Year: 2022
Type: article
Abstract: Cholestatic chronic liver disease is characterized by developing sarcopenia and elevated serum levels of bile acids. Sarcopenia is a skeletal muscle disorder with the hallmarks of muscle weakness, muscle mass loss, and muscle strength decline. Our previous report demonstrated that deoxycholic acid (DCA) and cholic acid (CA), through the membrane receptor TGR5, induce a sarcopenia-like phenotype in myotubes and muscle fibers. The present study aimed to evaluate the impact of DCA and CA on mitochondrial mass and function in muscle fibers and the role of the TGR5 receptor. To this end, muscle fibers obtained from wild-type and TGR5−/− mice were incubated with DCA and CA. Our results indicated that DCA and CA decreased mitochondrial mass, DNA, and potential in a TGR5-dependent fashion. Furthermore, with TGR5 participation, DCA and CA also reduced the oxygen consumption rate and complexes I and II from the mitochondrial electron transport chain. In addition, DCA and CA generated more mitochondrial reactive oxygen species than the control, which were abolished in TGR5−/− mice muscle fibers. Our results indicate that DCA and CA induce mitochondrial dysfunction in muscle fibers through a TGR5-dependent mechanism.
Source: Antioxidants
Institutions: Universidad de Santiago de Chile, Universidad Andrés Bello, Millennium Institute on Immunology and Immunotherapy, Center for the Development of Nanoscience and Nanotechnology, Pontificia Universidad Católica de Chile, Universidad Bernardo O'Higgins, Millennium Nucleus of Ion Channel Associated Diseases, University of Chile
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,303
Funders: European Commission, Universidad Andrés Bello, Instituto Milenio en Inmunología e Inmunoterapia, Agencia Nacional de Investigación y Desarrollo, Centro de Envejecimiento y Regeneración, Pontificia Universidad Católica de Chile, Fondo Nacional de Desarrollo Científico y Tecnológico, Centro para el Desarrollo de la Nanociencia y la Nanotecnología
Awards: G1189038995, G1276511734, G1569017989, G1846262052, DECIPHERING MUSCLE-LIVER CONNECTIONS IN MAFLD EXPERIMENTAL AND CLINICAL STUDIES, G2746400043, TARGETING ANEMIA THROUGH ENHANCING MITOCHONDRIAL DYNAMICS AND MITOPHAGY INVESTIGATION OF TWO NOVEL MITOCONDRIAL PROTEINS, G3027315668, G3054552592, G3272417151, SIN INFORMACION, G3325840243, G3375394455, G3832433737, G3965763869, G410823344, RANTES A NEW MYOKINE THAT PARTICIPATES IN SARCOPENIA INDUCED BY BILE ACIDS DURING CHRONIC LIVER DISEASES, G4314926160, G4346909545, G449605353, G4606729794, G4708858826, G5135215175, G5180710010, European-Latin American network for the assessment of biomarkers to predict and diagnose hepatobiliary malignancies and characterization of risk factors for cancer development, G5634318962, ASSESSING THE ROLE OF BILE ACIDS (BA) IN NASH-RELATED HEPATOCELLULAR CARCINOMA, G5896778222, G5987201865, CENTER FOR AGING AND REGENERATION, G6012192292, G6481653303, G6593763517, G6831707379, G7488491121, MILLENNIUM INSTITUTE ON IMMUNOLOGY AND IMMUNOTHERAPY, G7803641602, G8365428686, G907784011, G92388697, PARTICIPATION OF ENDOTHELIAL TRPC6 AND TRPM7 ION CHANNELS IN COAGULATION INDUCED BY ADRENERGIC STIMULATION.
OpenAlex ID: W4293686355