title: Elaidate, an 18-carbon trans-monoenoic fatty acid, inhibits β-oxidation in human peripheral blood macrophages.
abstract: Consumption of trans-unsaturated fatty acids promotes atherosclerosis, but whether degradation of fats in macrophages is altered by trans-unsaturated fatty acids is unknown. We compared the metabolism of oleate (C18:1Δ9-10 cis; (Z)-octadec-9-enoate), elaidate (C18:Δ9-10 trans; (E)-octadec-9-enoate), and stearate (C18:0, octadecanoate) in adherent peripheral human macrophages. Metabolism was followed by measurement of acylcarnitines in cell supernatants by MS/MS, determination of cellular fatty acid content by GC/MS, and assessment of β-oxidation rates using radiolabeled fatty acids. Cells incubated for 44 h in 100 µM elaidate accumulated more unsaturated fatty acids, including both longer- and shorter-chain, and had reduced C18:0 relative to those incubated with oleate or stearate. Both C12:1 and C18:1 acylcarnitines accumulated in supernatants of macrophages exposed to trans fats. These results suggested β-oxidation inhibition one reaction proximal to the trans bond. Comparison of [1-(14)C]oleate to [1-(14)C]elaidate catabolism showed that elaidate completed the first round of fatty acid β-oxidation at rates comparable to oleate. Yet, in competitive β-oxidation assays with [9,10-(3)H]oleate, tritium release rate decreased when unlabeled oleate was replaced by the same quantity of elaidate. These data show specific inhibition of monoenoic fat catabolism by elaidate that is not shared by other atherogenic fats.
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, 15261.
authors.forename: Janelle R
authors.initials: JR
authors.lastname: Zacherl
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Mihalik
authors.forename: Donald H
authors.initials: DH
authors.lastname: Chace
authors.forename: Tyson C
authors.initials: TC
authors.lastname: Christensen
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Robinson
authors.forename: Harry C
authors.initials: HC
authors.lastname: Blair
mesh_terms: D002331:Carnitine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D005227:Fatty Acids / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009829:Oleic Acids; D010084:Oxidation-Reduction / Q000187:drug effects; D010938:Plant Oils / Q000494:pharmacology; D013228:Stearates / Q000378:metabolism / Q000494:pharmacology; D053719:Tandem Mass Spectrometry
chemical_list: D005227:Fatty Acids; D009829:Oleic Acids; D010938:Plant Oils; D013228:Stearates; C116917:acylcarnitine; D019301:Oleic Acid; C011459:elaidic acid; D002331:Carnitine
keywords: ACYLCARNITINE; ELAIDIC ACID; ENOYL-CoA δ-ISOMERASE; FATTY ACID β-OXIDATION; MACROPHAGE; trans-FATTY ACIDS