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

Andréa Livia RochaTanes Iamamura de LimaGerson Profeta de SouzaRenan Oliveira CorrêaDanilo Lopes FerrucciBruno RodriguesCamila M Lopes-RamosDaniel NilssonThiago Leite KnittelPollyana Ribeiro CastroMariane Font FernandesFlaviano Dos Santos MartinsRaphael Bessa ParmigianiLeonardo Reis SilveiraHernandes F CarvalhoJohan AuwerxMarco Aurélio Ramirez VinoloJeremie BoucherMarcelo Alves da Silva Mori
Published in: Science advances (2020)
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.
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