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Metabolites
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Muscle Metabolic Response and Adaptation to Exercise, Diet, and Environment
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Muscle Metabolic Response and Adaptation to Exercise, Diet, and Environment

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Animal Metabolism".

Deadline for manuscript submissions: 30 August 2025 | Viewed by 10480

Special Issue Editor

Dr. Susumu Muroya

E-Mail Website
Guest Editor
NARO Institute of Livestock and Grassland Science, Tsukuba, Ibaraki, Japan
Interests: muscle biology; meat biochemistry; epigenetics; metabolomics; animal science

Special Issue Information

Dear Colleagues,

Skeletal muscle plays a crucial role as a locomotor organ and as a modulator of systemic energy homeostasis in animals. Dysregulation of muscle metabolism in humans leads to the development of serious diseases such as diabetes and sarcopenia. In farm animals, excessive pursuit of productivity sometimes causes disruption of energy homeostasis as exhibited in undesirable products such as abnormal chicken meat quality derived from disturbed mitophagy and/or redox metabolism. The optimized muscle metabolism is important for an increase in muscle mass during animal development and growth. Therefore, a better understanding of mechanisms underlying developmental regulation of metabolisms and adaptation of skeletal muscle metabolism to various inputs including diet, exercise, and environment stress contributes to further improvement of human health, animal welfare and productivity, and meat quality.

Recent metabolomics technologies, in combination with the development of bioinformatics and imaging mass spectrometry, has provided great benefits in the approach to unexplored muscle metabolisms. With these backgrounds, this Special Issue aims to share and discuss research topics focusing on molecular mechanisms of the metabolic response of skeletal muscle tissue and cells in the view of genes, transcripts, proteins, metabolites, and epigenetic factors, when exposed to various nutritional conditions and physiological stress-inducing environments. Papers addressing mechanisms of metabolic adaptation and disturbance, especially in terms of mitochondria, energy homeostasis, lipid metabolism, and redox metabolism, including cell culture studies, could be the desired topics in this issue. Meanwhile, other studies regarding skeletal muscle growth, maturation, aging, disease, and farm animal intramuscular fat and postmortem muscle aging are also welcome. Most of these studies may be conducted by use of metabolomics and integrative multi-omics approaches, but also cutting-edge studies targeting a specific key metabolite and inter-organ crosstalk around muscle in the above-mentioned fields are also acceptable.

Dr. Susumu Muroya
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. Metabolites 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
  • metabolomics
  • mitochondria
  • energy metabolism
  • lipid metabolism
  • nutrition
  • feeding
  • environment
  • exercise
  • stress

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Published Papers (5 papers)

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Research

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19 pages, 2140 KiB  
Article
Combined Effects of Ketogenic Diet and Aerobic Exercise on Skeletal Muscle Fiber Remodeling and Metabolic Adaptation in Simulated Microgravity Mice
by Jun Chen, Wenjiong Li, Liang Yu, Bowei Zhang, Zhili Li, Peng Zou, Bai Ding, Xiaoqian Dai and Qirong Wang
Metabolites 2025, 15(4), 270; https://doi.org/10.3390/metabo15040270 - 13 Apr 2025
Viewed by 423
Abstract
Objective: Prolonged microgravity environments impair skeletal muscle homeostasis by triggering fiber-type transitions and metabolic dysregulation. Although exercise and nutritional interventions may alleviate disuse atrophy, their synergistic effects under microgravity conditions remain poorly characterized. This study investigated the effects of an 8-week ketogenic diet [...] Read more.
Objective: Prolonged microgravity environments impair skeletal muscle homeostasis by triggering fiber-type transitions and metabolic dysregulation. Although exercise and nutritional interventions may alleviate disuse atrophy, their synergistic effects under microgravity conditions remain poorly characterized. This study investigated the effects of an 8-week ketogenic diet combined with aerobic exercise in hindlimb-unloaded mice on muscle fiber remodeling and metabolic adaptation. Methods: Seven-week-old male C57BL/6J mice were randomly divided into six groups: normal diet control (NC), normal diet with hindlimb unloading (NH), normal diet with hindlimb unloading and exercise (NHE), ketogenic diet control (KC), ketogenic diet with hindlimb unloading (KH), and ketogenic diet with hindlimb unloading and exercise (KHE). During the last two weeks of intervention, hindlimb unloading was applied to simulate microgravity. Aerobic exercise groups performed moderate-intensity treadmill running (12 m/min, 60 min/day, and 6 days/week) for 8 weeks. Body weight, blood ketone, and glucose levels were measured weekly. Post-intervention assessments included the respiratory exchange ratio (RER), exhaustive exercise performance tests, and biochemical analyses of blood metabolic parameters. The skeletal muscle fiber-type composition was evaluated via immunofluorescence staining, lipid deposition was assessed using Oil Red O staining, glycogen content was analyzed by Periodic Acid–Schiff (PAS) staining, and gene expression was quantified using quantitative real-time PCR (RT-qPCR). Results: Hindlimb unloading significantly decreased body weight, induced muscle atrophy, and reduced exercise endurance in mice. However, the combination of KD and aerobic exercise significantly attenuated these adverse effects, as evidenced by increased proportions of oxidative muscle fibers (MyHC-I) and decreased proportions of glycolytic fibers (MyHC-IIb). Additionally, this combined intervention upregulated the expression of lipid metabolism-associated genes, including CPT-1b, HADH, PGC-1α, and FGF21, enhancing lipid metabolism and ketone utilization. These metabolic adaptations corresponded with improved exercise performance, demonstrated by the increased time to exhaustion in the KHE group compared to other hindlimb unloading groups. Conclusions: The combination of a ketogenic diet and aerobic exercise effectively ameliorates simulated microgravity-induced skeletal muscle atrophy and endurance impairment, primarily by promoting a fiber-type transition from MyHC-IIb to MyHC-I and enhancing lipid metabolism gene expression (CPT-1b, HADH, and PGC-1α). These findings underscore the potential therapeutic value of combined dietary and exercise interventions for mitigating muscle atrophy under simulated microgravity conditions. Full article
(This article belongs to the Special Issue Muscle Metabolic Response and Adaptation to Exercise, Diet, and Environment)
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19 pages, 2607 KiB  
Article
Temperament Upregulates Mitochondrial Enzymes and Negatively Affects Myofibrillar Fragmentation in Beef of Excitable Bos taurus indicus Cattle
by Patricia Maloso Ramos, Eduardo Francisquine Delgado, Ana Cláudia da Silva, Nara Regina Brandão Cônsolo, Vinicius Laerte Silva Herreira, João Marcos Bovetto de Campos Valim, Fernanda Maria Marins Ocampos, Luiz Alberto Colnago and Saulo da Luz e Silva
Metabolites 2025, 15(1), 24; https://doi.org/10.3390/metabo15010024 - 7 Jan 2025
Viewed by 692
Abstract
Background: Bos taurus indicus cattle is known to be temperamental and to produce beef with greater variability in terms of quality compared to beef of Bos taurus taurus. Cattle adaptability and resilience are of great importance to sustain beef production worldwide. Objective: [...] Read more.
Background: Bos taurus indicus cattle is known to be temperamental and to produce beef with greater variability in terms of quality compared to beef of Bos taurus taurus. Cattle adaptability and resilience are of great importance to sustain beef production worldwide. Objective: The study aimed to understand early post-mortem metabolites among muscles with different fiber types profile of calm and excitable Nellore, as well as its relationship with fragmentation of beef aged up to 28 d. Methods: Animals were evaluated based on chute score and exit velocity to calculate a temperament index, which was used to classify them as calm or excitable. At slaughter, the pH and temperature declines of Triceps brachii (TB) and Longissimus lumborum (LL) were measured, muscles were sampled, and aged up to 28 d. Metabolites were determined, and sarcomere length and myofibrillar fragmentation index (MFI) were quantified. Metabolomics data were analyzed using a multivariate approach, while other traits were investigated through ANOVA. Results: The pH decline was affected by all three fixed effects investigated (temperament × muscle × time post-mortem: p = 0.016), while temperature decline was affected by muscle × time (p < 0.001). Metabolites differed among muscles and cattle temperament, with excitable cattle showing greater taurine abundance in LL, as well as greater creatine in TB 1 h post-mortem, based on the volcano plot. Sarcomere length and MFI results revealed faster and limited tenderization in excitable cattle beef. Conclusions: Altogether, results emphasized the upregulation of mitochondrial enzymes and reduced tenderization as determinants of inferior beef quality after prolonged aging in excitable cattle. Full article
(This article belongs to the Special Issue Muscle Metabolic Response and Adaptation to Exercise, Diet, and Environment)
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18 pages, 5035 KiB  
Article
Depth of Interbreed Difference in Postmortem Bovine Muscle Determined by CE-FT/MS and LC-FT/MS Metabolomics
by Susumu Muroya, Yuta Horiuchi, Kazuki Iguchi, Takuma Higuchi, Shuji Sakamoto, Koichi Ojima and Kazutsugu Matsukawa
Metabolites 2024, 14(5), 261; https://doi.org/10.3390/metabo14050261 - 1 May 2024
Cited by 1 | Viewed by 2173
Abstract
Japanese Brown (JBR) cattle have moderately marbled beef compared to the highly marbled beef of Japanese Black (JBL) cattle; however, their skeletal muscle properties remain poorly characterized. To unveil interbreed metabolic differences over the previous results, we explored the metabolome network changes before [...] Read more.
Japanese Brown (JBR) cattle have moderately marbled beef compared to the highly marbled beef of Japanese Black (JBL) cattle; however, their skeletal muscle properties remain poorly characterized. To unveil interbreed metabolic differences over the previous results, we explored the metabolome network changes before and after postmortem 7-day aging in the trapezius muscle of the two cattle breeds by employing a deep and high-coverage metabolomics approach. Using both capillary electrophoresis (CE) and ultra-high-performance liquid chromatography (UHPLC)–Fourier transform mass spectrometry (FT/MS), we detected 522 and 384 annotated peaks, respectively, across all muscle samples. The CE-based results showed that the cattle were clearly separated by breed and postmortem age in multivariate analyses. The metabolism related to glutathione, glycolysis, vitamin K, taurine, and arachidonic acid was enriched with differentially abundant metabolites in aged muscles, in addition to amino acid (AA) metabolisms. The LC-based results showed that the levels of bile-acid-related metabolites, such as tauroursodeoxycholic acid (TUDCA), were high in fresh JBR muscle and that acylcarnitines were enriched in aged JBR muscle, compared to JBL muscle. Postmortem aging resulted in an increase in fatty acids and a decrease in acylcarnitine in the muscles of both cattle breeds. In addition, metabolite set enrichment analysis revealed that JBR muscle was distinctive in metabolisms related to pyruvate, glycerolipid, cardiolipin, and mitochondrial energy production, whereas the metabolisms related to phosphatidylethanolamine, nucleotide triphosphate, and AAs were characteristic of JBL. This suggests that the interbreed differences in postmortem trapezius muscle are associated with carnitine/acylcarnitine transport, β-oxidation, tricarboxylic acid cycle, and mitochondrial membrane stability, in addition to energy substrate and AA metabolisms. These interbreed differences may characterize beef quality traits such as the flavor intensity and oxidative stability. Full article
(This article belongs to the Special Issue Muscle Metabolic Response and Adaptation to Exercise, Diet, and Environment)
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15 pages, 3475 KiB  
Article
Moderate Effects of Hypoxic Training at Low and Supramaximal Intensities on Skeletal Muscle Metabolic Gene Expression in Mice
by Svitlana Drozdovska, Nadège Zanou, Jessica Lavier, Lucia Mazzolai, Grégoire P. Millet and Maxime Pellegrin
Metabolites 2023, 13(10), 1103; https://doi.org/10.3390/metabo13101103 - 21 Oct 2023
Cited by 1 | Viewed by 4197
Abstract
The muscle molecular adaptations to different exercise intensities in combination with hypoxia are not well understood. This study investigated the effect of low- and supramaximal-intensity hypoxic training on muscle metabolic gene expression in mice. C57BL/6 mice were divided into two groups: sedentary and [...] Read more.
The muscle molecular adaptations to different exercise intensities in combination with hypoxia are not well understood. This study investigated the effect of low- and supramaximal-intensity hypoxic training on muscle metabolic gene expression in mice. C57BL/6 mice were divided into two groups: sedentary and training. Training consisted of 4 weeks at low or supramaximal intensity, either in normoxia or hypoxia (FiO2 = 0.13). The expression levels of genes involved in the hypoxia signaling pathway (Hif1a and Vegfa), the metabolism of glucose (Gys1, Glut4, Hk2, Pfk, and Pkm1), lactate (Ldha, Mct1, Mct4, Pdh, and Pdk4) and lipid (Cd36, Fabp3, Ucp2, Hsl, and Mcad), and mitochondrial energy metabolism and biogenesis (mtNd1, mtNd6, CytC, CytB, Pgc1a, Pgc1β, Nrf1, Tfam, and Cs) were determined in the gastrocnemius muscle. No physical performance improvement was observed between groups. In normoxia, supramaximal intensity training caused upregulation of major genes involved in the transport of glucose and lactate, fatty acid oxidation, and mitochondrial biogenesis, while low intensity training had a minor effect. The exposure to hypoxia changed the expression of some genes in the sedentary mice but had a moderate effect in trained mice compared to respective normoxic mice. In hypoxic groups, low-intensity training increased the mRNA levels of Mcad and Cs, while supramaximal intensity training decreased the mRNA levels of Mct1 and Mct4. The results indicate that hypoxic training, regardless of exercise intensity, has a moderate effect on muscle metabolic gene expression in healthy mice. Full article
(This article belongs to the Special Issue Muscle Metabolic Response and Adaptation to Exercise, Diet, and Environment)
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Review

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21 pages, 1534 KiB  
Review
Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis
by Jiayin Wang, Dandan Jia, Zhiwang Zhang and Dan Wang
Metabolites 2025, 15(1), 59; https://doi.org/10.3390/metabo15010059 - 16 Jan 2025
Cited by 1 | Viewed by 1902
Abstract
Background/Objectives: Sarcopenia, characterized by the progressive loss of muscle mass and strength, is linked to physical disability, metabolic dysfunction, and an increased risk of mortality. Exercise therapy is currently acknowledged as a viable approach for addressing sarcopenia. Nevertheless, the molecular mechanisms behind [...] Read more.
Background/Objectives: Sarcopenia, characterized by the progressive loss of muscle mass and strength, is linked to physical disability, metabolic dysfunction, and an increased risk of mortality. Exercise therapy is currently acknowledged as a viable approach for addressing sarcopenia. Nevertheless, the molecular mechanisms behind exercise training or physical activity remain poorly understood. The disruption of mitochondrial homeostasis is implicated in the pathogenesis of sarcopenia. Exercise training effectively delays the onset of sarcopenia by significantly maintaining mitochondrial homeostasis, including promoting mitophagy, improving mitochondrial biogenesis, balancing mitochondrial dynamics, and maintaining mitochondrial redox. Exerkines (e.g., adipokines, myokines, hepatokines, and osteokines), signaling molecules released in response to exercise training, may potentially contribute to skeletal muscle metabolism through ameliorating mitochondrial homeostasis, reducing inflammation, and regulating protein synthesis as a defense against sarcopenia. Methods: In this review, we provide a detailed summary of exercise-induced exerkines and confer their benefit, with particular focus on their impact on mitochondrial homeostasis in the context of sarcopenia. Results: Exercise induces substantial adaptations in skeletal muscle, including increased muscle mass, improved muscle regeneration and hypertrophy, elevated hormone release, and enhanced mitochondrial function. An expanding body of research highlights that exerkines have the potential to regulate processes such as mitophagy, mitochondrial biogenesis, dynamics, autophagy, and redox balance. These mechanisms contribute to the maintenance of mitochondrial homeostasis, thereby supporting skeletal muscle metabolism and mitochondrial health. Conclusions: Through a comprehensive investigation of the molecular mechanisms within mitochondria, the context reveals new insights into the potential of exerkines as key exercise-protective sensors for combating sarcopenia. Full article
(This article belongs to the Special Issue Muscle Metabolic Response and Adaptation to Exercise, Diet, and Environment)
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