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Please use this identifier to cite or link to this item: http://hdl.handle.net/1843/64806
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dc.creatorAndré L. Queirozpt_BR
dc.creatorMichael F. Hirshmanpt_BR
dc.creatorLuciane C. Albericipt_BR
dc.creatorIsis do Carmo Kettelhutpt_BR
dc.creatorLaurie J. Goodyearpt_BR
dc.creatorLeonardo R. Silveirapt_BR
dc.creatorSarah J. Lessardpt_BR
dc.creatorAmanda T. Ouchidapt_BR
dc.creatorHygor N. Araujopt_BR
dc.creatorDawit Albieiro Pinheiro Gonçalvespt_BR
dc.creatorDimitrius Santiago P. Simões Fróes Guimarãespt_BR
dc.creatorBruno G. Teodoropt_BR
dc.creatorKawai Sopt_BR
dc.creatorEnilza M. Espreaficopt_BR
dc.date.accessioned2024-02-27T16:24:29Z-
dc.date.available2024-02-27T16:24:29Z-
dc.date.issued2021-
dc.citation.volume51pt_BR
dc.citation.spage101226pt_BR
dc.citation.epage14pt_BR
dc.identifier.doihttps://doi.org/10.1016/j.molmet.2021.101226pt_BR
dc.identifier.issn2212-8778pt_BR
dc.identifier.urihttp://hdl.handle.net/1843/64806-
dc.description.resumoObjective MicroRNAs (miRNA) are known to regulate the expression of genes involved in several physiological processes including metabolism, mitochondrial biogenesis, proliferation, differentiation, and cell death. Methods Using “in silico” analyses, we identified 219 unique miRNAs that potentially bind to the 3′UTR region of a critical mitochondrial regulator, the peroxisome proliferator-activated receptor gamma coactivator (PGC) 1 alpha (Pgc1α). Of the 219 candidate miRNAs, miR-696 had one of the highest interactions at the 3′UTR of Pgc1α, suggesting that miR-696 may be involved in the regulation of Pgc1α. Results Consistent with this hypothesis, we found that miR-696 was highly expressed in the skeletal muscle of STZ-induced diabetic mice and chronic high-fat-fed mice. C2C12 muscle cells exposed to palmitic acid also exhibited a higher expression of miR-696. This increased expression corresponded with a reduced expression of oxidative metabolism genes and reduced mitochondrial respiration. Importantly, reducing miR-696 reversed decreases in mitochondrial activity in response to palmitic acid. Using C2C12 cells treated with the AMP-activated protein kinase (AMPK) activator AICAR and skeletal muscle from AMPKα2 dominant-negative (DN) mice, we found that the signaling mechanism regulating miR-696 did not involve AMPK. In contrast, overexpression of SNF1-AMPK-related kinase (SNARK) in C2C12 cells increased miR-696 transcription while knockdown of SNARK significantly decreased miR-696. Moreover, muscle-specific transgenic mice overexpressing SNARK exhibited a lower expression of Pgc1α, elevated levels of miR-696, and reduced amounts of spontaneous activity. Conclusions Our findings demonstrate that metabolic stress increases miR-696 expression in skeletal muscle cells, which in turn inhibits Pgc1α, reducing mitochondrial function. SNARK plays a role in this process as a metabolic stress signaling molecule inducing the expression of miR-696.pt_BR
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.description.sponsorshipFAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.format.mimetypepdfpt_BR
dc.languageengpt_BR
dc.publisherUniversidade Federal de Minas Geraispt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.departmentEEF - DEPARTAMENTO DE EDUCAÇÃO FÍSICApt_BR
dc.publisher.departmentEEFFTO - ESCOLA DE EDUCAÇÃO FISICA, FISIOTERAPIA E TERAPIA OCUPACIONALpt_BR
dc.publisher.initialsUFMGpt_BR
dc.relation.ispartofMolecular Metabolismpt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectMiR-696pt_BR
dc.subjectMitochondrial functionpt_BR
dc.subjectSkeletal musclept_BR
dc.subjectSNARKpt_BR
dc.subjectPgc1apt_BR
dc.subject.otherFisiologiapt_BR
dc.subject.otherMorfologia vegetalpt_BR
dc.subject.otherMúsculospt_BR
dc.subject.otherMitocôndriaspt_BR
dc.titleThe MicroRNA miR-696 is regulated by SNARK and reduces mitochondrial activity in mouse skeletal muscle through Pgc1α inhibitionpt_BR
dc.typeArtigo de Periódicopt_BR
dc.url.externahttps://www.sciencedirect.com/science/article/pii/S2212877821000715?via%3Dihubpt_BR
dc.identifier.orcidhttps://orcid.org/0000-0003-2621-3330pt_BR
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