title: High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration: Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis.
abstract: Obesity can lead to skeletal muscle atrophy, a pathological condition characterized by the loss of strength and muscle mass. A feature of muscle atrophy is a decrease of myofibrillar proteins as a result of ubiquitin proteasome pathway overactivation, as evidenced by increased expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF-1. Additionally, other mechanisms are related to muscle wasting, including oxidative stress, myonuclear apoptosis, and autophagy. Stem cells are an emerging therapy in the treatment of chronic diseases such as high fat diet-induced obesity. Mesenchymal stem cells (MSCs) are a population of self-renewable and undifferentiated cells present in the bone marrow and other mesenchymal tissues of adult individuals. The present study is the first to analyze the effects of systemic MSC administration on high fat diet-induced skeletal muscle atrophy in the tibialis anterior of mice. Treatment with MSCs reduced losses of muscle strength and mass, decreases of fiber diameter and myosin heavy chain protein levels, and fiber type transitions. Underlying these antiatrophic effects, MSC administration also decreased ubiquitin proteasome pathway activation, oxidative stress, and myonuclear apoptosis. These results are the first to indicate that systemically administered MSCs could prevent muscle wasting associated with high fat diet-induced obesity and diabetes.
authors: Laboratorio de Biologia y Fisiopatologia Molecular, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas y Facultad de Medicina, Universidad Andres Bello, 8370146 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, 8370146 Santiago, Chile.
authors: Johanna
authors: 0000-0002-5598-513X
authors: J
authors: Abrigo
authors: Laboratorio de Biologia y Fisiopatologia Molecular, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas y Facultad de Medicina, Universidad Andres Bello, 8370146 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, 8370146 Santiago, Chile.
authors: Juan Carlos
authors: 0000-0002-0927-218X
authors: JC
authors: Rivera
authors: Laboratorio de Biologia y Fisiopatologia Molecular, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas y Facultad de Medicina, Universidad Andres Bello, 8370146 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, 8370146 Santiago, Chile.
authors: Javier
authors: J
authors: Aravena
authors: Departamento de Ciencias Quimicas y Biologicas, Facultad de Salud, Universidad Bernardo O Higgins, 8370993 Santiago, Chile; Departamento de Gastroenterologıa, Facultad de Medicina, Pontificia Universidad Católica de Chile, 8330024 Santiago, Chile.
authors: Daniel
authors: D
authors: Cabrera
authors: Millennium Institute on Immunology and Immunotherapy, 8370146 Santiago, Chile; Laboratorio de Fisiologia Integrativa, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas y Facultad de Medicina, Universidad Andres Bello, 8370146 Santiago, Chile.
authors: Felipe
authors: F
authors: Simon
authors: Centro de Medicina Regenerativa, Facultad de Medicina, Clinica Alemana, Universidad del Desarrollo, 7710162 Santiago, Chile.
authors: Fernando
authors: F
authors: Ezquer
authors: Centro de Medicina Regenerativa, Facultad de Medicina, Clinica Alemana, Universidad del Desarrollo, 7710162 Santiago, Chile.
authors: Marcelo
authors: 0000-0002-2064-3041
authors: M
authors: Ezquer
authors: Laboratorio de Biologia y Fisiopatologia Molecular, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas y Facultad de Medicina, Universidad Andres Bello, 8370146 Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, 8370146 Santiago, Chile.
authors: Claudio
authors: 0000-0001-7273-2102
authors: C
authors: Cabello-Verrugio
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D018995:Myosin Heavy Chains / Q000378:metabolism; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D017382:Reactive Oxygen Species; D046988:Proteasome Endopeptidase Complex; D018995:Myosin Heavy Chains