Overexpression of Sphingosine Kinase 1 Prevents Ceramide Accumulation and Ameliorates Muscle Insulin Resistance in High-Fat Diet-Fed Mice
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, Mark A Febbraio
DIABETES | AMER DIABETES ASSOC | Published : 2012
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 w..View full abstract
Awarded by NHMRC
Awarded by Grants-in-Aid for Scientific Research
This work was supported by NHMRC Project Grant 526608 to C.R.B. and the Victorian Government Operational Infrastructure Support Program. C.R.B. is a Career Development Fellow. S.M.P. and P.J.M. are Senior Research Fellows, and M.A.F. is a Senior Principal Research Fellow of the NHMRC.