Enoxacin induces oxidative metabolism and mitigates obesity by regulating adipose tissue miRNA expression.

Autor:	Rocha AL; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; Program in Genetics and Molecular Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; Department of Biophysics, São Paulo School of Medicine, Federal University of São Paulo, São Paulo, Brazil.; Program in Biotechnology, Federal University of São Paulo, São Paulo, Brazil., de Lima TI; Obesity and Comorbidities Research Center (OCRC), University of Campinas, Campinas, Brazil.; Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; Laboratory of Integrative Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., de Souza GP; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; Program in Genetics and Molecular Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; Obesity and Comorbidities Research Center (OCRC), University of Campinas, Campinas, Brazil., Corrêa RO; Program in Genetics and Molecular Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil., Ferrucci DL; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; National Institute of Science and Technology in Photonics Applied to Cell Biology (INFABiC), University of Campinas, Campinas, Brazil., Rodrigues B; Department of Adapted Physical Activity, School of Physical Education, University of Campinas, Campinas, Brazil., Lopes-Ramos C; Center of Molecular Oncology, Sírio-Libanês Hospital, São Paulo, Brazil.; Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, USA., Nilsson D; Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Sweden.; The Lundberg Laboratory for Diabetes Research, University of Gothenburg, Sweden., Knittel TL; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; Program in Genetics and Molecular Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; Obesity and Comorbidities Research Center (OCRC), University of Campinas, Campinas, Brazil., Castro PR; Program in Genetics and Molecular Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil., Fernandes MF; Program in Genetics and Molecular Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil., Dos Santos Martins F; Laboratory of Biotherapeutics Agents, Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil., Parmigiani RB; Center of Molecular Oncology, Sírio-Libanês Hospital, São Paulo, Brazil., Silveira LR; Obesity and Comorbidities Research Center (OCRC), University of Campinas, Campinas, Brazil.; Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil., Carvalho HF; Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; National Institute of Science and Technology in Photonics Applied to Cell Biology (INFABiC), University of Campinas, Campinas, Brazil., Auwerx J; Laboratory of Integrative Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Vinolo MAR; Program in Genetics and Molecular Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; Obesity and Comorbidities Research Center (OCRC), University of Campinas, Campinas, Brazil.; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.; Experimental Medicine Research Cluster (EMRC), Campinas, Brazil., Boucher J; Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Sweden.; The Lundberg Laboratory for Diabetes Research, University of Gothenburg, Sweden.; Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Mori MA; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil. morima@unicamp.br.; Program in Genetics and Molecular Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; Department of Biophysics, São Paulo School of Medicine, Federal University of São Paulo, São Paulo, Brazil.; Program in Biotechnology, Federal University of São Paulo, São Paulo, Brazil.; Obesity and Comorbidities Research Center (OCRC), University of Campinas, Campinas, Brazil.; Experimental Medicine Research Cluster (EMRC), Campinas, Brazil.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2020 Dec 02; Vol. 6 (49). Date of Electronic Publication: 2020 Dec 02 (Print Publication: 2020).
DOI:	10.1126/sciadv.abc6250
Abstrakt:	MicroRNAs (miRNAs) have been implicated in oxidative metabolism and brown/beige adipocyte identity. Here, we tested whether widespread changes in miRNA expression promoted by treatment with the small-molecule enoxacin cause browning and prevent obesity. Enoxacin mitigated diet-induced obesity in mice, and this was associated with increased energy expenditure. Consistently, subcutaneous white and brown adipose tissues and skeletal muscle of enoxacin-treated mice had higher levels of markers associated with thermogenesis and oxidative metabolism. These effects were cell autonomous since they were recapitulated in vitro in murine and human cell models. In preadipocytes, enoxacin led to a reduction of miR-34a-5p expression and up-regulation of its target genes (e.g., Fgfr1 , Klb , and Sirt1 ), thus increasing FGF21 signaling and promoting beige adipogenesis. Our data demonstrate that enoxacin counteracts obesity by promoting thermogenic signaling and inducing oxidative metabolism in adipose tissue and skeletal muscle in a mechanism that involves, at least in part, miRNA-mediated regulation. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
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