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New Insights into Skeletal Muscle Metabolism in Pathological and Physiological...
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New Insights into Skeletal Muscle Metabolism in Pathological and Physiological Conditions

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Cell Biology".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 4740

Special Issue Editor

Dr. Cristina Antinozzi

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Guest Editor
Unit of Endocrinology, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Piazza Lauro de Bosis, 006-00135 Rome, Italy
Interests: cellular biology; cell metabolism; skeletal muscle; hormones; gender medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Skeletal muscle represents the higher section of our body mass. In addition to its role in locomotion, it plays a pivotal role in vascular system working, energy metabolism, hormone homeostasis, inflammation, and so on.  Given these important roles, it comes as no surprise that diseases or conditions that negatively impact skeletal muscle can have major consequences on health and longevity, leading to the development of muscular diseases such as dystrophies, dysfunction, cancer, metabolic disease, and early death. However, the mechanisms that cause these diseases are not still well described, nor is the explanation for why some of these range from mild trouble to life-threatening conditions. Thus, studies aimed at understanding the molecular mechanisms, underliyng skeletal muscle physiology, health lifestyles, and/or new pharmaceutical interventions for muscle strenght, mass, tissue function, and muscle disease conditions are pivotal for a translational approach in broad clinical practice.

The aim of this Special Issue, “New Insights into Skeletal Muscle Metabolism in Pathological and Physiological Conditions,” is to highlight promising studies focusing on the cell mechanisms of muscle metabolism as well as the pathogenesis, management, and prevention of skeletal muscle diseases. We welcome different types of manuscript submissions, such as original articles, narrative reviews, systematic reviews, and meta-analyses concerning any aspect of cellular and molecular mechanism regarding skeletal muscle physiology, to provide a state-of-the-art overview of this Special Issue.

I look forward to receiving your contributions.

Dr. Cristina Antinozzi
Guest Editor

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. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • skeletal muscle
  • muscle diseases
  • hormones
  • physical exercise
  • muscle physiology
  • biomarkers
  • disease prevention
  • antibodies
  • pharmacological approaches
  • cell metabolism

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Published Papers (6 papers)

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Research

26 pages, 12086 KiB  
Article
Multi-Omics Identification of Fos as a Central Regulator in Skeletal Muscle Adaptation to Long-Term Aerobic Exercise
by Chaoyang Li, Xinyuan Zhu and Yi Yan
Biology 2025, 14(6), 596; https://doi.org/10.3390/biology14060596 - 24 May 2025
Abstract
Skeletal muscle health and function are closely linked to long-term aerobic exercise, particularly in enhancing muscle metabolism and regulating gene expression. Regular endurance training can significantly ameliorate metabolic dysfunction and prevent chronic diseases. However, the precise molecular mechanisms underlying skeletal muscle adaptations to [...] Read more.
Skeletal muscle health and function are closely linked to long-term aerobic exercise, particularly in enhancing muscle metabolism and regulating gene expression. Regular endurance training can significantly ameliorate metabolic dysfunction and prevent chronic diseases. However, the precise molecular mechanisms underlying skeletal muscle adaptations to long-term aerobic exercise require further clarification. To address this, we integrated transcriptomic and single-cell omics datasets from multiple long-term aerobic exercise models retrieved from the GEO database. After merging and batch correction, differential expression analysis identified 204 DEGs, including 110 upregulated and 94 downregulated genes. Key feature genes were screened using Lasso regression, SVM-RFE, and Random Forest machine learning algorithms, validated by RT-qPCR, and refined through PPI network analysis. Among them, Fos and Tnfrsf12a were significantly downregulated following long-term aerobic exercise. Notably, Fos exhibited a more pronounced decrease than Tnfrsf12a, and was strongly associated with inflammation and muscle regeneration. PPI network analysis indicated that Fos interacted with genes such as Casp3, Egr1, Aft3, Hspa5, Src, and Igf2. GO, KEGG, and GSEA enrichment analyses revealed that Fos is involved in skeletal muscle differentiation, tissue remodeling, and the NF-κB inflammatory pathway. ssGSEA analysis further showed that samples with low Fos expression had significantly elevated Th1/Th2 and Treg cell infiltration. Single-cell analysis confirmed preferential Fos expression in muscle fiber/adipocyte progenitors, satellite cells, and tenocytes, all critical for myogenesis. In summary, our findings suggest that long-term aerobic exercise downregulates Fos, potentially alleviating inflammation and enhancing satellite cell-mediated muscle regeneration. Fos may serve as a central regulator of skeletal muscle remodeling during long-term aerobic exercise. Full article
(This article belongs to the Special Issue New Insights into Skeletal Muscle Metabolism in Pathological and Physiological Conditions)
15 pages, 1656 KiB  
Article
Deciphering the Role of Ferroptosis in the Pathogenesis of Peripheral Artery Disease Myopathy
by Trevor Wilkinson, Emma Fletcher, Andrew Ring, Cassandra Bradley, Evlampia Papoutsi, Dimitrios Miserlis, Robert S. Smith, William T. Bohannon, Iraklis I. Pipinos and Panagiotis Koutakis
Biology 2025, 14(5), 537; https://doi.org/10.3390/biology14050537 - 12 May 2025
Viewed by 267
Abstract
This study investigates ferroptosis in the context of peripheral artery disease (PAD), a vascular disease characterized by atherosclerosis of the lower extremities. Muscle atrophy and increased oxidative stress are hallmarks of PAD and correlate with worse clinical outcomes. Given ferroptosis’ association with oxidative [...] Read more.
This study investigates ferroptosis in the context of peripheral artery disease (PAD), a vascular disease characterized by atherosclerosis of the lower extremities. Muscle atrophy and increased oxidative stress are hallmarks of PAD and correlate with worse clinical outcomes. Given ferroptosis’ association with oxidative stress, we explored its role in PAD myopathy by examining gene and protein markers related to metabolic pathways implicated in ferroptosis using both human PAD patients and cultured myotubes. Intermittent claudication (IC) PAD patients, critical limb ischemia (CLI) PAD patients, and non-PAD controls were recruited for this study. Calf muscle biopsies were analyzed for gene expression using qPCR, and protein levels were determined by Western blotting. Cultured myotubes treated with the ferroptosis inducer erastin provided an in vitro comparison. Results demonstrated upregulation of ferroptosis markers such as lipid peroxidation and PTGS2 gene expression in the muscle of CLI PAD patients compared to controls. Increased expression of ferroptosis-related genes HMOX1, ACSL4, ELAVL1, and Beclin-1 was also observed. Protein analysis showed trends consistent with gene expression in some ferroptosis markers. The increase in ferroptosis markers in CLI PAD patients, particularly in iron metabolism and autophagy pathways, suggests ferroptosis contributes to PAD myopathy. Full article
(This article belongs to the Special Issue New Insights into Skeletal Muscle Metabolism in Pathological and Physiological Conditions)
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18 pages, 1445 KiB  
Article
A Single Intraperitoneal Secreted Protein Acidic and Rich in Cysteine Injection in Mice Is Towards an Exercise-like Phenotype
by Abdelaziz Ghanemi, Mayumi Yoshioka and Jonny St-Amand
Biology 2025, 14(4), 398; https://doi.org/10.3390/biology14040398 - 10 Apr 2025
Viewed by 375
Abstract
Secreted protein acidic and rich in cysteine (SPARC) is a protein widely expressed in various tissues. The metabolic and functional exploration of SPARC indicated it as a mediator of the exercise-induced effects. Furthermore, SPARC overexpression mimics exercise effects (including anti-aging phenotype), whereas its [...] Read more.
Secreted protein acidic and rich in cysteine (SPARC) is a protein widely expressed in various tissues. The metabolic and functional exploration of SPARC indicated it as a mediator of the exercise-induced effects. Furthermore, SPARC overexpression mimics exercise effects (including anti-aging phenotype), whereas its knockout both reduces the exercise-induced phenotype and increases aging. Each of these previous studies has been carried out for weeks and, therefore, indicates chronic effects of SPARC. To complete the puzzle, there is a need to explore the acute effects of SPARC. Thus, this study reports results of selected molecular and metabolic explorations of mice following a single injection of SPARC. Following both a validation of the Western blot as a detection method of SPARC in the serum and the optimization of the post-injection sacrifice time, mice (male and female) were injected with either SPARC or saline and sacrificed after 4 h. Body weight, selected tissues weights, and glycemia were measured. Muscle (tibialis anterior)—that was also harvested after the sacrifice and frozen—was used to measure the expression of selected proteins related to metabolism, protein hemostasis, and muscle development. Briefly, the results indicate a protein expression pattern towards improved glucose metabolism, oxidative phosphorylation, mitochondrial biogenesis, extracellular matrix remodeling, myogenesis, and protein synthesis. On the other hand, the expression of other proteins is towards decreased muscle protein degradation. There were no significant effects of SPARC injection on glycemia. These findings represent an important step towards developing a pharmacology based on injecting SPARC to achieve therapeutic effects that basically mimic exercise benefits, including anti-aging, metabolic enhancement, and muscle development. This is of particular importance for individuals who are unable to perform the required physical activity due to physical disabilities, aging, or hospitalization. Full article
(This article belongs to the Special Issue New Insights into Skeletal Muscle Metabolism in Pathological and Physiological Conditions)
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11 pages, 375 KiB  
Article
Caffeine Supplementation Is Beneficial for the Pulling Performance of Indoor Tug-of-War Athletes
by Chuan-Pao Lin, Ting-Ting Lee and Tzai-Li Li
Biology 2025, 14(4), 354; https://doi.org/10.3390/biology14040354 - 28 Mar 2025
Viewed by 379
Abstract
This study investigated the effects of caffeine supplementation, carbohydrate mouth rinsing, and combined caffeine supplementation with carbohydrate mouth rinsing on the pulling performance and ratings of perceived exertion in indoor tug-of-war athletes. Eighteen tug-of-war athletes were recruited as participants. They underwent four supplementation [...] Read more.
This study investigated the effects of caffeine supplementation, carbohydrate mouth rinsing, and combined caffeine supplementation with carbohydrate mouth rinsing on the pulling performance and ratings of perceived exertion in indoor tug-of-war athletes. Eighteen tug-of-war athletes were recruited as participants. They underwent four supplementation protocols in a double-blind, single-factor, repeated-measures design: caffeine supplementation (CAF), carbohydrate solution mouth rinsing (CHO), combined caffeine supplementation with carbohydrate mouth rinsing (CAF-CHO), and a placebo (PLA). Each participant performed a maximal pulling test at 80% of their maximum pulling force, and the duration was recorded. Ratings of perceived exertion were also assessed. Data were analyzed using SPSS version 25.0 for Windows, and effect sizes (ES) were calculated. The main findings were as follows: (1) The CAF-CHO group showed a significantly longer pulling duration than the PLA and CHO groups (165.0 ± 69.2 s vs. 137.4 ± 48.9 s vs. 135.6 ± 66.6 s). (2) The CAF group also demonstrated a significantly longer pulling duration than the CHO group (162.0 ± 14.1 s vs. 135.6 ± 66.6 s). (3) Both the CAF-CHO and CAF groups exhibited large effect sizes (ω2 > 0.14) compared to the PLA and CHO groups. Both caffeine supplementation combined with carbohydrate mouth rinsing and caffeine supplementation alone can significantly enhance the duration of 80% maximal pulling performance in indoor tug-of-war athletes, with the primary effect attributed to caffeine. These results provide practical strategies for coaches and athletes to suppress fatigue and improve pulling performance during competitions or training sessions for indoor tug-of-war. Full article
(This article belongs to the Special Issue New Insights into Skeletal Muscle Metabolism in Pathological and Physiological Conditions)
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16 pages, 1617 KiB  
Article
Impact of Ad Libitum Hydration on Muscle and Liver Damage and Electrolyte Balance in Ultra-Trail Events: A Heatmap Analysis of Biomarkers and Event Characteristics—A Pilot Study
by Alejandro García-Giménez, Francisco Pradas, Miguel Lecina, Nicolae Ochiana and Carlos Castellar-Otín
Biology 2025, 14(2), 136; https://doi.org/10.3390/biology14020136 - 28 Jan 2025
Viewed by 1124
Abstract
Ultra-trail events (UTs) pose significant challenges to maintaining hydration and electrolyte balance, with risks of dehydration (DH), overhydration (OH), exercise-associated hyponatremia (EAH), and exertional rhabdomyolysis (ER). This study examined the effects of ad libitum (ADL) hydration on hydration status and muscle damage during [...] Read more.
Ultra-trail events (UTs) pose significant challenges to maintaining hydration and electrolyte balance, with risks of dehydration (DH), overhydration (OH), exercise-associated hyponatremia (EAH), and exertional rhabdomyolysis (ER). This study examined the effects of ad libitum (ADL) hydration on hydration status and muscle damage during a nine-stage UT (635 km, 40,586 m elevation gain). Four highly trained male athletes participated. Hydration was assessed via body weight loss (BWL), urine specific gravity (Usg), and serum sodium ([Na+]), while muscle damage markers included creatine kinase (CK), lactate dehydrogenase (LDH), and calcium (Ca), and liver damage biomarkers included aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Our results showed no cases of EAH or hypernatremia ([Na+] > 145 mmol·L−1), with serum [Na+] maintained above 135 mmol·L−1. BWL exceeded the 2% DH threshold in early stages (p = 0.029), and Usg remained elevated (>1.020 g·mL−1). LDH and CK significantly increased at all stages (p < 0.05), persisting for 48 h post-event. Correlations showed BWL aggravated muscle damage (r = 0.47 with CK) and hypocalcemia (r = −0.68 with Ca). Elevation gain/loss amplified fluid loss and muscle injury. While ADL hydration mitigated EAH, it did not fully address DH or muscle damage. Personalized hydration and recovery protocols are crucial to optimizing performance and health in UT events. Full article
(This article belongs to the Special Issue New Insights into Skeletal Muscle Metabolism in Pathological and Physiological Conditions)
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12 pages, 819 KiB  
Communication
Sexual Dimorphism in Sex Hormone Metabolism in Human Skeletal Muscle Cells in Response to Different Testosterone Exposure
by Paolo Sgrò, Cristina Antinozzi, Christopher W. Wasson, Francesco Del Galdo, Ivan Dimauro and Luigi Di Luigi
Biology 2024, 13(10), 796; https://doi.org/10.3390/biology13100796 - 5 Oct 2024
Cited by 1 | Viewed by 1756
Abstract
Muscle tissue is an important target of sex steroids, and particularly, testosterone plays essential roles in muscle cell metabolism. Wide ranges of studies have reported sex differences in basal muscle steroidogenesis, and recently several genes have been identified to be regulated by androgen [...] Read more.
Muscle tissue is an important target of sex steroids, and particularly, testosterone plays essential roles in muscle cell metabolism. Wide ranges of studies have reported sex differences in basal muscle steroidogenesis, and recently several genes have been identified to be regulated by androgen response elements that show innate sex differences in muscle. However, studies accounting for and demonstrating cell sexual dimorphism in vitro are still scarce and not well characterized. Here, we demonstrated the ability of 46XX and 46XY human primary skeletal muscle cells to differently activate steroidogenesis in vitro, likely related to sex-chromosome onset, and to differently induce hormone release after increasing doses of testosterone exposure. Cells were treated with testosterone at concentrations of 0.5, 2, 5, 10, 32, and 100 nmol/L for 24 h. Variations in 17β-HSD, 5α-R2, CYP-19 expression, DHT, estradiol, and androstenedione release, as well as IL6 and IL8 release, were analyzed, respectively, by RT-PCR, ELISA, and luminex-assay. Following testosterone treatments, and potentially at any concentration level, an increase in the expression of 17β-HSD, 5α-R2, and CYP-19 was observed in 46XY cells, accompanied by elevated levels of DHT, androstenedione, and IL6/IL8 release. Following the same treatment, 46XX cells exhibited an increase in 5α-R2 and CYP-19 expression, a conversion of androgens to estrogens, and a reduction in IL6 and IL8 release. In conclusion, this study demonstrated that sex-chromosome differences may influence in vitro muscle cell steroidogenesis and hormone homeostasis, which are pivotal for skeletal muscle metabolism. Full article
(This article belongs to the Special Issue New Insights into Skeletal Muscle Metabolism in Pathological and Physiological Conditions)
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