Coordinated regulation of skeletal muscle mass and metabolic plasticity during recovery from disuse

Kneppers, Anita; Leermakers, Pieter A.; Pansters, N.A.M.; Backx, Evelien; Gosker, Harry R.; Loon, Luc J. C. van; Schols, A.M.W.J.; Langen, Ramon; Verdijk, Lex B.

doi:10.1096/fj.201701403rrr

Cited by 9 publications

(3 citation statements)

References 86 publications

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“…Specifically, we find 4–10‐fold greater Bnip3 in female mice unloaded for 24–48 h compared with male mice whom had marginal differences in Bnip3 between unloading conditions. Many prior works have found increases in BNIP3 during the early phases of muscle atrophy, 32–34 which then appears to reverse to decreased BNIP3 with prolonged durations (>2 weeks) of disuse 27 . Yet to our knowledge, no study has included markers of mitophagy/autophagy content in both male and female rodents during these early phases of disuse.…”

Section: Discussionmentioning

confidence: 95%

Mitochondrial aberrations during the progression of disuse atrophy differentially affect male and female mice

Rosa‐Caldwell

Lim

Haynie

et al. 2021

J cachexia sarcopenia muscle

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Background Disuse decreases muscle size and is predictive of mortality across multiple pathologies. Detriments to mitochondrial function are hypothesized to underlie disuse‐induced muscle atrophy. Little data exist on early mechanisms contributing to onset of these pathologies, nor is it known how they differ between sexes. The purpose of this study was to examine differential and conserved responses to mitochondrial quality control in male and female mice during the development and progression of disuse‐induced atrophy. Methods One hundred C57BL/6J mice (50 male and 50 female) were hindlimb unloaded to induce disuse atrophy for 0 (con), 24, 48, 72, or 168 h. At designated time‐points, extensor digitorum longus, gastrocnemius, and soleus muscles were collected for analysis of mitochondrial quality control markers. Results One hundred sixty‐eight hours of disuse resulted in ~25% lower oxidative muscle fibre CSA in both male (P = 0.003) and female (P = 0.02) mice without any differences due to disuse in glycolytic fibres. In male mice, 48 h of unloading was sufficient to result in ~67% greater mitochondrial oxidative stress as assessed by the reporter gene pMitoTimer compared with 0 h (P = 0.002), this mitochondrial stress preceded detectable muscle loss. However in female mice, mitochondrial oxidative stress did not occur until 168 h of disuse (~40% greater mitochondrial oxidative stress in 168 h compared with 0 h of disuse, P < 0.0001). Blunted oxidative stress in female mice appeared to coincide with greater inductions of autophagy and mitophagy in female mice (~3‐fold greater BNIP3 and ~6‐fold greater LC3II/I ratio P < 0.0001 and P = 0.038 respectively). Male mice overall had greater reactive oxygen species (ROS) production compared with female mice. Female mice had a greater induction of ROS within 24 h of disuse (~4‐fold greater compared with 0 h, P < 0.0001); whereas male mice did not have greater ROS production until 168 h of disuse (~2‐fold greater, P < 0.0001). Although all muscle types exhibited some alterations to mitochondrial quality control, such as increased markers of mitophagy and fission, the soleus muscle in both male and female mice exhibited consistent alterations to various markers of mitochondrial quality. Markers of mitochondrial translation were approximately 30–50% lower within 24 h of unloading in both male and female soleus muscle (P value ranges: <0.0001–0.03). Conclusions Disuse negatively affects mitochondria differentially between sexes during development of muscle wasting. Acutely, female mice may forgo muscle mass to maintain mitochondrial quality compared with male mice. These differences may contribute to divergent clinical manifestations of atrophy.

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Section: Discussionmentioning

confidence: 95%

Mitochondrial aberrations during the progression of disuse atrophy differentially affect male and female mice

Rosa‐Caldwell

Lim

Haynie

et al. 2021

J cachexia sarcopenia muscle

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“…The decrease in muscle protein synthesis caused by disuse muscle atrophy leads to the reduction in muscle mass and strength. However, this can be restored through physical activity and maintaining an active lifestyle, especially in younger individuals (27,28).…”

Section: Epidemiology and Clinical Presentation Comparisonmentioning

confidence: 99%

Type 2 diabetes mellitus related sarcopenia: a type of muscle loss distinct from sarcopenia and disuse muscle atrophy

Liu,

Guo,

Zheng

2024

Front. Endocrinol.

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Muscle loss is a significant health concern, particularly with the increasing trend of population aging, and sarcopenia has emerged as a common pathological process of muscle loss in the elderly. Currently, there has been significant progress in the research on sarcopenia, including in-depth analysis of the mechanisms underlying sarcopenia caused by aging and the development of corresponding diagnostic criteria, forming a relatively complete system. However, as research on sarcopenia progresses, the concept of secondary sarcopenia has also been proposed. Due to the incomplete understanding of muscle loss caused by chronic diseases, there are various limitations in epidemiological, basic, and clinical research. As a result, a comprehensive concept and diagnostic system have not yet been established, which greatly hinders the prevention and treatment of the disease. This review focuses on Type 2 Diabetes Mellitus (T2DM)-related sarcopenia, comparing its similarities and differences with sarcopenia and disuse muscle atrophy. The review show significant differences between the three muscle-related issues in terms of pathological changes, epidemiology and clinical manifestations, etiology, and preventive and therapeutic strategies. Unlike sarcopenia, T2DM-related sarcopenia is characterized by a reduction in type I fibers, and it differs from disuse muscle atrophy as well. The mechanism involving insulin resistance, inflammatory status, and oxidative stress remains unclear. Therefore, future research should further explore the etiology, disease progression, and prognosis of T2DM-related sarcopenia, and develop targeted diagnostic criteria and effective preventive and therapeutic strategies to better address the muscle-related issues faced by T2DM patients and improve their quality of life and overall health.

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“…Skeletal muscle can modify its phenotype to adapt to different external stimuli, such as disuse (Goldspink et al, 1986;Kneppers et al, 2019), hypoxia (Baresic et al, 2014;Nguyen et al, 2016), physical exercise (Yan et al, 2012;Joseph et al, 2016), among others (Gundersen, 2011), in a process known as muscle plasticity. According to this, different muscles of the body differ in their phenotype depending on the function they perform, expressing different isoforms of contractile proteins and metabolic enzymes.…”

Section: Introductionmentioning

confidence: 99%

Changes in Gene Expression of the MCU Complex Are Induced by Electrical Stimulation in Adult Skeletal Muscle

et al. 2021

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The slow calcium transient triggered by low-frequency electrical stimulation (ES) in adult muscle fibers and regulated by the extracellular ATP/IP3/IP3R pathway has been related to muscle plasticity. A regulation of muscular tropism associated with the MCU has also been described. However, the role of transient cytosolic calcium signals and signaling pathways related to muscle plasticity over the regulation of gene expression of the MCU complex (MCU, MICU1, MICU2, and EMRE) in adult skeletal muscle is completely unknown. In the present work, we show that 270 0.3-ms-long pulses at 20-Hz ES (and not at 90 Hz) transiently decreased the mRNA levels of the MCU complex in mice flexor digitorum brevis isolated muscle fibers. Importantly, when ATP released after 20-Hz ES is hydrolyzed by the enzyme apyrase, the repressor effect of 20 Hz on mRNA levels of the MCU complex is lost. Accordingly, the exposure of muscle fibers to 30 μM exogenous ATP produces the same effect as 20-Hz ES. Moreover, the use of apyrase in resting conditions (without ES) increased mRNA levels of MCU, pointing out the importance of extracellular ATP concentration over MCU mRNA levels. The use of xestospongin B (inhibitor of IP3 receptors) also prevented the decrease of mRNA levels of MCU, MICU1, MICU2, and EMRE mediated by a low-frequency ES. Our results show that the MCU complex can be regulated by electrical stimuli in a frequency-dependent manner. The changes observed in mRNA levels may be related to changes in the mitochondria, associated with the phenotypic transition from a fast- to a slow-type muscle, according to the described effect of this stimulation frequency on muscle phenotype. The decrease in mRNA levels of the MCU complex by exogenous ATP and the increase in MCU levels when basal ATP is reduced with the enzyme apyrase indicate that extracellular ATP may be a regulator of the MCU complex. Moreover, our results suggest that this regulation is part of the axes linking low-frequency stimulation with ATP/IP3/IP3R.

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Coordinated regulation of skeletal muscle mass and metabolic plasticity during recovery from disuse

Cited by 9 publications

References 86 publications

Mitochondrial aberrations during the progression of disuse atrophy differentially affect male and female mice

Mitochondrial aberrations during the progression of disuse atrophy differentially affect male and female mice

Type 2 diabetes mellitus related sarcopenia: a type of muscle loss distinct from sarcopenia and disuse muscle atrophy

Changes in Gene Expression of the MCU Complex Are Induced by Electrical Stimulation in Adult Skeletal Muscle

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