Sarcopenia induced by chronic liver disease in mice requires the expression of the bile acids membrane receptor TGR5
Author
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Abrigo, Johanna
Author
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Campos, Fabián
Author
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González, Francisco
Author
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Aguirre, Francisco
Author
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González, Andrea
Author
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Huerta Salgado, Camila
Author
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Conejeros, Sabrina
Author
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Simon, Felipe
Author
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Arrese, Marco
Author
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Cabrera, Daniel
Author
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Elorza, Alvaro A.
Author
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Cabello Verrugio, Claudio
Admission date
dc.date.accessioned
2021-05-04T21:52:27Z
Available date
dc.date.available
2021-05-04T21:52:27Z
Publication date
dc.date.issued
2020
Cita de ítem
dc.identifier.citation
Int. J. Mol. Sci. 2020, 21, 7922
es_ES
Identifier
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10.3390/ijms21217922
Identifier
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https://repositorio.uchile.cl/handle/2250/179427
Abstract
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Sarcopenia is a condition of muscle dysfunction, commonly associated with chronic liver disease (CLD), characterized by a decline in muscle strength, the activation of the ubiquitin-proteasome system (UPS), and oxidative stress. We recently described a murine model of CLD-induced sarcopenia by intake of hepatotoxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), which presents an increase in plasma bile acids (BA). BA induced skeletal muscle atrophy through a mechanism dependent on the Takeda G protein-coupled receptor 5 (TGR5) receptor. In the present study, we evaluated the role of TGR5 signaling in the development of sarcopenia using a model of DDC-induced CLD in C57BL6 wild-type (WT) mice and mice deficient in TGR5 expression (TGR5(-/-) mice). The results indicate that the decline in muscle function and contractibility induced by the DDC diet is dependent on TGR5 expression. TGR5 dependence was also observed for the decrease in fiber diameter and sarcomeric proteins, as well as for the fast-to-slow shift in muscle fiber type. UPS overactivation, indicated by increased atrogin-1/MAFbx (atrogin-1) and muscle RING-finger protein-1 (MuRF-1) protein levels and oxidative stress, was abolished in tibialis anterior muscles from TGR5(-/-) mice. Our results collectively suggest that all sarcopenia features induced by the DDC-supplemented diet in mice are dependent on TGR5 receptor expression.
es_ES
Patrocinador
dc.description.sponsorship
National Fund for Science and Technological Development
FONDECYT 1200944
1161646
1201039
1161288
1180983
1191145
11171001
Millennium Institute on Immunology and Immunotherapy
P09-016-F
Programa de Cooperacion Cientifica ECOS-ANID
C16S02
National Research And Development Agency (ANID), Government of Chile
AFB180001
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
AFB170005
Iniciativa Cientifica Milenio (ANID, Chile)
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
CONICYT FONDECYT
1200944