Lipidome-wide 13 C flux analysis: a novel tool to estimate the turnover of lipids in organisms and cultures.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0376606 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1539-7262 (Electronic) Linking ISSN: 00222275 NLM ISO Abbreviation: J Lipid Res Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York] : Elsevier
      Original Publication: Memphis, Lipid Research, inc.
    • Subject Terms:
      Isotope Labeling* ; Lipid Metabolism* ; Lipidomics*; Drosophila melanogaster/*metabolism ; Lipids/*analysis; Animals ; Carbon Isotopes ; Chromatography, Liquid ; Tandem Mass Spectrometry
    • Abstract:
      Lipid metabolism plays an important role in the regulation of cellular homeostasis. However, because it is difficult to measure the actual rates of synthesis and degradation of individual lipid species, lipid compositions are often used as a surrogate to evaluate lipid metabolism even though they provide only static snapshots of the lipodome. Here, we designed a simple method to determine the turnover rate of phospholipid and acylglycerol species based on the incorporation of 13 C 6 -glucose combined with LC-MS/MS. We labeled adult Drosophila melanogaster with 13 C 6 -glucose that incorporates into the entire lipidome, derived kinetic parameters from mass spectra, and studied effects of deletion of CG6718, the fly homolog of the calcium-independent phospholipase A2β, on lipid metabolism. Although 13 C 6 -glucose gave rise to a complex pattern of 13 C incorporation, we were able to identify discrete isotopomers in which 13 C atoms were confined to the glycerol group. With these isotopomers, we calculated turnover rate constants, half-life times, and fluxes of the glycerol backbone of multiple lipid species. To perform these calculations, we estimated the fraction of labeled molecules in glycerol-3-phosphate, the lipid precursor, by mass isotopomer distribution analysis of the spectra of phosphatidylglycerol. When we applied this method to D. melanogaster , we found a range of lipid half-lives from 2 to 200 days, demonstrated tissue-specific fluxes of individual lipid species, and identified a novel function of CG6718 in triacylglycerol metabolism. This method provides fluxomics-type data with significant potential to improve the understanding of complex lipid regulation in a variety of research models.
      (Copyright © 2020 Schlame et al.)
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    • Grant Information:
      R01 GM115593 United States GM NIGMS NIH HHS; S10 OD023659 United States OD NIH HHS
    • Contributed Indexing:
      Keywords: genes in lipid dysfunction; lipid metabolism; mass spectrometry; phospholipids/metabolism; stable isotope tracers
    • Accession Number:
      0 (Carbon Isotopes)
      0 (Lipids)
    • Publication Date:
      Date Created: 20191113 Date Completed: 20210208 Latest Revision: 20240329
    • Publication Date:
      20240329
    • Accession Number:
      PMC6939592
    • Accession Number:
      10.1194/jlr.D119000318
    • Accession Number:
      31712250