Brown Adipose Tissue undergoes pathological perturbations and shapes C2C12 myoblast homeostasis in the SOD1-G93A mouse model of Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the selective loss of motor neurons. The contribution of peripheral organs remains incompletely understood. We focused our attention on brown adipose tissue (BAT) and its secreted extracellular vesicles (...
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Elsevier
2025-02-01
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| Series: | Heliyon |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844025001811 |
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| author | Marco Rosina Silvia Scaricamazza Flaminia Riggio Gianmarco Fenili Flavia Giannessi Alessandro Matteocci Valentina Nesci Illari Salvatori Daniela F. Angelini Katia Aquilano Valerio Chiurchiù Daniele Lettieri Barbato Nicola Biagio Mercuri Cristiana Valle Alberto Ferri |
| author_facet | Marco Rosina Silvia Scaricamazza Flaminia Riggio Gianmarco Fenili Flavia Giannessi Alessandro Matteocci Valentina Nesci Illari Salvatori Daniela F. Angelini Katia Aquilano Valerio Chiurchiù Daniele Lettieri Barbato Nicola Biagio Mercuri Cristiana Valle Alberto Ferri |
| author_sort | Marco Rosina |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the selective loss of motor neurons. The contribution of peripheral organs remains incompletely understood. We focused our attention on brown adipose tissue (BAT) and its secreted extracellular vesicles (EVs) given their role in regulating systemic energy balance. In this study, we employed a multi-omics approach, including RNA sequencing (GEO identifier GSE273052) and proteomics (ProteomeXchange identifier PXD054147), to investigate the alterations in BAT and its EVs in the SOD1-G93A mouse model of ALS. Our results revealed consistent changes in the proteomic and transcriptomic profiles of BAT from SOD1-G93A mice, highlighting alterations such as mitochondrial dysfunction and impaired differentiation capacity. Specifically, primary brown adipocytes (PBAs) from SOD1-G93A mice exhibited differentiation impairment, respiratory defects, and alterations in mitochondrial dynamics. Furthermore, the BAT-derived EVs from SOD1-G93A mice displayed distinct changes in size distribution and cargo content. In parallel, such EVs negatively impacted the differentiation and homeostasis of C2C12 murine myoblasts, as well as induced atrophy in C2C12-derived myotubes. These findings suggest that BAT undergoes pathological perturbations in ALS mouse model and could impact on skeletal muscle homeostasis through the secretion of dysfunctional EVs. |
| format | Article |
| id | doaj-art-a85acd88892349cd9493538d62f931b7 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-a85acd88892349cd9493538d62f931b72025-01-26T05:04:14ZengElsevierHeliyon2405-84402025-02-01113e41801Brown Adipose Tissue undergoes pathological perturbations and shapes C2C12 myoblast homeostasis in the SOD1-G93A mouse model of Amyotrophic Lateral SclerosisMarco Rosina0Silvia Scaricamazza1Flaminia Riggio2Gianmarco Fenili3Flavia Giannessi4Alessandro Matteocci5Valentina Nesci6Illari Salvatori7Daniela F. Angelini8Katia Aquilano9Valerio Chiurchiù10Daniele Lettieri Barbato11Nicola Biagio Mercuri12Cristiana Valle13Alberto Ferri14Unit of Neurology, Fondazione PTV Policlinico Tor Vergata, Viale Oxford 81, 00133, Rome, Italy; Laboratory of Neurochemistry, IRCCS Fondazione Santa Lucia, Via del fosso di fiorano 64, 00143, Rome, Italy; Corresponding author. Unit of Neurology, Fondazione PTV Policlinico Tor Vergata, Viale Oxford 81, 00133, Rome, Italy.Laboratory of Neurochemistry, IRCCS Fondazione Santa Lucia, Via del fosso di fiorano 64, 00143, Rome, Italy; Institute of Translational Pharmacology, National Research Council, Via del fosso del cavaliere 100, 00133, Rome, ItalyDepartment of Biology and Biotechnology “Charles Darwin”, University of Roma “La Sapienza”, 00161, Rome, ItalyLaboratory of Neurochemistry, IRCCS Fondazione Santa Lucia, Via del fosso di fiorano 64, 00143, Rome, Italy; Department of Movement, Human and Health Sciences University of Rome ''Foro Italico”, Piazza Lauro de Bosis 6, 00135, Rome, ItalyLaboratory of Molecular Virology and Antimicrobial Immunity, Department of Science, Roma Tre University, 00146, Rome, Italy; Neuroimmunology Unit, IRCCS Fondazione Santa Lucia, Via del fosso di fiorano 64, 00143, Rome, ItalyLaboratory of Resolution of Neuroinflammation, IRCCS Fondazione Santa Lucia, Via del fosso di fiorano 64, 00143, Rome, Italy; PhD program in Immunology, Molecular Medicine and Applied biotechnologies, University of Rome “Tor Vergata”, 00133, Rome, ItalyLaboratory of Neurochemistry, IRCCS Fondazione Santa Lucia, Via del fosso di fiorano 64, 00143, Rome, Italy; Department of Systems Medicine, University of Roma ''Tor Vergata'', 00133, Rome, ItalyLaboratory of Neurochemistry, IRCCS Fondazione Santa Lucia, Via del fosso di fiorano 64, 00143, Rome, Italy; Department of Experimental Medicine, University of Roma ''La Sapienza'', 00161, Rome, ItalyNeuroimmunology Unit, IRCCS Fondazione Santa Lucia, Via del fosso di fiorano 64, 00143, Rome, ItalyDepartment of Biology, University of Rome “Tor Vergata”, via della ricerca scientifica, 00133, Rome, ItalyInstitute of Translational Pharmacology, National Research Council, Via del fosso del cavaliere 100, 00133, Rome, Italy; Laboratory of Resolution of Neuroinflammation, IRCCS Fondazione Santa Lucia, Via del fosso di fiorano 64, 00143, Rome, ItalyDepartment of Biology, University of Rome “Tor Vergata”, via della ricerca scientifica, 00133, Rome, ItalyUnit of Neurology, Fondazione PTV Policlinico Tor Vergata, Viale Oxford 81, 00133, Rome, Italy; Department of Systems Medicine, University of Roma ''Tor Vergata'', 00133, Rome, Italy; Laboratory of Experimental Neurology, IRCCS Fondazione Santa Lucia, Via del fosso di fiorano 64, 00143, Rome, ItalyLaboratory of Neurochemistry, IRCCS Fondazione Santa Lucia, Via del fosso di fiorano 64, 00143, Rome, Italy; Institute of Translational Pharmacology, National Research Council, Via del fosso del cavaliere 100, 00133, Rome, ItalyLaboratory of Neurochemistry, IRCCS Fondazione Santa Lucia, Via del fosso di fiorano 64, 00143, Rome, Italy; Institute of Translational Pharmacology, National Research Council, Via del fosso del cavaliere 100, 00133, Rome, ItalyAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the selective loss of motor neurons. The contribution of peripheral organs remains incompletely understood. We focused our attention on brown adipose tissue (BAT) and its secreted extracellular vesicles (EVs) given their role in regulating systemic energy balance. In this study, we employed a multi-omics approach, including RNA sequencing (GEO identifier GSE273052) and proteomics (ProteomeXchange identifier PXD054147), to investigate the alterations in BAT and its EVs in the SOD1-G93A mouse model of ALS. Our results revealed consistent changes in the proteomic and transcriptomic profiles of BAT from SOD1-G93A mice, highlighting alterations such as mitochondrial dysfunction and impaired differentiation capacity. Specifically, primary brown adipocytes (PBAs) from SOD1-G93A mice exhibited differentiation impairment, respiratory defects, and alterations in mitochondrial dynamics. Furthermore, the BAT-derived EVs from SOD1-G93A mice displayed distinct changes in size distribution and cargo content. In parallel, such EVs negatively impacted the differentiation and homeostasis of C2C12 murine myoblasts, as well as induced atrophy in C2C12-derived myotubes. These findings suggest that BAT undergoes pathological perturbations in ALS mouse model and could impact on skeletal muscle homeostasis through the secretion of dysfunctional EVs.http://www.sciencedirect.com/science/article/pii/S2405844025001811 |
| spellingShingle | Marco Rosina Silvia Scaricamazza Flaminia Riggio Gianmarco Fenili Flavia Giannessi Alessandro Matteocci Valentina Nesci Illari Salvatori Daniela F. Angelini Katia Aquilano Valerio Chiurchiù Daniele Lettieri Barbato Nicola Biagio Mercuri Cristiana Valle Alberto Ferri Brown Adipose Tissue undergoes pathological perturbations and shapes C2C12 myoblast homeostasis in the SOD1-G93A mouse model of Amyotrophic Lateral Sclerosis Heliyon |
| title | Brown Adipose Tissue undergoes pathological perturbations and shapes C2C12 myoblast homeostasis in the SOD1-G93A mouse model of Amyotrophic Lateral Sclerosis |
| title_full | Brown Adipose Tissue undergoes pathological perturbations and shapes C2C12 myoblast homeostasis in the SOD1-G93A mouse model of Amyotrophic Lateral Sclerosis |
| title_fullStr | Brown Adipose Tissue undergoes pathological perturbations and shapes C2C12 myoblast homeostasis in the SOD1-G93A mouse model of Amyotrophic Lateral Sclerosis |
| title_full_unstemmed | Brown Adipose Tissue undergoes pathological perturbations and shapes C2C12 myoblast homeostasis in the SOD1-G93A mouse model of Amyotrophic Lateral Sclerosis |
| title_short | Brown Adipose Tissue undergoes pathological perturbations and shapes C2C12 myoblast homeostasis in the SOD1-G93A mouse model of Amyotrophic Lateral Sclerosis |
| title_sort | brown adipose tissue undergoes pathological perturbations and shapes c2c12 myoblast homeostasis in the sod1 g93a mouse model of amyotrophic lateral sclerosis |
| url | http://www.sciencedirect.com/science/article/pii/S2405844025001811 |
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