Urocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathways
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da UFMG |
| Texto Completo: | https://doi.org/10.1016/j.molmet.2022.101492 http://hdl.handle.net/1843/64803 https://orcid.org/0000-0003-2621-3330 |
Resumo: | CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico |
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2024-02-27T16:22:11Z2024-02-27T16:22:11Z20226010149216https://doi.org/10.1016/j.molmet.2022.1014922212-8778http://hdl.handle.net/1843/64803https://orcid.org/0000-0003-2621-3330CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFAPESP - Fundação de Amparo à Pesquisa do Estado de São PauloObjective Although it is well established that urocortin 2 (Ucn2), a peptide member of the corticotrophin releasing factor (CRF) family, and its specific corticotrophin-releasing factor 2 receptor (CRF2R) are highly expressed in skeletal muscle, the role of this peptide in the regulation of skeletal muscle mass and protein metabolism remains elusive. Methods To elucidate the mechanisms how Ucn2 directly controls protein metabolism in skeletal muscles of normal mice, we carried out genetic tools, physiological and molecular analyses of muscles in vivo and in vitro. Results Here, we demonstrated that Ucn2 overexpression activated cAMP signaling and promoted an expressive muscle hypertrophy associated with higher rates of protein synthesis and activation of Akt/mTOR and ERK1/2 signaling pathways. Furthermore, Ucn2 induced a decrease in mRNA levels of atrogin-1 and in autophagic flux inferred by an increase in the protein content of LC3-I, LC3-II and p62. Accordingly, Ucn2 reduced both the transcriptional activity of FoxO in vivo and the overall protein degradation in vitro through an inhibition of lysosomal proteolytic activity. In addition, we demonstrated that Ucn2 induced a fast-to-slow fiber type shift and improved fatigue muscle resistance, an effect that was completely blocked in muscles co-transfected with mitogen-activated protein kinase phosphatase 1 (MKP-1), but not with dominant-negative Akt mutant (Aktmt). Conclusions These data suggest that Ucn2 triggers an anabolic and anti-catabolic response in skeletal muscle of normal mice probably through the activation of cAMP cascade and participation of Akt and ERK1/2 signaling. These findings open new perspectives in the development of therapeutic strategies to cope with the loss of muscle mass.engUniversidade Federal de Minas GeraisUFMGBrasilEEF - DEPARTAMENTO DE EDUCAÇÃO FÍSICAEEFFTO - ESCOLA DE EDUCAÇÃO FISICA, FISIOTERAPIA E TERAPIA OCUPACIONALMolecular MetabolismHipertrofiaFadigaProteínasUrocortin 2HypertrophyFatigue resistancecAMPUrocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathwaysinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.sciencedirect.com/science/article/pii/S2212877822000618?via%3DihubNatalia LautherbachIsis C. KettelhutDawit Albieiro Pinheiro GonçalvesWilian A. SilveiraSílvia Paula-GomesRafael Rossi ValentimNeuza M. ZanonMarcelo G. PereiraElen H. MiyabaraLuiz C. C. Navegantesapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/64803/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALUrocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin_IGF-1 signaling pathways.pdfUrocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin_IGF-1 signaling pathways.pdfapplication/pdf2370064https://repositorio.ufmg.br/bitstream/1843/64803/2/Urocortin%202%20promotes%20hypertrophy%20and%20enhances%20skeletal%20muscle%20function%20through%20cAMP%20and%20insulin_IGF-1%20signaling%20pathways.pdf1c3411c7a29bde5823417ec8edad92d8MD521843/648032024-02-27 13:22:11.951oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2024-02-27T16:22:11Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
| dc.title.pt_BR.fl_str_mv |
Urocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathways |
| title |
Urocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathways |
| spellingShingle |
Urocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathways Natalia Lautherbach Urocortin 2 Hypertrophy Fatigue resistance cAMP Hipertrofia Fadiga Proteínas |
| title_short |
Urocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathways |
| title_full |
Urocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathways |
| title_fullStr |
Urocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathways |
| title_full_unstemmed |
Urocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathways |
| title_sort |
Urocortin 2 promotes hypertrophy and enhances skeletal muscle function through cAMP and insulin/IGF-1 signaling pathways |
| author |
Natalia Lautherbach |
| author_facet |
Natalia Lautherbach Isis C. Kettelhut Dawit Albieiro Pinheiro Gonçalves Wilian A. Silveira Sílvia Paula-Gomes Rafael Rossi Valentim Neuza M. Zanon Marcelo G. Pereira Elen H. Miyabara Luiz C. C. Navegantes |
| author_role |
author |
| author2 |
Isis C. Kettelhut Dawit Albieiro Pinheiro Gonçalves Wilian A. Silveira Sílvia Paula-Gomes Rafael Rossi Valentim Neuza M. Zanon Marcelo G. Pereira Elen H. Miyabara Luiz C. C. Navegantes |
| author2_role |
author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Natalia Lautherbach Isis C. Kettelhut Dawit Albieiro Pinheiro Gonçalves Wilian A. Silveira Sílvia Paula-Gomes Rafael Rossi Valentim Neuza M. Zanon Marcelo G. Pereira Elen H. Miyabara Luiz C. C. Navegantes |
| dc.subject.por.fl_str_mv |
Urocortin 2 Hypertrophy Fatigue resistance cAMP |
| topic |
Urocortin 2 Hypertrophy Fatigue resistance cAMP Hipertrofia Fadiga Proteínas |
| dc.subject.other.pt_BR.fl_str_mv |
Hipertrofia Fadiga Proteínas |
| description |
CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico |
| publishDate |
2022 |
| dc.date.issued.fl_str_mv |
2022 |
| dc.date.accessioned.fl_str_mv |
2024-02-27T16:22:11Z |
| dc.date.available.fl_str_mv |
2024-02-27T16:22:11Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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http://hdl.handle.net/1843/64803 |
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https://doi.org/10.1016/j.molmet.2022.101492 |
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2212-8778 |
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https://orcid.org/0000-0003-2621-3330 |
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https://doi.org/10.1016/j.molmet.2022.101492 http://hdl.handle.net/1843/64803 https://orcid.org/0000-0003-2621-3330 |
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2212-8778 |
| dc.language.iso.fl_str_mv |
eng |
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eng |
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Molecular Metabolism |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Universidade Federal de Minas Gerais |
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UFMG |
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Brasil |
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EEF - DEPARTAMENTO DE EDUCAÇÃO FÍSICA EEFFTO - ESCOLA DE EDUCAÇÃO FISICA, FISIOTERAPIA E TERAPIA OCUPACIONAL |
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Universidade Federal de Minas Gerais |
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reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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