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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 3994

Special Issue Editor

Dr. Cristina Antinozzi

E-Mail Website
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.

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Keywords

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

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Published Papers (4 papers)

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Research

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 253
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 303
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 1050
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
Viewed by 1679
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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