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Type: Journal article
Title: Overexpression of sphingosine kinase 1 prevents ceramide accumulation and ameliorates muscle insulin resistance in high-fat diet-fed mice
Author: Bruce, C.
Risis, S.
Babb, J.
Yang, C.
Kowalski, G.
Selathurai, A.
Lee-Young, R.
Weir, J.
Yoshioka, K.
Takuwa, Y.
Meikle, P.
Pitson, S.
Febbraio, M.
Citation: Diabetes, 2012; 61(12):3148-3155
Publisher: American Diabetes Association
Issue Date: 2012
ISSN: 0012-1797
Statement of
Clinton R. Bruce, Steve Risis, Joanne R. Babb, Christine Yang, Greg M. Kowalski, Ahrathy Selathurai, Robert S. Lee-Young, Jacquelyn M. Weir, Kazuaki Yoshioka, Yoh Takuwa, Peter J. Meikle, Stuart M. Pitson, and Mark A. Febbraio
Abstract: The sphingolipids sphingosine-1-phosphate (S1P) and ceramide are important bioactive lipids with many cellular effects. Intracellular ceramide accumulation causes insulin resistance, but sphingosine kinase 1 (SphK1) prevents ceramide accumulation, in part, by promoting its metabolism into S1P. Despite this, the role of SphK1 in regulating insulin action has been largely overlooked. Transgenic (Tg) mice that overexpress SphK1 were fed a standard chow or high-fat diet (HFD) for 6 weeks before undergoing several metabolic analyses. SphK1 Tg mice fed an HFD displayed increased SphK activity in skeletal muscle, which was associated with an attenuated intramuscular ceramide accumulation compared with wild-type (WT) littermates. This was associated with a concomitant reduction in the phosphorylation of c-jun amino-terminal kinase, a serine threonine kinase associated with insulin resistance. Accordingly, skeletal muscle and whole-body insulin sensitivity were improved in SphK1 Tg, compared with WT mice, when fed an HFD. We have identified that the enzyme SphK1 is an important regulator of lipid partitioning and insulin action in skeletal muscle under conditions of increased lipid supply.
Keywords: Muscle, Skeletal
Rights: © 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See -nc-nd/3.0/ for details.
RMID: 0030028781
DOI: 10.2337/db12-0029
Grant ID:
Appears in Collections:Medicine publications

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