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.
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.
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