New insights into lipid and fatty acid metabolism via stable isotopes

Dynamic processes are of great interest in the study of lipid and fatty acid metabolism. Their in vivo investigation is now possible with the use of stable isotope tracers and the available sensitive analytical technology. We present some examples demonstrating the assessment of lipid oxidation as well as modulating factors by analysis of the tracer appearance in breath CO2 by isotope ratio mass spectrometry (IRMS). In a child with severe hyper triglyceridaemia due to decreased cleavage of chylomicrons, medium-chain triglycerides were oxidised normally, whereas utilisation of long-chain triglycerides was severely disturbed. In another patient with primary carnitine deficiency, the beneficial effect of carnitine supplementation on fat oxidation could be demonstrated. In combination with gas chromatography, the high sensitivity of IRMS may be used for the detection of tracer materials in various plasma metabolites. In a pilot study, we applied U-C-13 labelled linoleic and alpha-linolenic acids to infants aged 2 weeks and 11 months, respectively. In these subjects, we could show a relative decrease of the conversion of these essential fatty acids to their longer chain polyunsaturated derivatives with age. The ability of term infants aged 19 days to convert linoleic into arachidonic acid was evaluated by using small natural differences in C-13 abundance between different foods. Stable isotopes are also suitable for elucidation of new metabolic pathways. As an example, we could show in rats that linoleic and alpha-linolenic acids, which are usually considered to be essential substrates, can be synthesized endogenously from C16 precursors.