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New findings suggest that eicosapentaenoic acid (EPA), and not docosahexaenoic acid (DHA), lowers plasma triacylglycerol by increased mitochondrial fatty acid oxidation and decreased availability of fatty acids for triacylglycerol synthesis. To contribute to the understanding of the triacylglycerol\u2010lowering mechanism of fish oil, the different metabolic properties of EPA and DHA were studied in rat liver parenchymal cells and isolated rat liver organelles. EPA\u2010CoA was a poorer substrate than DHA\u2010CoA for DGAT in isolated rat liver microsomes, and in the presence of EPA, a markedly lower value for the triacyl[<jats:sup>3<\/jats:sup>H]glycerol\/diacyl[<jats:sup>3<\/jats:sup>H]glycerol ratio was observed. The distribution of [1\u2010<jats:sup>14<\/jats:sup>C]palmitic acid was shifted from incorporation into secreted glycerolipids toward oxidation in the presence of EPA (but not DHA) in rat liver parenchymal cells. [1\u2010<jats:sup>14<\/jats:sup>C]EPA was oxidized to a much greater extent than [1\u2010<jats:sup>14<\/jats:sup>C]DHA in rat liver parenchymal cells, isolated peroxisomes, and especially in purified mitochondria. As the oxidation of EPA was more effective and sensitive to the CPT\u2010I inhibitor, etomoxir, when measured in a combination of both mitochondria and peroxisomes, we hypothesized that both are involved in EPA oxidation, whereas DHA mainly is oxidized in peroxisomes. In rats, EPA treatment lowered plasma triacylglycerol and increased hepatic mitochondrial fatty acid oxidation and carnitine palmitoyltransferase (CPT)\u2010I activity in both the presence and absence of malonyl\u2010CoA. Whereas only EPA treatment increased the mRNA levels of CPT\u2010I, DHA treatment increased the mRNA levels of peroxisomal fatty acyl\u2010CoA oxidase and fatty acid binding protein more effectively than EPA treatment. In conclusion, EPA and DHA affect cellular organelles in relation to their substrate preference. The present study strongly supports the hypothesis that EPA, and not DHA, lowers plasma triacylglycerol by increased mitochondrial fatty acid oxidation.<\/jats:p>","DOI":"10.1007\/s11745-999-0445-x","type":"journal-article","created":{"date-parts":[[2006,11,13]],"date-time":"2006-11-13T13:48:53Z","timestamp":1163425733000},"page":"951-963","source":"Crossref","is-referenced-by-count":150,"title":["Eicosapentaenoic and docosahexaenoic acid affect mitochondrial and peroxisomal fatty acid oxidation in relation to substrate preference"],"prefix":"10.1002","volume":"34","author":[{"given":"Lise","family":"Madsen","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry University of Bergen, Haukeland Hospital Bergen N\u20105021 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arild C.","family":"Rustan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hege","family":"Vaagenes","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry University of Bergen, Haukeland Hospital Bergen N\u20105021 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjetil","family":"Berge","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry University of Bergen, Haukeland Hospital Bergen N\u20105021 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Endre","family":"Dyr\u00f8y","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry University of Bergen, Haukeland Hospital Bergen N\u20105021 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf K.","family":"Berge","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry University of Bergen, Haukeland Hospital Bergen N\u20105021 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[1999,9]]},"reference":[{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/65.5.1645S"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/66.4.1020S"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(84)90209-1"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(86)90266-3"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)38418-2"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2830333"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1993.tb35705.x"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)37255-2"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/66.2.254"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02537204"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(92)90291-3"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02535987"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02537089"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02523828"},{"key":"e_1_2_2_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)37159-5"},{"key":"e_1_2_2_17_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2680001"},{"key":"e_1_2_2_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst0210487"},{"key":"e_1_2_2_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/273011a0"},{"key":"e_1_2_2_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.16.10.1229"},{"key":"e_1_2_2_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(92)90187-Z"},{"key":"e_1_2_2_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)36944-3"},{"key":"e_1_2_2_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02536084"},{"key":"e_1_2_2_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02637050"},{"key":"e_1_2_2_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)41315-X"},{"key":"e_1_2_2_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02522617"},{"key":"e_1_2_2_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)33296-X"},{"key":"e_1_2_2_28_1","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1093\/jn\/126.11.2784","article-title":"Docosahexaenoic Acid\u2010Rich Fish Oil Does Not Affect Serum Lipid Concentrations of Normolipidemic Young Adults","volume":"126","author":"Hamazaki T.","year":"1996","journal-title":"J. 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