A selective inhibitor of ceramide synthase 1 reveals a novel role in fat metabolism.
Full text not available from this repository.Item Type: | Article |
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Status: | Published |
Official URL: | https://doi.org/10.1038/s41467-018-05613-7 |
Journal or Publication Title: | Nature Communications |
Volume: | 9 |
Number: | 1 |
Date: | 2018 |
Divisions: | Lipid Metabolism and Neurochemistry |
Depositing User: | General Admin |
Identification Number: | 10.1038/s41467-018-05613-7 |
ISSN: | 2041-1723 |
Date Deposited: | 03 Jan 2021 22:47 |
Abstract: | Specific forms of the lipid ceramide, synthesized by the ceramide synthase enzyme family, are believed to regulate metabolic physiology. Genetic mouse models have established C16 ceramide as a driver of insulin resistance in liver and adipose tissue. C18 ceramide, synthesized by ceramide synthase 1 (CerS1), is abundant in skeletal muscle and suggested to promote insulin resistance in humans. We herein describe the first isoform-specific ceramide synthase inhibitor, P053, which inhibits CerS1 with nanomolar potency. Lipidomic profiling shows that P053 is highly selective for CerS1. Daily P053 administration to mice fed a high-fat diet (HFD) increases fatty acid oxidation in skeletal muscle and impedes increases in muscle triglycerides and adiposity, but does not protect against HFD-induced insulin resistance. Our inhibitor therefore allowed us to define a role for CerS1 as an endogenous inhibitor of mitochondrial fatty acid oxidation in muscle and regulator of whole-body adiposity. |
Creators: | Creators Email Turner, Nigel UNSPECIFIED Lim, Xin Ying UNSPECIFIED Toop, Hamish D. UNSPECIFIED Osborne, Brenna UNSPECIFIED Brandon, Amanda E. UNSPECIFIED Taylor, Elysha N. UNSPECIFIED Fiveash, Corrine E. UNSPECIFIED Govindaraju, Hemna UNSPECIFIED Teo, Jonathan D. UNSPECIFIED McEwen, Holly P. UNSPECIFIED Couttas, Timothy A. UNSPECIFIED Butler, Stephen M. UNSPECIFIED Das, Abhirup UNSPECIFIED Kowalski, Greg M. UNSPECIFIED Bruce, Clinton R. UNSPECIFIED Hoehn, Kyle L. UNSPECIFIED Fath, Thomas UNSPECIFIED Schmitz-Peiffer, Carsten UNSPECIFIED Cooney, Gregory J. UNSPECIFIED Montgomery, Magdalene K. UNSPECIFIED Morris, Jonathan C. UNSPECIFIED Don, Anthony S. UNSPECIFIED |
Last Modified: | 03 Jan 2021 22:47 |
URI: | https://eprints.centenary.org.au/id/eprint/524 |
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