Cholic acid and deoxycholic acid induce skeletal muscle atrophy through a mechanism dependent on TGR5 receptor
Author
dc.contributor.author
Abrigo, Johanna
Author
dc.contributor.author
González, Francisco
Author
dc.contributor.author
Aguirre, Francisco
Author
dc.contributor.author
Tacchi, Franco
Author
dc.contributor.author
González, Andrea
Author
dc.contributor.author
Meza, María Paz
Author
dc.contributor.author
Simón, Felipe
Author
dc.contributor.author
Cabrera, Daniel
Author
dc.contributor.author
Arrese, Marco
Author
dc.contributor.author
Karpen, Saúl
Author
dc.contributor.author
Cabello Verrugio, Claudio
Admission date
dc.date.accessioned
2020-06-23T20:52:18Z
Available date
dc.date.available
2020-06-23T20:52:18Z
Publication date
dc.date.issued
2020
Cita de ítem
dc.identifier.citation
J Cell Physiol. 2020;1–13
es_ES
Identifier
dc.identifier.other
10.1002/jcp.29839
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/175648
Abstract
dc.description.abstract
Skeletal muscle atrophy is characterized by the degradation of myofibrillar proteins, such as myosin heavy chain or troponin. An increase in the expression of two muscle-specific E3 ligases, atrogin-1 and MuRF-1, and oxidative stress are involved in muscle atrophy. Patients with chronic liver diseases (CLD) develop muscle wasting. Several bile acids increase in plasma during cholestatic CLD, among them, cholic acid (CA) and deoxycholic acid (DCA). The receptor for bile acids, TGR5, is expressed in healthy skeletal muscles. TGR5 is involved in the regulation of muscle differentiation and metabolic changes. In this paper, we evaluated the participation of DCA and CA in the generation of an atrophic condition in myotubes and isolated fibers from the muscle extracted from wild-type (WT) and TGR5-deficient (TGR5(-/-)) male mice. The results show that DCA and CA induce a decrease in diameter, and myosin heavy chain (MHC) protein levels, two typical atrophic features in C2C12 myotubes. We also observed similar results when INT-777 agonists activated the TGR5 receptor. To evaluate the participation of TGR5 in muscle atrophy induced by DCA and CA, we used a culture of muscle fiber isolated from WT and TGR5(-/-) mice. Our results show that DCA and CA decrease the fiber diameter and MHC protein levels, and there is an increase in atrogin-1, MuRF-1, and oxidative stress in WT fibers. The absence of TGR5 in fibers abolished all these effects induced by DCA and CA. Thus, we demonstrated that CS and deoxycholic acid induce skeletal muscle atrophy through TGR5 receptor.
es_ES
Patrocinador
dc.description.sponsorship
BASAL Grant CEDENNA
AFB180001
Programa de Cooperacion Cientifica ECOS-CONICYT
C16S02
Millennium Institute on Immunology and Immunotherapy
P09-016-F
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
21161353
Nucleus of Ion ChannelsAssociated Diseases
MiNICAD
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
AFB170005
National Fund for Science and Technological Development
Fondecyt 11171001
Fondecyt 1161288
Fondecyt 1161646