Application of new methods and analytical approaches to research on polyunsaturated fatty acid homeostasis

Abstract

New methods and analytical approaches are important to challenge and/or validate established beliefs in any field including the metabolism of polyunsaturated fatty acids (PUFA; polyunsaturates). Four methods that have recently been applied toward obtaining a better understanding of the homeostasis of PUFA include the following: whole-body fatty acid balance analysis, magnetic resonance imaging (MRI), 13C nuclear magnetic resonance (NMR) spectroscopy, and gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Whole-body balance studies permit the measurement of both the percentage of oxidation of linoleate and alpha-linolenate and their conversion to long-chain PUFA. This method has shown that beta-oxidation to CO2 is normally the predominant metabolic fate of linoleate and alpha-linolenate. Furthermore, models of experimental undernutrition in both humans and animals show that beta-oxidation of linoleate and alpha-linolenate markedly exceeds their intake, despite theoretically sufficient intake of linoleate or alpha-linolenate. Preliminary results suggest that by using MRI to measure body fat content, indirect whole-body linoleate balance can be done in living humans. 13C NMR spectroscopy provided unexpected evidence that linoleate and alpha-linolenate were metabolized into lipids synthesized de novo, an observation later quantified by tracer mass balance done using GC-C-IRMS. This latter method showed that within 48 h of dosing with 13C-alpha-linolenate, >80% underwent beta-oxidation to CO2 by suckling rats, whereas 8-9% was converted to newly synthesized lipids and <1 % to docosahexaenoate. Further application of these recently developed methods in different models should clarify the emerging importance of beta-oxidation and carbon recycling in PUFA homeostasis in mammals including humans.