A selective inhibitor of ceramide synthase 1 reveals a novel role in fat metabolism

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Standard

A selective inhibitor of ceramide synthase 1 reveals a novel role in fat metabolism. / Turner, Nigel; Lim, Xin Ying; Toop, Hamish D.; Osborne, Brenna; Brandon, Amanda E.; Taylor, Elysha N.; Fiveash, Corrine E.; Govindaraju, Hemna; Teo, Jonathan D.; McEwen, Holly P.; Couttas, Timothy A.; Butler, Stephen M.; Das, Abhirup; Kowalski, Greg M.; Bruce, Clinton R.; Hoehn, Kyle L.; Fath, Thomas; Schmitz-Peiffer, Carsten; Cooney, Gregory J.; Montgomery, Magdalene K.; Morris, Jonathan C.; Don, Anthony S.

I: Nature Communications, Bind 9, 3165, 12.2018.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Turner, N, Lim, XY, Toop, HD, Osborne, B, Brandon, AE, Taylor, EN, Fiveash, CE, Govindaraju, H, Teo, JD, McEwen, HP, Couttas, TA, Butler, SM, Das, A, Kowalski, GM, Bruce, CR, Hoehn, KL, Fath, T, Schmitz-Peiffer, C, Cooney, GJ, Montgomery, MK, Morris, JC & Don, AS 2018, 'A selective inhibitor of ceramide synthase 1 reveals a novel role in fat metabolism', Nature Communications, bind 9, 3165. https://doi.org/10.1038/s41467-018-05613-7

APA

Turner, N., Lim, X. Y., Toop, H. D., Osborne, B., Brandon, A. E., Taylor, E. N., Fiveash, C. E., Govindaraju, H., Teo, J. D., McEwen, H. P., Couttas, T. A., Butler, S. M., Das, A., Kowalski, G. M., Bruce, C. R., Hoehn, K. L., Fath, T., Schmitz-Peiffer, C., Cooney, G. J., ... Don, A. S. (2018). A selective inhibitor of ceramide synthase 1 reveals a novel role in fat metabolism. Nature Communications, 9, [3165]. https://doi.org/10.1038/s41467-018-05613-7

Vancouver

Turner N, Lim XY, Toop HD, Osborne B, Brandon AE, Taylor EN o.a. A selective inhibitor of ceramide synthase 1 reveals a novel role in fat metabolism. Nature Communications. 2018 dec.;9. 3165. https://doi.org/10.1038/s41467-018-05613-7

Author

Turner, Nigel ; Lim, Xin Ying ; Toop, Hamish D. ; Osborne, Brenna ; Brandon, Amanda E. ; Taylor, Elysha N. ; Fiveash, Corrine E. ; Govindaraju, Hemna ; Teo, Jonathan D. ; McEwen, Holly P. ; Couttas, Timothy A. ; Butler, Stephen M. ; Das, Abhirup ; Kowalski, Greg M. ; Bruce, Clinton R. ; Hoehn, Kyle L. ; Fath, Thomas ; Schmitz-Peiffer, Carsten ; Cooney, Gregory J. ; Montgomery, Magdalene K. ; Morris, Jonathan C. ; Don, Anthony S. / A selective inhibitor of ceramide synthase 1 reveals a novel role in fat metabolism. I: Nature Communications. 2018 ; Bind 9.

Bibtex

@article{7d58531bea8a48288de73bc648ddfd1d,
title = "A selective inhibitor of ceramide synthase 1 reveals a novel role in fat metabolism",
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.",
author = "Nigel Turner and Lim, {Xin Ying} and Toop, {Hamish D.} and Brenna Osborne and Brandon, {Amanda E.} and Taylor, {Elysha N.} and Fiveash, {Corrine E.} and Hemna Govindaraju and Teo, {Jonathan D.} and McEwen, {Holly P.} and Couttas, {Timothy A.} and Butler, {Stephen M.} and Abhirup Das and Kowalski, {Greg M.} and Bruce, {Clinton R.} and Hoehn, {Kyle L.} and Thomas Fath and Carsten Schmitz-Peiffer and Cooney, {Gregory J.} and Montgomery, {Magdalene K.} and Morris, {Jonathan C.} and Don, {Anthony S.}",
year = "2018",
month = dec,
doi = "10.1038/s41467-018-05613-7",
language = "English",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - A selective inhibitor of ceramide synthase 1 reveals a novel role in fat metabolism

AU - Turner, Nigel

AU - Lim, Xin Ying

AU - Toop, Hamish D.

AU - Osborne, Brenna

AU - Brandon, Amanda E.

AU - Taylor, Elysha N.

AU - Fiveash, Corrine E.

AU - Govindaraju, Hemna

AU - Teo, Jonathan D.

AU - McEwen, Holly P.

AU - Couttas, Timothy A.

AU - Butler, Stephen M.

AU - Das, Abhirup

AU - Kowalski, Greg M.

AU - Bruce, Clinton R.

AU - Hoehn, Kyle L.

AU - Fath, Thomas

AU - Schmitz-Peiffer, Carsten

AU - Cooney, Gregory J.

AU - Montgomery, Magdalene K.

AU - Morris, Jonathan C.

AU - Don, Anthony S.

PY - 2018/12

Y1 - 2018/12

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-018-05613-7

DO - 10.1038/s41467-018-05613-7

M3 - Journal article

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 3165

ER -

ID: 291673358