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Rocha 2020 Sci Adv

From Bioblast
Publications in the MiPMap
Rocha AL, de Lima TI, de Souza GP, Corrêa RO, Ferrucci DL, Rodrigues B, Lopes-Ramos C, Nilsson D, Knittel TL, Castro PR, Fernandes MF, Dos Santos Martins F, Parmigiani RB, Silveira LR, Carvalho HF, Auwerx J, Vinolo MAR, Boucher J, Mori MA (2020) Enoxacin induces oxidative metabolism and mitigates obesity by regulating adipose tissue miRNA expression. Sci Adv 6:eabc6250.

» PMID: 33268375 Open Access

Rocha Andrea Livia, de Lima Tanes Imamura, de Souza Gerson Profeta, Oliveira Correa Renan, Lopes Ferrucci Danilo, Rodrigues Bruno, Lopes-Ramos Camila, Nilsson Daniel, Knittel Thiago Leite, Ribeiro Castro Pollyana, Fernandes Mariane Font, Dos Santos Martins Falviano, Parmigiani Raphael Bessa, Silveira Leonardo Reis, Carvalho Hernandes F, Auwerx Johan, Vinolo Marco Aurelio R, Boucher Jeremie, Mori Marcelo A (2020) Sci Adv

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 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).

Bioblast editor: Plangger M O2k-Network Lab: CH Lausanne Auwerx J

Labels: MiParea: Respiration, nDNA;cell genetics, Genetic knockout;overexpression, Pharmacology;toxicology  Pathology: Obesity 

Organism: Mouse  Tissue;cell: Fat  Preparation: Intact cells 

Coupling state: LEAK, ROUTINE, ET  Pathway: ROX  HRR: Oxygraph-2k