title: Whole-body synthesis-secretion rates of long-chain n-3 PUFAs from circulating unesterified alpha-linolenic acid in unanesthetized rats.
abstract: Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), long-chain n-3 PUFAs important for brain and heart function, can be obtained from dietary fish products or by liver synthesis from alpha-linolenic acid (alpha-LNA). Their daily human dietary requirements are not clear, and their liver synthesis rates in humans and nonhumans are unknown. We estimated whole-body (presumably liver) synthesis rates in unanesthetized rats by infusing [U-(13)C]alpha-LNA intravenously for 2 h and measuring labeled and unlabeled n-3 PUFA in arterial plasma using negative chemical ionization GC-MS. Newly synthesized esterified [(13)C]DHA, [(13)C]EPA, and [(13)C]docosapentaenoic acid (DPA) appeared in arterial plasma after 60 min of infusion, then their concentrations rose in an S-shaped manner. Esterified concentration x plasma volume data were fit with a sigmoidal equation, whose peak first derivatives provided synthesis rates of unlabeled EPA, DPA, and DHA equal to 8.40, 6.27, and 9.84 mumol/day, respectively. The DHA synthesis rate exceeded the published daily rat brain DHA consumption rate by 30-fold, suggesting that liver synthesis from alpha-LNA could maintain brain DHA homeostasis were DHA absent from the diet. This stable isotope infusion method could be used to quantify whole-body DHA synthesis rates in human subjects.
authors.affiliation: Brain Physiology and Metabolism Section, National Institute on Aging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, 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: Kaizong
authors.initials: K
authors.lastname: Ma
authors.forename: Jane M
authors.initials: JM
authors.lastname: Bell
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
authors.forename: Miki
authors.initials: M
authors.lastname: Igarashi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002247:Carbon Isotopes; D004281:Docosahexaenoic Acids / Q000097:blood / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000096:biosynthesis / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000096:biosynthesis* / Q000097:blood; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D017962:alpha-Linolenic Acid / Q000097:blood*
chemical_list: D002247:Carbon Isotopes; D015525:Fatty Acids, Omega-3; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid