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
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Taguchi, Yoshimitsu; Allende, Maria L; Mizukami, Hiroki et al. (2016) Sphingosine-1-phosphate Phosphatase 2 Regulates Pancreatic Islet β-Cell Endoplasmic Reticulum Stress and Proliferation. J Biol Chem 291:12029-38
Proia, Richard L; Hla, Timothy (2015) Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest 125:1379-87
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Galvani, Sylvain; Sanson, Marie; Blaho, Victoria A et al. (2015) HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation. Sci Signal 8:ra79
Gupta, Sita D; Gable, Kenneth; Alexaki, Aikaterini et al. (2015) Expression of the ORMDLS, modulators of serine palmitoyltransferase, is regulated by sphingolipids in mammalian cells. J Biol Chem 290:90-8
Tabeling, Christoph; Yu, Hanpo; Wang, Liming et al. (2015) CFTR and sphingolipids mediate hypoxic pulmonary vasoconstriction. Proc Natl Acad Sci U S A 112:E1614-23
Alexaki, Aikaterini; Gupta, Sita D; Majumder, Saurav et al. (2014) Autophagy regulates sphingolipid levels in the liver. J Lipid Res 55:2521-31
Allende, Maria Laura; Proia, Richard L (2014) Simplifying complexity: genetically resculpting glycosphingolipid synthesis pathways in mice to reveal function. Glycoconj J 31:613-22
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

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