Research ArticleMetabolism

Identification of entacapone as a chemical inhibitor of FTO mediating metabolic regulation through FOXO1

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Science Translational Medicine  17 Apr 2019:
Vol. 11, Issue 488, eaau7116
DOI: 10.1126/scitranslmed.aau7116

The skinny on FTO

Although the fat mass and obesity-associated gene FTO has been linked to genetic risk of obesity, the mRNA demethylase that it encodes has proven difficult to therapeutically target. From a screen of approved drugs, Peng et al. identified entacapone, a catechol-O-methyltransferase inhibitor used in the treatment of Parkinson’s disease, as an inhibitor of FTO. In vivo administration of entacapone improved body weight and glucose tolerance and increased adipose thermogenesis in mice, which the authors tied to decreased FTO-catalyzed m6A demethylation of FOXO1 mRNA. Further studies will need to confirm the repurposing potential of entacapone for obesity or metabolic disease in humans.

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