Ceramide lipids have been implicated in the regulation of metabolic physiology. In particular, increased levels of the C-18 ceramide in muscle have been associated with impaired insulin action and increased visceral fat. Turner et al. identify the first isoform-selective ceramide synthase (CerS) inhibitor, P053, which specifically and potently targets CerS1 (responsible for C-18 ceramide formation), reducing C-18 ceramide levels in cultured cells and mouse skeletal muscle. In mice fed a high-fat diet, daily oral treatment with P053 promoted skeletal muscle fatty acid oxidation and reduced whole-body fat accumulation, without effects on insulin resistance.
References
Turner, N. et al. A selective inhibitor of ceramide synthase 1 reveals a novel role in fat metabolism. Nat. Commun. 9, 3165 (2018)10.1038/s41467-018-05613-7
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Crunkhorn, S. Blocking ceramide formation. Nat Rev Drug Discov 17, 708 (2018). https://doi.org/10.1038/nrd.2018.173
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DOI: https://doi.org/10.1038/nrd.2018.173