Abstract

The sphingolipid metabolic pathway is initiated by the incorporation of palmitoyl CoA, derivative of fatty acids, and ultimately provides substrates for phospholipid metabolism. 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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIADK056018-04
Application #
8148858
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2010
Total Cost
$345,599
Indirect Cost

  Institution

Name
National Institute of Diabetes and Digestive and Kidney Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Xu, Lingyan; Ma, Xinran; Verma, Narendra Kumar et al. (2018) Ablation of PPAR? in subcutaneous fat exacerbates age-associated obesity and metabolic decline. Aging Cell 17:
Alexaki, Aikaterini; Clarke, Benjamin A; Gavrilova, Oksana et al. (2017) De Novo Sphingolipid Biosynthesis Is Required for Adipocyte Survival and Metabolic Homeostasis. J Biol Chem 292:3929-3939
Taguchi, Yoshimitsu; Allende, Maria L; Mizukami, Hiroki et al. (2016) Sphingosine-1-phosphate Phosphatase 2 Regulates Pancreatic Islet ?-Cell Endoplasmic Reticulum Stress and Proliferation. J Biol Chem 291:12029-38
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
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
Blaho, Victoria A; Galvani, Sylvain; Engelbrecht, Eric et al. (2015) HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation. Nature 523:342-6
Weth, Daniela; Benetti, Camilla; Rauch, Caroline et al. (2015) Activated platelets release sphingosine 1-phosphate and induce hypersensitivity to noxious heat stimuli in vivo. Front Neurosci 9:140
Proia, Richard L; Hla, Timothy (2015) Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest 125:1379-87
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
Allende, Maria Laura; Proia, Richard L (2014) Simplifying complexity: genetically resculpting glycosphingolipid synthesis pathways in mice to reveal function. Glycoconj J 31:613-22

Showing the most recent 10 out of 21 publications