title: Stable isotope analysis of dynamic lipidomics.
abstract: Metabolic pathway flux is a fundamental element of biological activity, which can be quantified using a variety of mass spectrometric techniques to monitor incorporation of stable isotope-labelled substrates into metabolic products. This article contrasts developments in electrospray ionisation mass spectrometry (ESI-MS) for the measurement of lipid metabolism with more established gas chromatography mass spectrometry and isotope ratio mass spectrometry methodologies. ESI-MS combined with diagnostic tandem MS/MS scans permits the sensitive and specific analysis of stable isotope-labelled substrates into intact lipid molecular species without the requirement for lipid hydrolysis and derivatisation. Such dynamic lipidomic methodologies using non-toxic stable isotopes can be readily applied to quantify lipid metabolic fluxes in clinical and metabolic studies in vivo. However, a significant current limitation is the absence of appropriate software to generate kinetic models of substrate incorporation into multiple products in the time domain. Finally, we discuss the future potential of stable isotope-mass spectrometry imaging to quantify the location as well as the extent of lipid synthesis. This article is part of a Special Issue entitled: BBALIP_Lipidomics Opinion Articles edited by Sepp Kohlwein.
authors.affiliation: Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Joost
authors.initials: J
authors.lastname: Brandsma
authors.affiliation: The Francis Crick Institute, 1 Midland Road, London, United Kingdom.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Bailey
authors.affiliation: Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute of Health Research Biomedical Research Unit in Respiratory Medicine, University Hospitals Southampton NHS Foundation Trust, United Kingdom.
authors.forename: Grielof
authors.initials: G
authors.lastname: Koster
authors.affiliation: The Francis Crick Institute, 1 Midland Road, London, United Kingdom.
authors.forename: Alex P
authors.initials: AP
authors.lastname: Gould
authors.affiliation: Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom. Electronic address: adp@soton.ac.uk.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Postle
mesh_terms: D000818:Animals; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D007554:Isotopes / Q000737:chemistry*; D050356:Lipid Metabolism / Q000502:physiology*; D008055:Lipids / Q000737:chemistry*; D053858:Metabolic Networks and Pathways / Q000502:physiology; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D007554:Isotopes; D008055:Lipids
keywords: Dynamic lipidomics; Lipid metabolism; Mass spectrometry; Stable isotopes