title: Comparative Lipidomics of Caenorhabditis elegans Metabolic Disease Models by SWATH Non-Targeted Tandem Mass Spectrometry.
abstract: Tandem mass spectrometry (MS/MS) with Sequential Window Acquisition of all Theoretical (SWATH) mass spectra generates a comprehensive archive of lipid species within an extract for retrospective, quantitative MS/MS analysis. Here we apply this new technology in Caenorhabditis elegans (C. elegans) to identify potential lipid mediators and pathways. The DAF-1 type I TGF-β and DAF-2 insulin receptors transmit endocrine signals that couple metabolic status to fertility and lifespan. Mutations in daf-1 and daf-2 reduce prostaglandin-endoperoxide synthase (i.e., Cox)-independent prostaglandin synthesis, increase triacylglyceride storage, and alter transcription of numerous lipid metabolism genes. However, the extent to which DAF-1 and DAF-2 signaling modulate lipid metabolism and the underlying mechanisms are not well understood. MS/MSALL with SWATH analysis across the groups identified significant changes in numerous lipids, including specific triacylglycerols, diacylglycerols, and phosphatidylinositols. Examples are provided, using retrospective neutral loss and precursor ion scans as well as MS/MS spectra, to help identify annotated lipids and search libraries for lipids of interest. As proof of principle, we used comparative lipidomics to investigate the prostaglandin metabolism pathway. SWATH data support an unanticipated model: Cox-independent prostaglandin synthesis may involve lysophosphatidylcholine and other lyso glycerophospholipids. This study showcases the power of comprehensive, retrospectively searchable lipid archives as a systems approach for biological discovery in genetic animal models.
authors.affiliation: Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. jprasain@uab.edu.|Targeted Metabolomics and Proteomics Laboratory, University of Alabama at Birmingham, Birmingham, AL 35294, USA. jprasain@uab.edu.
authors.forename: Jeevan K
authors.initials: JK
authors.lastname: Prasain
authors.affiliation: Targeted Metabolomics and Proteomics Laboratory, University of Alabama at Birmingham, Birmingham, AL 35294, USA. empy1977@uab.edu.
authors.forename: Landon
authors.initials: L
authors.lastname: Wilson
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. hdhoang@uab.edu.
authors.forename: Hieu D
authors.initials: HD
authors.lastname: Hoang
authors.affiliation: Targeted Metabolomics and Proteomics Laboratory, University of Alabama at Birmingham, Birmingham, AL 35294, USA. raymoore@uab.edu.
authors.forename: Ray
authors.initials: R
authors.lastname: Moore
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. mamiller@uab.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Miller
keywords: Caenorhabditis elegans; MS/MSALL; SWATH; arachidonic acid; cyclooxygenase; insulin; lipidomics; prostaglandin; tandem mass spectrometry; triglycerides