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Metabolites 2015, 5(4), 677-696; doi:10.3390/metabo5040677

Comparative Lipidomics of Caenorhabditis elegans Metabolic Disease Models by SWATH Non-Targeted Tandem Mass Spectrometry

1
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
2
Targeted Metabolomics and Proteomics Laboratory, University of Alabama at Birmingham, Birmingham, AL 35294, USA
3
Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Peter Meikle
Received: 30 September 2015 / Revised: 29 October 2015 / Accepted: 4 November 2015 / Published: 11 November 2015
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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. View Full-Text
Keywords: Caenorhabditis elegans; lipidomics; SWATH; tandem mass spectrometry; insulin; prostaglandin; cyclooxygenase; triglycerides; arachidonic acid; MS/MSALL Caenorhabditis elegans; lipidomics; SWATH; tandem mass spectrometry; insulin; prostaglandin; cyclooxygenase; triglycerides; arachidonic acid; MS/MSALL
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Prasain, J.K.; Wilson, L.; Hoang, H.D.; Moore, R.; Miller, M.A. Comparative Lipidomics of Caenorhabditis elegans Metabolic Disease Models by SWATH Non-Targeted Tandem Mass Spectrometry. Metabolites 2015, 5, 677-696.

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