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Start Over Author "Laura Cussonneau" Topic muscle atrophy
4 results on '"Laura Cussonneau"'

1. Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear

Author

Laura Cussonneau, Christian Boyer, Charlotte Brun, Christiane Deval, Emmanuelle Loizon, Emmanuelle Meugnier, Elise Gueret, Emeric Dubois, Daniel Taillandier, Cécile Polge, Daniel Béchet, Guillemette Gauquelin-Koch, Alina L. Evans, Jon M. Arnemo, Jon E. Swenson, Stéphane Blanc, Chantal Simon, Etienne Lefai, Fabrice Bertile, and Lydie Combaret

Subjects
brown bear hibernation, mouse unloading, muscle atrophy, physical inactivity, RNA sequencing, TGF-β/BMP signaling, Cytology, QH573-671
Abstract

Muscle atrophy arises from a multiplicity of physio-pathological situations and has very detrimental consequences for the whole body. Although knowledge of muscle atrophy mechanisms keeps growing, there is still no proven treatment to date. This study aimed at identifying new drivers for muscle atrophy resistance. We selected an innovative approach that compares muscle transcriptome between an original model of natural resistance to muscle atrophy, the hibernating brown bear, and a classical model of induced atrophy, the unloaded mouse. Using RNA sequencing, we identified 4415 differentially expressed genes, including 1746 up- and 2369 down-regulated genes, in bear muscles between the active versus hibernating period. We focused on the Transforming Growth Factor (TGF)-β and the Bone Morphogenetic Protein (BMP) pathways, respectively, involved in muscle mass loss and maintenance. TGF-β- and BMP-related genes were overall down- and up-regulated in the non-atrophied muscles of the hibernating bear, respectively, and the opposite occurred for the atrophied muscles of the unloaded mouse. This was further substantiated at the protein level. Our data suggest TGF-β/BMP balance is crucial for muscle mass maintenance during long-term physical inactivity in the hibernating bear. Thus, concurrent activation of the BMP pathway may potentiate TGF-β inhibiting therapies already targeted to prevent muscle atrophy.

Published
2021
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2. Induction of ATF4-Regulated Atrogenes Is Uncoupled from Muscle Atrophy during Disuse in Halofuginone-Treated Mice and in Hibernating Brown Bears

Author

Laura Cussonneau, Cécile Coudy-Gandilhon, Christiane Deval, Ghita Chaouki, Mehdi Djelloul-Mazouz, Yoann Delorme, Julien Hermet, Guillemette Gauquelin-Koch, Cécile Polge, Daniel Taillandier, Julien Averous, Alain Bruhat, Céline Jousse, Isabelle Papet, Fabrice Bertile, Etienne Lefai, Pierre Fafournoux, Anne-Catherine Maurin, Lydie Combaret, Unité de Nutrition Humaine (UNH), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)

Subjects
muscle atrophy, [SDV]Life Sciences [q-bio], Organic Chemistry, General Medicine, hibernating bear, Catalysis, Computer Science Applications, atrogenes, Inorganic Chemistry, halofuginone, TGF-beta/BMP signalling, unloading, hindlimb suspension, skeletal muscle, ATF4, TGF-β/BMP signalling, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy
Abstract

Activating transcription factor 4 (ATF4) is involved in muscle atrophy through the overexpression of some atrogenes. However, it also controls the transcription of genes involved in muscle homeostasis maintenance. Here, we explored the effect of ATF4 activation by the pharmacological molecule halofuginone during hindlimb suspension (HS)-induced muscle atrophy. Firstly, we reported that periodic activation of ATF4-regulated atrogenes (Gadd45a, Cdkn1a, and Eif4ebp1) by halofuginone was not associated with muscle atrophy in healthy mice. Secondly, halofuginone-treated mice even showed reduced atrophy during HS, although the induction of the ATF4 pathway was identical to that in untreated HS mice. We further showed that halofuginone inhibited transforming growth factor-β (TGF-β) signalling, while promoting bone morphogenetic protein (BMP) signalling in healthy mice and slightly preserved protein synthesis during HS. Finally, ATF4-regulated atrogenes were also induced in the atrophy-resistant muscles of hibernating brown bears, in which we previously also reported concurrent TGF-β inhibition and BMP activation. Overall, we show that ATF4-induced atrogenes can be uncoupled from muscle atrophy. In addition, our data also indicate that halofuginone can control the TGF-β/BMP balance towards muscle mass maintenance. Whether halofuginone-induced BMP signalling can counteract the effect of ATF4-induced atrogenes needs to be further investigated and may open a new avenue to fight muscle atrophy. Finally, our study opens the way for further studies to identify well-tolerated chemical compounds in humans that are able to fine-tune the TGF-β/BMP balance and could be used to preserve muscle mass during catabolic situations.

Published
2022
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3. Concurrent BMP signalling maintenance and TGF-β signalling inhibition is a hallmark of natural resistance to muscle atrophy in the hibernating bear

Author

Elise Gueret, Stéphane Blanc, Emmanuelle Meugnier, Etienne Lefai, Cécile Polge, Chantal Simon, Guillemette Gauquelin-Koch, Charlotte Brun, Laura Cussonneau, Alina L. Evans, Fabrice Bertile, Daniel Béchet, Jon M. Arnemo, Christian Boyer, Lydie Combaret, Daniel Taillandier, Christiane Deval, Emmanuelle Loizon, Jon E. Swenson, Emeric Dubois, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Université Côte d'Azur - Faculté de Médecine (UCA Faculté Médecine), Université Côte d'Azur (UCA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre National d’Études Spatiales [Paris] (CNES), Inland Norway University of Applied Sciences - Høgskolen i Innlandet, Norwegian University of Life Sciences (NMBU), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Male, muscle atrophy, Time Factors, [SDV]Life Sciences [q-bio], Quadriceps Muscle, Transcriptome, Mice, 0302 clinical medicine, Transforming Growth Factor beta, Hibernation, Gene Regulatory Networks, RNA-Seq, Biology (General), mouse unloading, RNA sequencing, General Medicine, TGF-/BMP signaling, Muscle atrophy, TGF-β/BMP signaling, Cell biology, Muscular Atrophy, Hindlimb Suspension, Bone Morphogenetic Proteins, Female, medicine.symptom, brown bear hibernation, Ursidae, Signal Transduction, QH301-705.5, Period (gene), [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Bone morphogenetic protein, Article, 03 medical and health sciences, Atrophy, medicine, Animals, Gene, Gene Expression Profiling, RNA, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Gene Expression Regulation, physical inactivity, 030217 neurology & neurosurgery, Transforming growth factor
Abstract

International audience; Muscle atrophy arises from a multiplicity of physio-pathological situations and has very detrimental consequences for the whole body. Although knowledge of muscle atrophy mechanisms keeps growing, there is still no proven treatment to date. This study aimed at identifying new drivers for muscle atrophy resistance. We selected an innovative approach that compares muscle transcriptome between an original model of natural resistance to muscle atrophy, the hibernating brown bear, and a classical model of induced atrophy, the unloaded mouse. Using RNA sequencing, we identified 4415 differentially expressed genes, including 1746 up- and 2369 down-regulated genes, in bear muscles between the active versus hibernating period. We focused on the Transforming Growth Factor (TGF)-β and the Bone Morphogenetic Protein (BMP) pathways, respectively, involved in muscle mass loss and maintenance. TGF-β- and BMP-related genes were overall down- and up-regulated in the non-atrophied muscles of the hibernating bear, respectively, and the opposite occurred for the atrophied muscles of the unloaded mouse. This was further substantiated at the protein level. Our data suggest TGF-β/BMP balance is crucial for muscle mass maintenance during long-term physical inactivity in the hibernating bear. Thus, concurrent activation of the BMP pathway may potentiate TGF-β inhibiting therapies already targeted to prevent muscle atrophy.

Published
2021
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4. Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control

Author

Cécile Polge, Daniel Taillandier, Laura Cussonneau, Lydie Combaret, Dulce Peris-Moreno, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), AFM/Telethon (grant #19521), from the French government IDEX-ISITE initiative 16-IDEX-0001 (CAP 20e25) and from the Fondation pour la Recherche Médicale (labelling FRM, labelling FRM, DEQ20180339180 and from CNES (Centre national d’études spatiales, and DAR 4800001057).

Subjects
[SDV]Life Sciences [q-bio], Pharmaceutical Science, Review, Analytical Chemistry, Muscle hypertrophy, 0302 clinical medicine, Ubiquitin, MAFbx, Drug Discovery, 0303 health sciences, treatment, biology, anabolism, catabolism, MuRF1, Muscle atrophy, 3. Good health, Ubiquitin ligase, Cell biology, Muscular Atrophy, medicine.anatomical_structure, E3 ubiquitin ligase, Chemistry (miscellaneous), Molecular Medicine, medicine.symptom, Signal transduction, hypertrophy, signaling, Signal Transduction, Ubiquitin-Protein Ligases, lcsh:QD241-441, 03 medical and health sciences, skeletal muscle atrophy, Atrophy, lcsh:Organic chemistry, medicine, Animals, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Physical and Theoretical Chemistry, 030304 developmental biology, therapy, Organic Chemistry, Skeletal muscle, medicine.disease, Proteasome, Protein Biosynthesis, biology.protein, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract

International audience; Skeletal muscle loss is a detrimental side-effect of numerous chronic diseases that dramatically increases mortality and morbidity. The alteration of protein homeostasis is generally due to increased protein breakdown while, protein synthesis may also be down-regulated. The ubiquitin proteasome system (UPS) is a master regulator of skeletal muscle that impacts muscle contractile properties and metabolism through multiple levers like signaling pathways, contractile apparatus degradation, etc. Among the different actors of the UPS, the E3 ubiquitin ligases specifically target key proteins for either degradation or activity modulation, thus controlling both pro-anabolic or pro-catabolic factors. The atrogenes MuRF1/TRIM63 and MAFbx/Atrogin-1 encode for key E3 ligases that target contractile proteins and key actors of protein synthesis respectively. However, several other E3 ligases are involved upstream in the atrophy program, from signal transduction control to modulation of energy balance. Controlling E3 ligases activity is thus a tempting approach for preserving muscle mass. While indirect modulation of E3 ligases may prove beneficial in some situations of muscle atrophy, some drugs directly inhibiting their activity have started to appear. This review summarizes the main signaling pathways involved in muscle atrophy and the E3 ligases implicated, but also the molecules potentially usable for future therapies.

Published
2021
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