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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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Rocha, Andrea Livia [1, 2, 3, 4] ; de Lima, Tanes Imamura [5, 6, 7] ; de Souza, Gerson Profeta [1, 2, 6] ; Correa, Renan Oliveira [8, 2] ; Ferrucci, Danilo Lopes [5, 1, 9] ; Rodrigues, Bruno [10] ; Lopes-Ramos, Camila [11, 12] ; Nilsson, Daniel [13, 14] ; Knittel, Thiago Leite [1, 2, 6] ; Castro, Pollyana Ribeiro [8, 2] ; Fernandes, Mariane Font [8, 2] ; Martins, Flaviano Dos Santos [15] ; Parmigiani, Raphael Bessa [11] ; Silveira, Leonardo Reis [5, 6] ; Carvalho, Hernandes F. [5, 9] ; Auwerx, Johan [7] ; Vinolo, Marco Aurelio R. [8, 2, 6, 16] ; Boucher, Jeremie [13, 14, 17] ; Mori, Marcelo A. [1, 2, 3, 4, 6, 16]
Total Authors: 19
Affiliation:
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[1] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Campinas - Brazil
[2] Univ Estadual Campinas, Inst Biol, Program Genet & Mol Biol, Campinas - Brazil
[3] Univ Fed Sao Paulo, Sao Paulo Sch Med, Dept Biophys, Sao Paulo - Brazil
[4] Univ Fed Sao Paulo, Program Biotechnol, Sao Paulo - Brazil
[5] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, Campinas - Brazil
[6] Univ Estadual Campinas, Obes & Comorbid Res Ctr OCRC, Campinas - Brazil
[7] Ecole Polytech Fed Lausanne, Lab Integrat Syst Physiol, Interfac Inst Bioengn, Lausanne - Switzerland
[8] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Campinas - Brazil
[9] Univ Estadual Campinas, Natl Inst Sci & Technol Photon Appl Cell Biol Inf, Campinas - Brazil
[10] Univ Estadual Campinas, Sch Phys Educ, Dept Adapted Phys Act, Campinas - Brazil
[11] Sirio Libanes Hosp, Ctr Mol Oncol, Sao Paulo - Brazil
[12] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA - USA
[13] Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg - Sweden
[14] Univ Gothenburg, Lundberg Lab Diabet Res, Gothenburg - Sweden
[15] Univ Fed Minas Gerais, Inst Biol Sci, Dept Microbiol, Lab Biotherapeut Agents, Belo Horizonte, MG - Brazil
[16] Expt Med Res Cluster EMRC, Campinas - Brazil
[17] AstraZeneca, Biosci Metab Res & Early Dev Cardiovasc Renal & M, BioPharmaceut R&D, Gothenburg - Sweden
Total Affiliations: 17
Document type: Journal article
Source: SCIENCE ADVANCES; v. 6, n. 49 DEC 2020.
Web of Science Citations: 0
Abstract

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 m urine 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. (AU)

FAPESP's process: 10/52557-0 - Identification of mechanisms responsible for beneficial effects of calorie restriction
Grantee:Marcelo Alves da Silva Mori
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 17/01184-9 - CAMeLEOm: cross-species analysis of metabolic, lifespan effects and omics of dietary restriction mimetics
Grantee:Marcelo Alves da Silva Mori
Support type: Research Projects - Thematic Grants
FAPESP's process: 18/15313-8 - Investigation of the molecular mechanisms involved in the interaction between microbiota-derived metabolites and host cells during inflammation
Grantee:Marco Aurélio Ramirez Vinolo
Support type: Research Grants - Young Investigators Grants - Phase 2
FAPESP's process: 16/23142-3 - Interaction between HIF-1 and short-chain fatty acids in the intestine: what is the role of HIF-1 acetylation?
Grantee:Renan Oliveira Corrêa
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 17/07975-8 - Exploring the role of adipose tissue-derived circulating miRNAs in the beneficial effects of exercise training
Grantee:Marcelo Alves da Silva Mori
Support type: Regular Research Grants
FAPESP's process: 16/24163-4 - Screening and characterization of fluoroquinolone compounds and their influence on the biogenesis of miRNAs
Grantee:Gerson Profeta de Souza
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 15/01316-7 - Dicer, miRNAs and the control of mitochondrial function in the context of aging and caloric restriction
Grantee:Marcelo Alves da Silva Mori
Support type: Regular Research Grants
FAPESP's process: 16/12294-7 - Dicer signalling in adipocytes controlling immune function and activation of beige cells in adipose tissue
Grantee:Andréa Livia Silva Rocha
Support type: Scholarships in Brazil - Doctorate