BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice
- Autores
- Pereyra, Andrea Soledad; Wang, Zhong-Min; Messi, Maria 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.
Fil: Pereyra, Andrea Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina. Wake Forest School of Medicine; Estados Unidos
Fil: Wang, Zhong-Min. Wake Forest School of Medicine; Estados Unidos
Fil: Messi, Maria Laura. Wake Forest School of Medicine; Estados Unidos
Fil: Zhang, Tan. Wake Forest School of Medicine; Estados Unidos
Fil: Wu, Hanzhi. Wake Forest School of Medicine; Estados Unidos
Fil: Register, Thomas C.. Wake Forest School of Medicine; Estados Unidos
Fil: Forbes, Elizabeth. Wake Forest School of Medicine; Estados Unidos
Fil: Devarie Baez, Nelmi O.. Wake Forest School of Medicine; Estados Unidos
Fil: Files, Daniel Clark. Wake Forest School of Medicine; Estados Unidos
Fil: Abba, Martín Carlos. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Furdui, Cristina. Wake Forest School of Medicine; Estados Unidos
Fil: Delbono, Osvaldo. Wake Forest School of Medicine; Estados Unidos - Materia
-
Aging
Body Fat
Calpain
Sarcopenia
Skeletal Muscle - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/48769
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, Maria LauraZhang, TanWu, HanzhiRegister, Thomas C.Forbes, ElizabethDevarie Baez, Nelmi O.Files, Daniel ClarkAbba, Martín CarlosFurdui, CristinaDelbono, OsvaldoAgingBody FatCalpainSarcopeniaSkeletal Musclehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Loss 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.Fil: Pereyra, Andrea Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina. Wake Forest School of Medicine; Estados UnidosFil: Wang, Zhong-Min. Wake Forest School of Medicine; Estados UnidosFil: Messi, Maria Laura. Wake Forest School of Medicine; Estados UnidosFil: Zhang, Tan. Wake Forest School of Medicine; Estados UnidosFil: Wu, Hanzhi. Wake Forest School of Medicine; Estados UnidosFil: Register, Thomas C.. Wake Forest School of Medicine; Estados UnidosFil: Forbes, Elizabeth. Wake Forest School of Medicine; Estados UnidosFil: Devarie Baez, Nelmi O.. Wake Forest School of Medicine; Estados UnidosFil: Files, Daniel Clark. Wake Forest School of Medicine; Estados UnidosFil: Abba, Martín Carlos. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Furdui, Cristina. Wake Forest School of Medicine; Estados UnidosFil: Delbono, Osvaldo. Wake Forest School of Medicine; Estados UnidosGerontological Soc Amer2017-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/48769Pereyra, Andrea Soledad; Wang, Zhong-Min; Messi, Maria Laura; Zhang, Tan; Wu, Hanzhi; et al.; BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice; Gerontological Soc Amer; Journals Of Gerontology Series A-biological Sciences And Medical Sciences; 72; 8; 8-2017; 1045-10531079-5006CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1093/gerona/glw192info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/biomedgerontology/article/72/8/1045/2328593info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:15Zoai:ri.conicet.gov.ar:11336/48769instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:57:16.186CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| 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 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, Maria 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, Maria 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, Maria 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 |
Aging Body Fat Calpain Sarcopenia Skeletal Muscle |
| topic |
Aging Body Fat Calpain Sarcopenia Skeletal Muscle |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| 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. Fil: Pereyra, Andrea Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina. Wake Forest School of Medicine; Estados Unidos Fil: Wang, Zhong-Min. Wake Forest School of Medicine; Estados Unidos Fil: Messi, Maria Laura. Wake Forest School of Medicine; Estados Unidos Fil: Zhang, Tan. Wake Forest School of Medicine; Estados Unidos Fil: Wu, Hanzhi. Wake Forest School of Medicine; Estados Unidos Fil: Register, Thomas C.. Wake Forest School of Medicine; Estados Unidos Fil: Forbes, Elizabeth. Wake Forest School of Medicine; Estados Unidos Fil: Devarie Baez, Nelmi O.. Wake Forest School of Medicine; Estados Unidos Fil: Files, Daniel Clark. Wake Forest School of Medicine; Estados Unidos Fil: Abba, Martín Carlos. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina Fil: Furdui, Cristina. Wake Forest School of Medicine; Estados Unidos Fil: Delbono, Osvaldo. Wake Forest School of Medicine; Estados Unidos |
| 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. |
| publishDate |
2017 |
| dc.date.none.fl_str_mv |
2017-08 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/48769 Pereyra, Andrea Soledad; Wang, Zhong-Min; Messi, Maria Laura; Zhang, Tan; Wu, Hanzhi; et al.; BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice; Gerontological Soc Amer; Journals Of Gerontology Series A-biological Sciences And Medical Sciences; 72; 8; 8-2017; 1045-1053 1079-5006 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/48769 |
| identifier_str_mv |
Pereyra, Andrea Soledad; Wang, Zhong-Min; Messi, Maria Laura; Zhang, Tan; Wu, Hanzhi; et al.; BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice; Gerontological Soc Amer; Journals Of Gerontology Series A-biological Sciences And Medical Sciences; 72; 8; 8-2017; 1045-1053 1079-5006 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
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eng |
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info:eu-repo/semantics/altIdentifier/doi/10.1093/gerona/glw192 info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/biomedgerontology/article/72/8/1045/2328593 |
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openAccess |
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Gerontological Soc Amer |
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Gerontological Soc Amer |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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