BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice

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 wa...

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Detalles Bibliográficos
Autores principales: 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
Formato: Articulo
Lenguaje:Inglés
Publicado: 2017
Materias:
Ciencias Médicas
Aging
Body fat
Calpain
Sarcopenia
Skeletal muscle
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/87609
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-87609
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Aging
Body fat
Calpain
Sarcopenia
Skeletal muscle
spellingShingle Ciencias Médicas
Aging
Body fat
Calpain
Sarcopenia
Skeletal muscle
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
BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice
topic_facet Ciencias Médicas
Aging
Body fat
Calpain
Sarcopenia
Skeletal muscle
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.
format Articulo
Articulo
author 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_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_sort Pereyra, Andrea Soledad
title BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice
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
publishDate 2017
url http://sedici.unlp.edu.ar/handle/10915/87609
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