Sarcopenia Induced by Chronic Liver Disease in Mice Requires the Expression of the Bile Acids Membrane Receptor TGR5
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 intak...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/21/7922 |
| _version_ | 1797549925519589376 |
|---|---|
| author | Johanna Abrigo Fabián Campos Francisco Gonzalez Francisco Aguirre Andrea Gonzalez Camila Huerta-Salgado Sabrina Conejeros Felipe Simon Marco Arrese Daniel Cabrera Alvaro A. Elorza Claudio Cabello-Verrugio |
| author_facet | Johanna Abrigo Fabián Campos Francisco Gonzalez Francisco Aguirre Andrea Gonzalez Camila Huerta-Salgado Sabrina Conejeros Felipe Simon Marco Arrese Daniel Cabrera Alvaro A. Elorza Claudio Cabello-Verrugio |
| author_sort | Johanna Abrigo |
| collection | DOAJ |
| description | 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 <i>wild-type</i> (WT) mice and mice deficient in TGR5 expression (TGR5<sup>−/−</sup> 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<sup>−/−</sup> mice. Our results collectively suggest that all sarcopenia features induced by the DDC-supplemented diet in mice are dependent on TGR5 receptor expression. |
| first_indexed | 2024-03-10T15:21:17Z |
| format | Article |
| id | doaj.art-fed8dc8ecbe843398cb3887375c0a3de |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:21:17Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fed8dc8ecbe843398cb3887375c0a3de2023-11-20T18:29:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012121792210.3390/ijms21217922Sarcopenia Induced by Chronic Liver Disease in Mice Requires the Expression of the Bile Acids Membrane Receptor TGR5Johanna Abrigo0Fabián Campos1Francisco Gonzalez2Francisco Aguirre3Andrea Gonzalez4Camila Huerta-Salgado5Sabrina Conejeros6Felipe Simon7Marco Arrese8Daniel Cabrera9Alvaro A. Elorza10Claudio Cabello-Verrugio11Laboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileLaboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileLaboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileLaboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileLaboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileLaboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileLaboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileMillennium Institute on Immunology and Immunotherapy, Santiago 8370146, ChileCentro de Envejecimiento y Regeneración (CARE), Departamento de Gastroenterología, Escuela de Medicina, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330077, ChileCentro de Envejecimiento y Regeneración (CARE), Departamento de Gastroenterología, Escuela de Medicina, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330077, ChileMillennium Institute on Immunology and Immunotherapy, Santiago 8370146, ChileLaboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, ChileSarcopenia 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 <i>wild-type</i> (WT) mice and mice deficient in TGR5 expression (TGR5<sup>−/−</sup> 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<sup>−/−</sup> mice. Our results collectively suggest that all sarcopenia features induced by the DDC-supplemented diet in mice are dependent on TGR5 receptor expression.https://www.mdpi.com/1422-0067/21/21/7922bile acidsmuscle atrophyTGR5 receptoroxidative stress |
| spellingShingle | Johanna Abrigo Fabián Campos Francisco Gonzalez Francisco Aguirre Andrea Gonzalez Camila Huerta-Salgado Sabrina Conejeros Felipe Simon Marco Arrese Daniel Cabrera Alvaro A. Elorza Claudio Cabello-Verrugio Sarcopenia Induced by Chronic Liver Disease in Mice Requires the Expression of the Bile Acids Membrane Receptor TGR5 International Journal of Molecular Sciences bile acids muscle atrophy TGR5 receptor oxidative stress |
| title | Sarcopenia Induced by Chronic Liver Disease in Mice Requires the Expression of the Bile Acids Membrane Receptor TGR5 |
| title_full | Sarcopenia Induced by Chronic Liver Disease in Mice Requires the Expression of the Bile Acids Membrane Receptor TGR5 |
| title_fullStr | Sarcopenia Induced by Chronic Liver Disease in Mice Requires the Expression of the Bile Acids Membrane Receptor TGR5 |
| title_full_unstemmed | Sarcopenia Induced by Chronic Liver Disease in Mice Requires the Expression of the Bile Acids Membrane Receptor TGR5 |
| title_short | Sarcopenia Induced by Chronic Liver Disease in Mice Requires the Expression of the Bile Acids Membrane Receptor TGR5 |
| title_sort | sarcopenia induced by chronic liver disease in mice requires the expression of the bile acids membrane receptor tgr5 |
| topic | bile acids muscle atrophy TGR5 receptor oxidative stress |
| url | https://www.mdpi.com/1422-0067/21/21/7922 |
| work_keys_str_mv | AT johannaabrigo sarcopeniainducedbychronicliverdiseaseinmicerequirestheexpressionofthebileacidsmembranereceptortgr5 AT fabiancampos sarcopeniainducedbychronicliverdiseaseinmicerequirestheexpressionofthebileacidsmembranereceptortgr5 AT franciscogonzalez sarcopeniainducedbychronicliverdiseaseinmicerequirestheexpressionofthebileacidsmembranereceptortgr5 AT franciscoaguirre sarcopeniainducedbychronicliverdiseaseinmicerequirestheexpressionofthebileacidsmembranereceptortgr5 AT andreagonzalez sarcopeniainducedbychronicliverdiseaseinmicerequirestheexpressionofthebileacidsmembranereceptortgr5 AT camilahuertasalgado sarcopeniainducedbychronicliverdiseaseinmicerequirestheexpressionofthebileacidsmembranereceptortgr5 AT sabrinaconejeros sarcopeniainducedbychronicliverdiseaseinmicerequirestheexpressionofthebileacidsmembranereceptortgr5 AT felipesimon sarcopeniainducedbychronicliverdiseaseinmicerequirestheexpressionofthebileacidsmembranereceptortgr5 AT marcoarrese sarcopeniainducedbychronicliverdiseaseinmicerequirestheexpressionofthebileacidsmembranereceptortgr5 AT danielcabrera sarcopeniainducedbychronicliverdiseaseinmicerequirestheexpressionofthebileacidsmembranereceptortgr5 AT alvaroaelorza sarcopeniainducedbychronicliverdiseaseinmicerequirestheexpressionofthebileacidsmembranereceptortgr5 AT claudiocabelloverrugio sarcopeniainducedbychronicliverdiseaseinmicerequirestheexpressionofthebileacidsmembranereceptortgr5 |