricately regulated by muscle contraction through mechanical transduction pathways. In particular, individual striated myocytes are involved in paracrine and endocrine communication, not only with each other but also with a wide range of organs and tissues, including adipose tissue, the immune system, the liver, the pancreas, bones, and the brain. Although the term ‘myokine’ traditionally refers to muscle-derived factors, recent research has expanded this perspective. Adipose tissue (adipokines) and liver (hepatokines) also release circulating factors in response to exercise, collectively called ‘exerkines’. These exercise-responsive factors paint a vibrant picture of interorgan communication and coordinated responses to physical activity.

Exerkines are key mediators of exercise-induced adaptations and health benefits. They act through a variety of communication channels and pathways, including paracrine, endocrine (hormonal), and even autocrine, facilitating complex crosstalk between different cells, tissues, and organs. Exerkines encompass cytokines, nucleic acids (miRNAs, mRNAs, and mitochondrial DNA), lipids, and metabolites, often encapsulated within extracellular vesicles.

Understanding the role of these molecules in tissue communication holds promise for treating disorders associated with metabolic diseases and other systems, including the cardiovascular, pulmonary, digestive, nervous, and reproductive systems. This Special Issue aims to highlight this approach by publishing experimental data and reviews addressing these aspects in various experimental and clinical settings. We welcome the submission of topics related to the impact of exercise on disease and health in experimental and clinical studies, with particular emphasis on physiological mediators, intracellular pathways, and pharmacological agents constituting a background for the pharmacotherapy of various disorders.

Prof. Dr. Jan Bilski
Prof. Dr. Tomasz Brzozowski
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • exercise physiology
  • adipokines
  • myokines
  • hepatokines
  • inter-organ communication
  • inflammation
  • insulin sensitivity
  • obesity
  • type 2 diabetes
  • gastrointestinal system
  • cardiovascular system
  • sarcopenia
  • aging
  • osteogenic regulation
  • neurological health
  • nutraceuticals

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Published Papers (4 papers)

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Research

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11 pages, 769 KiB  
Article
Association Between Tissue Accumulation of Skin Autofluorescence, Disease, and Exercise Capacity in Older Adults
by Jun-Young Sung and Jiyoun Kim
Int. J. Mol. Sci. 2025, 26(7), 2913; https://doi.org/10.3390/ijms26072913 - 23 Mar 2025
Viewed by 135
Abstract
As a noninvasive marker of the accumulation of advanced glycation end products, skin autofluorescence is a cost-effective alternative to traditional measurement methods. This study aimed to explore the associations of skin autofluorescence levels with disease, body composition, and physical function in older Korean [...] Read more.
As a noninvasive marker of the accumulation of advanced glycation end products, skin autofluorescence is a cost-effective alternative to traditional measurement methods. This study aimed to explore the associations of skin autofluorescence levels with disease, body composition, and physical function in older Korean adults. The study included 565 older participants (129 men and 436 women) registered across 12 institutions over 3 months in Incheon, South Korea. The noninvasive evaluation of skin autofluorescence was performed utilizing an advanced glycation end product reader mu. Skin autofluorescence, glycated hemoglobin, body composition, and fitness factors were measured. Statistical significance was set at p < 0.05. We confirmed that skin autofluorescence levels were affected by age (>3.4, p < 0.001), metabolic diseases such as diabetes and hypertension (>3.4, p = 0.038), and fitness factors (>3.4, p = 0.035). The fitness factors, which also represented a major indicator of sarcopenia, were found to have a particularly pronounced effect. Our results showed the relationships between skin autofluorescence levels, disease, and fitness factors. We also found that skin autofluorescence may play a role in the expression and measurement of sarcopenia. However, further studies are warranted to validate these results in other populations and establish a clear baseline value for skin autofluorescence levels in South Korea. Full article
(This article belongs to the Special Issue Molecular Mediators of Exercise: Cross-Organ Communication Promoting Health and Combating Disease)
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12 pages, 546 KiB  
Article
Relationship Between Lifestyle and Physical Fitness Among Older Women with Sarcopenia
by Jun-Young Sung, Moon Jin Lee and Jiyoun Kim
Int. J. Mol. Sci. 2025, 26(5), 2205; https://doi.org/10.3390/ijms26052205 - 28 Feb 2025
Cited by 1 | Viewed by 223
Abstract
This cross-sectional study aimed to identify the interactions between lifestyle-related, diagnostic, and physical strength-related sarcopenia factors. The study included 512 female participants aged 60–100 years from Incheon, Republic of Korea, recruited from 12 institutions. Participants engaged in the study from June to August [...] Read more.
This cross-sectional study aimed to identify the interactions between lifestyle-related, diagnostic, and physical strength-related sarcopenia factors. The study included 512 female participants aged 60–100 years from Incheon, Republic of Korea, recruited from 12 institutions. Participants engaged in the study from June to August 2023. We administered questionnaires on demographic characteristics and health indicators and undertook physical measurements, including grip strength and body composition. Hierarchical regression analysis and two-way analysis of variance were conducted to examine the association between sarcopenia and the examined variables. Statistical significance was set at p < 0.05. Hierarchical regression analysis of the variables affecting sarcopenia showed each characteristic’s effect: Model 1 (basic characteristic): R2, 0.391; p < 0.001; Model 2 (Model 1 + additional characteristics): R2, 0.427; p < 0.001. Hierarchical regression analysis of diagnostic and fitness factors affecting sarcopenia also showed an effect on sarcopenia (Model 1 (basic characteristics): R2, 0.318; p < 0.001; Model 2 (Model 1 + body composition): R2, 0.419; p < 0.001; Model 3 (Model 2 + fitness factors): R2, 0.664; p < 0.001). This study enhances the understanding of sarcopenia by investigating its connections with sociodemographic factors, lifestyle choices, and physical activity. The study underscores that lifestyle factors sustainably influence sarcopenia while confirming its correlation with fitness-related factors. Notably, this study highlights the results that muscle function is very important in preventing sarcopenia and that continuous physical activity and types of physical activity affect it. Full article
(This article belongs to the Special Issue Molecular Mediators of Exercise: Cross-Organ Communication Promoting Health and Combating Disease)
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13 pages, 2739 KiB  
Article
Exploring the Impact of Resistance Training at Moderate Altitude on Metabolic Cytokines in Humans: Implications for Adipose Tissue Dynamics
by Sergio Pérez-Regalado, Josefa Leon, Paulino Padial, Cristina Benavente, Filipa Almeida, Juan Bonitch-Góngora, Blanca de la Fuente and Belén Feriche
Int. J. Mol. Sci. 2024, 25(21), 11418; https://doi.org/10.3390/ijms252111418 - 24 Oct 2024
Viewed by 1048
Abstract
Hypobaric hypoxia (HH) limits oxygen supply to tissues and increases metabolic demands, especially during exercise. We studied the influence of HH exposure on the subcutaneous adipose tissue (SAT) thickness and circulating metabolic-related cytokines levels after a resistance training (RT) program. Twenty [...] Read more.
Hypobaric hypoxia (HH) limits oxygen supply to tissues and increases metabolic demands, especially during exercise. We studied the influence of HH exposure on the subcutaneous adipose tissue (SAT) thickness and circulating metabolic-related cytokines levels after a resistance training (RT) program. Twenty trained men participated in a traditional hypertrophy RT for 8 weeks (three sessions/week) under intermittent terrestrial HH (2320 m) or normoxia (N, 690 m) conditions. Before, at week 6, and after the RT, SAT, and vastus lateralis (VL) muscle thickness were measured by ultrasound. Blood samples were taken to analyse serum cytokines (IL-6, IL-15, irisin, and myostatin) by multiplex immunoassay. Our findings revealed a moderate reduction in IL-6 and irisin in HH following the RT (ES < −0.64; p < 0.05). Additionally, RT in HH promoted serum IL-15 release (ES = 0.890; p = 0.062), which exhibited a trivial inverse association with the reductions observed on SAT (−17.69%; p < 0.001) compared with N. RT in HH explained ~50% of SAT variance (p < 0.001). These results highlight the benefit of stressor factors linked to RT in HH on SAT through the modulation of serum metabolic cytokine profiles, suggesting a potential effect on overall body composition. Full article
(This article belongs to the Special Issue Molecular Mediators of Exercise: Cross-Organ Communication Promoting Health and Combating Disease)
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Review

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21 pages, 754 KiB  
Review
The Effects of Blood Flow Restriction Aerobic Exercise on Body Composition, Muscle Strength, Blood Biomarkers, and Cardiovascular Function: A Narrative Review
by Chaeeun Cho and Sewon Lee
Int. J. Mol. Sci. 2024, 25(17), 9274; https://doi.org/10.3390/ijms25179274 - 27 Aug 2024
Viewed by 5691
Abstract
Blood flow restriction exercise has emerged as a promising alternative, particularly for elderly individuals and those unable to participate in high-intensity exercise. However, existing research has predominantly focused on blood flow restriction resistance exercise. There remains a notable gap in understanding the comprehensive [...] Read more.
Blood flow restriction exercise has emerged as a promising alternative, particularly for elderly individuals and those unable to participate in high-intensity exercise. However, existing research has predominantly focused on blood flow restriction resistance exercise. There remains a notable gap in understanding the comprehensive effects of blood flow restriction aerobic exercise (BFRAE) on body composition, lipid profiles, glycemic metabolism, and cardiovascular function. This review aims to explore the physiological effects induced by chronic BFRAE. Chronic BFRAE has been shown to decrease fat mass, increase muscle mass, and enhance muscular strength, potentially benefiting lipid profiles, glycemic metabolism, and overall function. Thus, the BFRAE offers additional benefits beyond traditional aerobic exercise effects. Notably, the BFRAE approach may be particularly suitable for individuals with low fitness levels, those prone to injury, the elderly, obese individuals, and those with metabolic disorders. Full article
(This article belongs to the Special Issue Molecular Mediators of Exercise: Cross-Organ Communication Promoting Health and Combating Disease)
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