title: Aging decreases rate of docosahexaenoic acid synthesis-secretion from circulating unesterified α-linolenic acid by rat liver.
abstract: Docosahexaenoic acid (DHA, 22:6n-3), an n-3 polyunsaturated fatty acid (PUFA) found at high concentrations in brain and retina and critical to their function, can be obtained from fish products or be synthesized from circulating α-linolenic acid (α-LNA, 18:3n-3) mainly in the liver. With aging, liver synthetic enzymes are reported reduced or unchanged in the rat. To test whether liver synthesis-secretion of DHA from α-LNA changes with age, we measured whole-body DHA conversion coefficients and rates in unanesthetized adult male Fischer-344 rats aged 10, 20, or 30 months, fed an eicosapentaenoic acid (EPA, 20:5n-3)- and DHA-containing diet. Unesterified [U- (13) C]α-LNA bound to albumin was infused intravenously for 2 h, while [(13) C]-esterified n-3 PUFAs were measured in arterial plasma, as were unlabeled unesterified and esterified PUFA concentrations. Plasma unesterified n-3 PUFA concentrations declined with age, but esterified n-3 PUFA concentrations did not change significantly. Calculated conversion coefficients were not changed significantly with age, whereas synthesis-secretion rates (product of conversion coefficient and unesterified plasma α-LNA concentration) of esterified DHA and n-3 DPA were reduced. Turnovers of esterified n-3 PUFAs in plasma decreased with age, whereas half-lives increased. The results suggest that hepatic capacity to synthesize DHA and other n-3 PUFAs from circulating α-LNA is maintained with age in the rat, but that reduced plasma α-LNA availability reduces net synthesis-secretion. As unesterified plasma DHA is the form that is incorporated preferentially into brain phospholipid, its reduced synthesis may be deleterious to brain function in aged rats.
authors.affiliation: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. fgao1@partners.org
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Ameer Y
authors.initials: AY
authors.lastname: Taha
authors.forename: Kaizong
authors.initials: K
authors.lastname: Ma
authors.forename: Lisa
authors.initials: L
authors.lastname: Chang
authors.forename: Dale
authors.initials: D
authors.lastname: Kiesewetter
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D004281:Docosahexaenoic Acids / Q000096:biosynthesis* / Q000378:metabolism*; D005500:Follow-Up Studies; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D017962:alpha-Linolenic Acid / Q000097:blood*
chemical_list: D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids