title: Quantifying conversion of linoleic to arachidonic and other n-6 polyunsaturated fatty acids in unanesthetized rats.
abstract: Isotope feeding studies report a wide range of conversion fractions of dietary shorter-chain polyunsaturated fatty acids (PUFAs) to long-chain PUFAs, which limits assessing nutritional requirements and organ effects of arachidonic (AA, 20:4n-6) and docosahexaenoic (DHA, 22:6n-3) acids. In this study, whole-body (largely liver) steady-state conversion coefficients and rates of circulating unesterified linoleic acid (LA, 18:2n-6) to esterified AA and other elongated n-6 PUFAs were quantified directly using operational equations, in unanesthetized adult rats on a high-DHA but AA-free diet, using 2 h of intravenous [U-(13)C]LA infusion. Unesterified LA was converted to esterified LA in plasma at a greater rate than to esterified gamma-linolenic (gamma-LNA, 18:3n-6), eicosatrienoic acid (ETA, 20:3n-6), or AA. The steady-state whole-body synthesis-secretion (conversion) coefficient k*(i) to AA equaled 5.4 x 10(-3) min(-1), while the conversion rate (coefficient x concentration) equaled 16.1 micromol/day. This rate exceeds the reported brain AA consumption rate by 27-fold. As brain and heart cannot synthesize significant AA from circulating LA, liver synthesis is necessary to maintain their homeostatic AA concentrations in the absence of dietary AA. The heavy-isotope intravenous infusion method could be used to quantify steady-state liver synthesis-secretion of AA from LA under different conditions in rodents and in humans.
authors.affiliation: Brain Physiology and Metabolism Section, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA. gaof@mail.nih.gov
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Dale
authors.initials: D
authors.lastname: Kiesewetter
authors.forename: Lisa
authors.initials: L
authors.lastname: Chang
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
authors.forename: Miki
authors.initials: M
authors.lastname: Igarashi
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000097:blood / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000097:blood / Q000378:metabolism*; D019787:Linoleic Acid / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D043371:Fatty Acids, Omega-6; D016718:Arachidonic Acid; D019787:Linoleic Acid