Sarcopenia in a mice model of chronic liver disease: role of the ubiquitin–proteasome system and oxidative stress

Fabián Campos, Johanna Abrigo, Francisco Aguirre, Bruno Garcés, Marco Arrese, Saul Karpen, Daniel Cabrera, Marcelo E. Andía, Felipe Simon, Claudio Cabello-Verrugio*

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

33 Citas (Scopus)


Sarcopenia is the loss of muscle mass and strength produced by aging or secondary to chronic diseases such as chronic liver disease (CLD). Although not all types of sarcopenia involve the same features, the most common are decreased fiber diameter and myosin heavy chain (MHC) levels, increased activity of ubiquitin–proteasome system (UPS) and reactive oxygen species (ROS). In this study, we aim to characterize the development of sarcopenia secondary to CLD induced by the hepatotoxin 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). For this purpose, four-months-old male C57BL6 mice were fed with normal diet or DDC supplemented diet for 6 weeks. Functional tests to evaluate muscle strength, mobility, and motor skills were performed in alive mice. The muscle strength in isolated gastrocnemius was also assayed via electrophysiological measurements. Morphometric measures of fibers’ diameter, total and ubiquitinated protein levels of myosin heavy chain (MHC), E3 ubiquitin ligases, ROS, and oxidation-dependent modified proteins in gastrocnemius tissue were also determined. Our results demonstrated that mice fed the DDC diet developed muscle wasting as evidenced by a loss of muscle mass and decreased muscle strength. The muscles of mice fed with DDC diet have a decreased diameter of fibers and MHC levels, also as increased MuRF-1 and atrogin-1 protein levels, ROS levels, and oxidation-modified protein levels. Additionally, control and DDC mice have the same food and water intake as well as mobility. Our results demonstrate mice with CLD develop sarcopenia involving decreased levels of myofibrillar proteins, increased UPS, and oxidative stress, but not for impaired caloric intake or immobility.

Idioma originalInglés
Páginas (desde-hasta)1503-1519
Número de páginas17
PublicaciónPflugers Archiv European Journal of Physiology
EstadoPublicada - 1 oct. 2018
Publicado de forma externa

Nota bibliográfica

Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.


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