Session:: Brain Fatty Acid Metabolism and Signaling in Inflammation
Novel methods using natural abundance carbon isotope ratios to study the turnover and metabolism of fatty acids reveals how docosahexaenoic acid regulates its own synthesis
Assistant Professor University of Toronto Toronto, Ontario, Canada
Abstract: The brain and retina are especially enriched in docosahexaenoic acid (DHA, 22:6n-3), a polyunsaturated fatty acid that participates in signal transduction either directly or in part upon conversion to bioactive lipid mediators. DHA tissue levels are regulated by diet where DHA can either be consumed preformed or synthesized enzymatically via a series of desaturation and elongation reactions from shorter chain dietary precursors, especially alpha-linolenic acid (ALA. 18:3n-3). Furthermore, dietary DHA not only increases blood and tissue levels of DHA, but also eicosapentaenoic acid (EPA, 20:5n-3). It is generally believed that this increase in EPA is due to DHA retroconversion to EPA i.e. the removal of two carbons and a double bond. However, by using compound specific isotope analysis via gas chromatography coupled to high precision isotope ratio mass spectrometry we observed, in both rodents and humans, that the isotopic signature of elevated EPA upon DHA consumption did not match DHA, but rather ALA suggesting EPA accumulation was synthesis from ALA identifying a potential feedback inhibition step. Herein we will describe further data supporting that DHA regulates its own synthesis via inhibition of elongases 2 and 5. The potential significance of DHA feedback inhibition will also be discussed.