BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice
- Autores
- Pereyra, Andrea Soledad; Wang, Zhong Min; Messi, María Laura; Zhang, Tan; Wu, Hanzhi; Register, Thomas C.; Forbes, Elizabeth; Devarie Baez, Nelmi O.; Files, Daniel Clark; Abba, Martín Carlos; Furdui, Cristina; Delbono, Osvaldo
- Año de publicación
- 2017
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Loss of muscle mass and force with age leads to fall risk, mobility impairment, and reduced quality of life. This article shows that BDA-410, a calpain inhibitor, induced loss of body weight and fat but not lean mass or skeletal muscle proteins in a cohort of sedentary 23-month-old mice. Food and water intake and locomotor activity were not modified, whereas BDA-410 treatment decreased intramyocellular lipid and perigonadal fat, increased serum nonesterified fatty acids, and upregulated the genes mediating lipolysis and oxidation, lean phenotype, muscle contraction, muscle transcription regulation, and oxidative stress response. This finding is consistent with our recent report that lipid accumulation in skeletal myofibers is significantly correlated with slower fiber-contraction kinetics and diminished power in obese older adult mice. A proteomic analysis and immunoblot showed downregulation of the phosphatase PPP1R12B, which increases phosphorylated myosin half-life and modulates the calcium sensitivity of the contractile apparatus. This study demonstrates that BDA-410 exerts a beneficial effect on skeletal muscle contractility through new, alternative mechanisms, including enhanced lipolysis, upregulation of "lean phenotype-related genes," downregulation of the PP1R12B phosphatase, and enhanced excitation- contraction coupling. This single compound holds promise for treating age-dependent decline in muscle composition and strength.
Facultad de Ciencias Médicas
Instituto de Investigaciones Bioquímicas de La Plata
Centro de Investigaciones Inmunológicas Básicas y Aplicadas - Materia
-
Ciencias Médicas
Aging
Body fat
Calpain
Sarcopenia
Skeletal muscle - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by-nc-sa/4.0/
- Repositorio
.jpg)
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/87609
Ver los metadatos del registro completo
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BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent MicePereyra, Andrea SoledadWang, Zhong MinMessi, María LauraZhang, TanWu, HanzhiRegister, Thomas C.Forbes, ElizabethDevarie Baez, Nelmi O.Files, Daniel ClarkAbba, Martín CarlosFurdui, CristinaDelbono, OsvaldoCiencias MédicasAgingBody fatCalpainSarcopeniaSkeletal muscleLoss of muscle mass and force with age leads to fall risk, mobility impairment, and reduced quality of life. This article shows that BDA-410, a calpain inhibitor, induced loss of body weight and fat but not lean mass or skeletal muscle proteins in a cohort of sedentary 23-month-old mice. Food and water intake and locomotor activity were not modified, whereas BDA-410 treatment decreased intramyocellular lipid and perigonadal fat, increased serum nonesterified fatty acids, and upregulated the genes mediating lipolysis and oxidation, lean phenotype, muscle contraction, muscle transcription regulation, and oxidative stress response. This finding is consistent with our recent report that lipid accumulation in skeletal myofibers is significantly correlated with slower fiber-contraction kinetics and diminished power in obese older adult mice. A proteomic analysis and immunoblot showed downregulation of the phosphatase PPP1R12B, which increases phosphorylated myosin half-life and modulates the calcium sensitivity of the contractile apparatus. This study demonstrates that BDA-410 exerts a beneficial effect on skeletal muscle contractility through new, alternative mechanisms, including enhanced lipolysis, upregulation of "lean phenotype-related genes," downregulation of the PP1R12B phosphatase, and enhanced excitation- contraction coupling. This single compound holds promise for treating age-dependent decline in muscle composition and strength.Facultad de Ciencias MédicasInstituto de Investigaciones Bioquímicas de La PlataCentro de Investigaciones Inmunológicas Básicas y Aplicadas2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf1045-1053http://sedici.unlp.edu.ar/handle/10915/87609enginfo:eu-repo/semantics/altIdentifier/issn/1079-5006info:eu-repo/semantics/altIdentifier/doi/10.1093/gerona/glw192info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-03T10:49:31Zoai:sedici.unlp.edu.ar:10915/87609Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-03 10:49:31.212SEDICI (UNLP) - Universidad Nacional de La Platafalse |
| dc.title.none.fl_str_mv |
BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice |
| title |
BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice |
| spellingShingle |
BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice Pereyra, Andrea Soledad Ciencias Médicas Aging Body fat Calpain Sarcopenia Skeletal muscle |
| title_short |
BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice |
| title_full |
BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice |
| title_fullStr |
BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice |
| title_full_unstemmed |
BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice |
| title_sort |
BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice |
| dc.creator.none.fl_str_mv |
Pereyra, Andrea Soledad Wang, Zhong Min Messi, María Laura Zhang, Tan Wu, Hanzhi Register, Thomas C. Forbes, Elizabeth Devarie Baez, Nelmi O. Files, Daniel Clark Abba, Martín Carlos Furdui, Cristina Delbono, Osvaldo |
| author |
Pereyra, Andrea Soledad |
| author_facet |
Pereyra, Andrea Soledad Wang, Zhong Min Messi, María Laura Zhang, Tan Wu, Hanzhi Register, Thomas C. Forbes, Elizabeth Devarie Baez, Nelmi O. Files, Daniel Clark Abba, Martín Carlos Furdui, Cristina Delbono, Osvaldo |
| author_role |
author |
| author2 |
Wang, Zhong Min Messi, María Laura Zhang, Tan Wu, Hanzhi Register, Thomas C. Forbes, Elizabeth Devarie Baez, Nelmi O. Files, Daniel Clark Abba, Martín Carlos Furdui, Cristina Delbono, Osvaldo |
| author2_role |
author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Ciencias Médicas Aging Body fat Calpain Sarcopenia Skeletal muscle |
| topic |
Ciencias Médicas Aging Body fat Calpain Sarcopenia Skeletal muscle |
| dc.description.none.fl_txt_mv |
Loss of muscle mass and force with age leads to fall risk, mobility impairment, and reduced quality of life. This article shows that BDA-410, a calpain inhibitor, induced loss of body weight and fat but not lean mass or skeletal muscle proteins in a cohort of sedentary 23-month-old mice. Food and water intake and locomotor activity were not modified, whereas BDA-410 treatment decreased intramyocellular lipid and perigonadal fat, increased serum nonesterified fatty acids, and upregulated the genes mediating lipolysis and oxidation, lean phenotype, muscle contraction, muscle transcription regulation, and oxidative stress response. This finding is consistent with our recent report that lipid accumulation in skeletal myofibers is significantly correlated with slower fiber-contraction kinetics and diminished power in obese older adult mice. A proteomic analysis and immunoblot showed downregulation of the phosphatase PPP1R12B, which increases phosphorylated myosin half-life and modulates the calcium sensitivity of the contractile apparatus. This study demonstrates that BDA-410 exerts a beneficial effect on skeletal muscle contractility through new, alternative mechanisms, including enhanced lipolysis, upregulation of "lean phenotype-related genes," downregulation of the PP1R12B phosphatase, and enhanced excitation- contraction coupling. This single compound holds promise for treating age-dependent decline in muscle composition and strength. Facultad de Ciencias Médicas Instituto de Investigaciones Bioquímicas de La Plata Centro de Investigaciones Inmunológicas Básicas y Aplicadas |
| description |
Loss of muscle mass and force with age leads to fall risk, mobility impairment, and reduced quality of life. This article shows that BDA-410, a calpain inhibitor, induced loss of body weight and fat but not lean mass or skeletal muscle proteins in a cohort of sedentary 23-month-old mice. Food and water intake and locomotor activity were not modified, whereas BDA-410 treatment decreased intramyocellular lipid and perigonadal fat, increased serum nonesterified fatty acids, and upregulated the genes mediating lipolysis and oxidation, lean phenotype, muscle contraction, muscle transcription regulation, and oxidative stress response. This finding is consistent with our recent report that lipid accumulation in skeletal myofibers is significantly correlated with slower fiber-contraction kinetics and diminished power in obese older adult mice. A proteomic analysis and immunoblot showed downregulation of the phosphatase PPP1R12B, which increases phosphorylated myosin half-life and modulates the calcium sensitivity of the contractile apparatus. This study demonstrates that BDA-410 exerts a beneficial effect on skeletal muscle contractility through new, alternative mechanisms, including enhanced lipolysis, upregulation of "lean phenotype-related genes," downregulation of the PP1R12B phosphatase, and enhanced excitation- contraction coupling. This single compound holds promise for treating age-dependent decline in muscle composition and strength. |
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2017 |
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2017 |
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eng |
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