The sphingolipid metabolic pathway is initiated by the incorporation of palmitoyl CoA, derivative of fatty acids, and ultimately provides substrates for the synthesis of other lipids. Thus the sphingolipid metabolic pathway is highly integrated with other dietary and structural lipid metabolic pathways. Furthermore, the sphingolipid metabolites themselves are bioactive and alter cell metabolism via signaling pathways. We have developed, and continue to develop genetically altered mice with modified expression of key sphingolipid enzyme activities in order to study the role of the pathway in metabolism including their role in diabetes and obesity.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$599,767
Indirect Cost
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State
Country
Zip Code
Olivera, Ana; Allende, Maria Laura; Proia, Richard L (2013) Shaping the landscape: metabolic regulation of S1P gradients. Biochim Biophys Acta 1831:193-202
Allende, Maria L; Sipe, Laura M; Tuymetova, Galina et al. (2013) Sphingosine-1-phosphate phosphatase 1 regulates keratinocyte differentiation and epidermal homeostasis. J Biol Chem 288:18381-91
Hagen, Nadine; Van Veldhoven, Paul P; Proia, Richard L et al. (2009) Subcellular origin of sphingosine 1-phosphate is essential for its toxic effect in lyase-deficient neurons. J Biol Chem 284:11346-53