Lipids play a central role in cellular function and disease. The scope of lipid involvement in cellular function has only recently been recognized to extend well beyond its established roles in energy metabolism and membrane structure. Lipids are an extensive group of small, amphipathic molecules comprised of 1,000's of distinct molecular species possessing many similar chemical and physical properties. The metabolic pathways that deal with lipids are complex and intertwined. Developing an integrated metabolomic system capable of characterizing the global changes in lipid metabolites ("lipidomics") is a daunting task but one that it is important to undertake in light of the significant returns produced by the global approaches of genomics, transcriptomics and proteomics. Our consortium has developed a Lipid Metabolites and Pathways Strategy, termed LIPID MAPS that applies an integrated approach to the study of lipidomics. One goal of LIPID MAPS for the renewal grant period is to employ the technology that we have developed to measure the lipidomes of primary and immortalized mouse macrophages subjected to different perturbations to advance our mechanistic understanding of biochemical pathways and the regulation of lipid metabolism. Another goal is to conduct lipidomic analyses of mouse cells and tissues to provide new understanding of how different lipid pathways interact under normal and pathological conditions in established models of disease. By continuing to employ a rigorously maintained set of common biological, biochemical, and analytical technologies in each of the consortium laboratories, and by using an extensive informatics infrastructure, we will be able to integrate and analyze the extensive data that will be generated by this large scale collaborative project during the renewal period. We plan to generate "metabolomic networks and roadmaps" that will define how all of the lipid components of a cell interact during biosynthesis, degradation, and signaling. All of this information will be shared with the entire research community and should serve as a paradigm for metabolomics research and systems biology integration. LIPID MAPS will also contribute to drug development since lipids play critical roles in numerous diseases, especially inflammatory processes and the metabolic syndrome underlying atherosclerosis and diabetes.

Public Health Relevance

Lipids play important roles in normal physiological function and in many diseases. Determining how the levels of these compounds change during the course of disease and in response to various pharmacological interventions will increase our understanding of disease processes and enhance our ability to develop effective new treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54GM069338-10
Application #
8337359
Study Section
Special Emphasis Panel (ZGM1-CBB-5 (GL))
Program Officer
Chin, Jean
Project Start
2003-08-12
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
10
Fiscal Year
2012
Total Cost
$7,153,421
Indirect Cost
$1,446,648
Name
University of California San Diego
Department
Pharmacology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Astarita, Giuseppe; Kendall, Alexandra C; Dennis, Edward A et al. (2015) Targeted lipidomic strategies for oxygenated metabolites of polyunsaturated fatty acids. Biochim Biophys Acta 1851:456-68
Corser-Jensen, Chelsea E; Goodell, Dayton J; Freund, Ronald K et al. (2014) Blocking leukotriene synthesis attenuates the pathophysiology of traumatic brain injury and associated cognitive deficits. Exp Neurol 256:7-16
Guan, Ziqiang; Katzianer, David; Zhu, Jun et al. (2014) Clostridium difficile contains plasmalogen species of phospholipids and glycolipids. Biochim Biophys Acta 1842:1353-9
Wang, Yan; Armando, Aaron M; Quehenberger, Oswald et al. (2014) Comprehensive ultra-performance liquid chromatographic separation and mass spectrometric analysis of eicosanoid metabolites in human samples. J Chromatogr A 1359:60-9
Ren, Jihui; Pei-Chen Lin, Coney; Pathak, Manish C et al. (2014) A phosphatidylinositol transfer protein integrates phosphoinositide signaling with lipid droplet metabolism to regulate a developmental program of nutrient stress-induced membrane biogenesis. Mol Biol Cell 25:712-27
Baldan, Angel; Gonen, Ayelet; Choung, Christina et al. (2014) ABCG1 is required for pulmonary B-1 B cell and natural antibody homeostasis. J Immunol 193:5637-48
Currais, Antonio; Prior, Marguerite; Dargusch, Richard et al. (2014) Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer's disease transgenic mice. Aging Cell 13:379-90
Jiao, Jing; Mikulec, Carol; Ishikawa, Tomo-o et al. (2014) Cell-type-specific roles for COX-2 in UVB-induced skin cancer. Carcinogenesis 35:1310-9
Masnadi-Shirazi, Maryam; Maurya, Mano Ram; Subramaniam, Shankar (2014) Time-varying causal inference from phosphoproteomic measurements in macrophage cells. IEEE Trans Biomed Circuits Syst 8:74-86
Norris, Paul C; Gosselin, David; Reichart, Donna et al. (2014) Phospholipase A2 regulates eicosanoid class switching during inflammasome activation. Proc Natl Acad Sci U S A 111:12746-51

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