Lack of myostatin alters intermyofibrillar mitochondria activity, unbalances redox status, and impairs tolerance to chronic repetitive contractions in muscle

Ploquin, Claire; Chabi, Béatrice; Fouret, Gilles; Vernus, Barbara; Feillet‐Coudray, Christine; Coudray, Charles; Bonnieu, Anne; Ramonatxo, Christelle

doi:10.1152/ajpendo.00652.2011

Cited by 50 publications

(51 citation statements)

References 60 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, we showed that Mstn gene deletion results in reduced lipolytic machinery in Mstn deficient hypertrophic muscles (impaired mitochondrial yield, CS and β-HAD activities and Cpt1 and Ppar- gene expressions), in line with previous studies showing that oxidative metabolism is diminished in several models of Mstn deficiency [12,13,15,16,51]. In addition, we demonstrated that the levels of cytosolic (FABP3) and sarcolemmal lipid transporters (FATP1, FATP4) are reduced, in agreement with our previous observation showing a significant reduction of FAT/CD36 levels [16].…”

Section: Myostatin and Muscle Lipid Metabolismsupporting

confidence: 90%

“…Interestingly, our previous data highlighted metabolic perturbations exclusively in the respiration of intermyofibrillar (IMF) mitochondria from Mstn-deficient muscle [13]. In diabetes mellitus type 1, cardiolipin content is decreased in the IMF subpopulation, but not in the in the sub-sarcolemmal subpopulation [69,70].…”

Section: Accepted M Manuscriptmentioning

confidence: 94%

“…We and others have recently shown that inhibition of Mstn represses muscle endurance and metabolic mitochondrial function [13,15]. As this metabolic phenotype is greatly dependent on lipids, we first investigated whether myostatin deletion would impact mitochondrial lipid oxidation in muscle.…”

Section: Decreased Lipid Oxidation In Mstn Ko Musclementioning

confidence: 99%

“…In parallel, many other metabolic changes have been documented in Mstn KO muscle such as a decrease in mitochondrial content, disturbance in mitochondrial respiratory function with a decay in the respiratory control ratio in intermyofibrillar mitochondria, and a decline in porine activity [11,13,15]. In addition, a decrease of fatty acid translocase (FAT/CD36) level, a lipid transporter, and the citrate synthase (CS) activity, one of the main mitochondrial oxidative enzyme, associated with a lower peroxisome proliferatoractivated receptor gamma coactivator 1 alpha (PGC1-α) expression has been observed [15,16].…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, beyond muscle hypertrophy, Mstn KO mice show a disturbed muscle function with loss of muscle strength and endurance in vivo or ex vivo accompanied with a decrease in mechanical performance, and ATP production during exercise [11,12,13,14]. In parallel, many other metabolic changes have been documented in Mstn KO muscle such as a decrease in mitochondrial content, disturbance in mitochondrial respiratory function with a decay in the respiratory control ratio in intermyofibrillar mitochondria, and a decline in porine activity [11,13,15].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Myostatin deficiency is associated with lipidomic abnormalities in skeletal muscles

Baati

Feillet‐Coudray

Fouret

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

Self Cite

View full text Add to dashboard Cite

Myostatin (Mstn) deficiency leads to skeletal muscle overgrowth and Mstn inhibition is considered as a promising treatment for muscle-wasting disorders. Mstn gene deletion in mice also causes metabolic changes with decreased mitochondria content, disturbance in mitochondrial respiratory function and increased muscle fatigability. However the impact of MSTN deficiency on these metabolic changes is not fully elucidated. Here, we hypothesized that lack of MSTN will alter skeletal muscle membrane lipid composition in relation with pronounced alterations in muscle function and metabolism. Indeed, phospholipids and in particular cardiolipin mostly present in the inner mitochondrial membrane, play a crucial role in mitochondria function and oxidative phosphorylation process. We observed that Mstn KO muscle had reduced fat membrane transporter levels (FAT/CD36, FABP3, FATP1 and FATP4) associated with decreased lipid oxidative pathway (citrate synthase and β-HAD activities) and impaired lipogenesis (decreased triglyceride and free fatty acid content), indicating a role of mstn in muscle lipid metabolism. We further analyzed phospholipid classes and fatty acid composition by chromatographic methods in muscle and mitochondrial membranes. Mstn KO mice showed increased levels of saturated and polyunsaturated fatty acids at the expense of monounsaturated fatty acids. We also demonstrated, in this phenotype, a reduction in cardiolipin proportion in mitochondrial membrane versus the proportion of others phospholipids, in relation with a decrease in the expression of phosphatidylglycerolphosphate synthase and cardiolipin synthase, enzymes involved in cardiolipin synthesis. These data illustrate the importance of lipids as a link by which MSTN deficiency can impact mitochondrial bioenergetics in skeletal muscle. (Résumé d'auteur

show abstract

Section: Myostatin and Muscle Lipid Metabolismsupporting

confidence: 90%

Section: Accepted M Manuscriptmentioning

confidence: 94%

Section: Decreased Lipid Oxidation In Mstn Ko Musclementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Myostatin deficiency is associated with lipidomic abnormalities in skeletal muscles

Baati

Feillet‐Coudray

Fouret

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

Self Cite

View full text Add to dashboard Cite

show abstract

Myokines: A central point in managing redox homeostasis and quality of life

Rathor,

Suryakumar

2024

BioFactors

View full text Add to dashboard Cite

Redox homeostasis is a crucial phenomenon that is obligatory for maintaining the healthy status of cells. However, the loss of redox homeostasis may lead to numerous diseases that ultimately result in a compromised quality of life. Skeletal muscle is an endocrine organ that secretes hundreds of myokines. Myokines are peptides and cytokines produced and released by muscle fibers. Skeletal muscle secreted myokines act as a robust modulator for regulating cellular metabolism and redox homeostasis which play a prime role in managing and improving metabolic function in multiple organs. Further, the secretory myokines maintain redox homeostasis not only in muscles but also in other organs of the body via stabilizing oxidants and antioxidant levels. Myokines are also engaged in maintaining mitochondrial dynamics as mitochondria is a central point for the generation of reactive oxygen species (ROS). Ergo, myokines also act as a central player in communicating signals to other organs, including the pancreas, gut, liver, bone, adipose tissue, brain, and skin via their autocrine, paracrine, or endocrine effects. The present review provides a comprehensive overview of skeletal muscle‐secreted myokines in managing redox homeostasis and quality of life. Additionally, probable strategies will be discussed that provide a solution for a better quality of life.

show abstract

Myostatin inhibition in combination with antisense oligonucleotide therapy improves outcomes in spinal muscular atrophy

Zhou

Meng

Malerba

et al. 2020

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

Background Spinal muscular atrophy (SMA) is caused by genetic defects in the survival motor neuron 1 (SMN1) gene that lead to SMN deficiency. Different SMN‐restoring therapies substantially prolong survival and function in transgenic mice of SMA. However, these therapies do not entirely prevent muscle atrophy and restore function completely. To further improve the outcome, we explored the potential of a combinatorial therapy by modulating SMN production and muscle‐enhancing approach as a novel therapeutic strategy for SMA. Methods The experiments were performed in a mouse model of severe SMA. A previously reported 25‐mer morpholino antisense oligomer PMO25 was used to restore SMN expression. The adeno‐associated virus‐mediated expression of myostatin propeptide was used to block the myostatin pathway. Newborn SMA mice were treated with a single subcutaneous injection of 40 μg/g (therapeutic dose) or 10 μg/g (low‐dose) PMO25 on its own or together with systemic delivery of a single dose of adeno‐associated virus‐mediated expression of myostatin propeptide. The multiple effects of myostatin inhibition on survival, skeletal muscle phenotype, motor function, neuromuscular junction maturation, and proprioceptive afferences were evaluated. Results We show that myostatin inhibition acts synergistically with SMN‐restoring antisense therapy in SMA mice treated with the higher therapeutic dose PMO25 (40 μg/g), by increasing not only body weight (21% increase in male mice at Day 40), muscle mass (38% increase), and fibre size (35% increase in tibialis anterior muscle in 3 month female SMA mice), but also motor function and physical performance as measured in hanging wire test (two‐fold increase in time score) and treadmill exercise test (two‐fold increase in running distance). In SMA mice treated with low‐dose PMO25 (10 μg/g), the early application of myostatin inhibition prolongs survival (40% increase), improves neuromuscular junction maturation (50% increase) and innervation (30% increase), and increases both the size of sensory neurons in dorsal root ganglia (60% increase) and the preservation of proprioceptive synapses in the spinal cord (30% increase). Conclusions These data suggest that myostatin inhibition, in addition to the well‐known effect on muscle mass, can also positively influence the sensory neural circuits that may enhance motor neurons function. While the availability of the antisense drug Spinraza for SMA and other SMN‐enhancing therapies has provided unprecedented improvement in SMA patients, there are still unmet needs in these patients. Our study provides further rationale for considering myostatin inhibitors as a therapeutic intervention in SMA patients, in combination with SMN‐restoring drugs.

show abstract

Lack of myostatin alters intermyofibrillar mitochondria activity, unbalances redox status, and impairs tolerance to chronic repetitive contractions in muscle

Cited by 50 publications

References 60 publications

Myostatin deficiency is associated with lipidomic abnormalities in skeletal muscles

Myostatin deficiency is associated with lipidomic abnormalities in skeletal muscles

Myokines: A central point in managing redox homeostasis and quality of life

Myostatin inhibition in combination with antisense oligonucleotide therapy improves outcomes in spinal muscular atrophy

Contact Info

Product

Resources

About