A metabolomic strategy defines the regulation of lipid content and global metabolism by Δ9 desaturases in Caenorhabditis elegans
File(s)
Author(s)
Type
Journal Article
Abstract
BACKGROUND: Caenorhabditis elegans provides a genetically tractable model organism to investigate the network of genes involved in fat metabolism and how regulation is perturbed to produce the complex phenotype of obesity. C. elegans possess the full range of desaturases, including the Δ9 desaturases expressed by fat-5, fat-6 and fat-7. They regulate the biosynthesis of monounsaturated fatty acids, used for the synthesis of lipids including phospholipids, triglycerides and cholesteryl esters. RESULTS: Liquid chromatography mass spectrometry (LC-MS), gas chromatography mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy were used to define the metabolome of all the possible knock-outs for the Δ9 desaturases, including for the first time intact lipids. Despite the genes having similar enzymatic roles, excellent discrimination was achievable for all single and viable double mutants highlighting the distinctive roles of fat-6 and fat-7, both expressing steroyl-CoA desaturases. The metabolomic changes extend to aqueous metabolites demonstrating the influence Δ9 desaturases have on regulating global metabolism and highlighting how comprehensive metabolomics is more discriminatory than classically used dyes for fat staining. CONCLUSIONS: The propagation of metabolic changes across the network of metabolism demonstrates that modification of the Δ9 desaturases places C.elegans into a catabolic state compared with wildtype controls.
Date Issued
2012-01-20
Date Acceptance
2012-01-20
Citation
BMC Genomics, 2012, 13
ISSN
1471-2164
Publisher
BioMed Central
Journal / Book Title
BMC Genomics
Volume
13
Copyright Statement
© 2012 Castro et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/22264337
PII: 1471-2164-13-36
Subjects
Animals
Caenorhabditis elegans
Chromatography, High Pressure Liquid
Fatty Acids
Gas Chromatography-Mass Spectrometry
Gene Knockout Techniques
Lipids
Magnetic Resonance Spectroscopy
Mass Spectrometry
Metabolome
Stearoyl-CoA Desaturase
Publication Status
Published
Coverage Spatial
England
Article Number
ARTN 36