Eicosapentaenoic and docosahexaenoic acid affect mitochondrial and peroxisomal fatty acid oxidation in relation to substrate preference
Decreased triacylglycerol synthesis within hepatocytes due to decreased diacylglycerol acyltransferase (DGAT) activity has been suggested to be an important mechanism by which diets rich in fish oil lower plasma triacylglycerol levels. New findings suggest that eicosapentaenoic acid (EPA), and not d...
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| Veröffentlicht in: | Lipids 1999-09, Vol.34 (9), p.951-963 |
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| creator | Madsen, L Rustan, A.C Vaagenes, H Berge, K Dyroy, E Berge, R.K |
| description | Decreased triacylglycerol synthesis within hepatocytes due to decreased diacylglycerol acyltransferase (DGAT) activity has been suggested to be an important mechanism by which diets rich in fish oil lower plasma triacylglycerol levels. 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‐lowering 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‐CoA was a poorer substrate than DHA‐CoA for DGAT in isolated rat liver microsomes, and in the presence of EPA, a markedly lower value for the triacyl[3H]glycerol/diacyl[3H]glycerol ratio was observed. The distribution of [1‐14C]palmitic acid was shifted from incorporation into secreted glycerolipids toward oxidation in the presence of EPA (but not DHA) in rat liver parenchymal cells. [1‐14C]EPA was oxidized to a much greater extent than [1‐14C]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‐I 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)‐I activity in both the presence and absence of malonyl‐CoA. Whereas only EPA treatment increased the mRNA levels of CPT‐I, DHA treatment increased the mRNA levels of peroxisomal fatty acyl‐CoA 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. |
| doi_str_mv | 10.1007/s11745-999-0445-x |
| format | Article |
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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‐lowering 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‐CoA was a poorer substrate than DHA‐CoA for DGAT in isolated rat liver microsomes, and in the presence of EPA, a markedly lower value for the triacyl[3H]glycerol/diacyl[3H]glycerol ratio was observed. The distribution of [1‐14C]palmitic acid was shifted from incorporation into secreted glycerolipids toward oxidation in the presence of EPA (but not DHA) in rat liver parenchymal cells. [1‐14C]EPA was oxidized to a much greater extent than [1‐14C]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‐I 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)‐I activity in both the presence and absence of malonyl‐CoA. Whereas only EPA treatment increased the mRNA levels of CPT‐I, DHA treatment increased the mRNA levels of peroxisomal fatty acyl‐CoA 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.</description><identifier>ISSN: 0024-4201</identifier><identifier>EISSN: 1558-9307</identifier><identifier>DOI: 10.1007/s11745-999-0445-x</identifier><identifier>PMID: 10574660</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer‐Verlag</publisher><subject>Acyl-CoA Oxidase ; Acyltransferases - metabolism ; Animals ; blood plasma ; Carbon Radioisotopes ; Carnitine O-Palmitoyltransferase - metabolism ; Carrier Proteins - genetics ; Cells, Cultured ; Diacylglycerol O-Acyltransferase ; Diet ; dietary fat ; Docosahexaenoic Acids - pharmacology ; eicosapentaenoic acid ; Eicosapentaenoic Acid - pharmacology ; Fatty Acid-Binding Protein 7 ; Fatty Acid-Binding Proteins ; Fatty acids ; Fatty Acids - metabolism ; Fish oils ; Glycerol - metabolism ; Glycolipids - metabolism ; hepatocytes ; hypolipidemic effect ; lipid metabolism ; Liver ; Liver - ultrastructure ; Male ; mitochondria ; Mitochondria, Liver - enzymology ; Myelin P2 Protein - genetics ; Neoplasm Proteins ; Nerve Tissue Proteins ; Oleic Acid - pharmacology ; Oxidation ; Oxidation-Reduction ; Oxidoreductases - genetics ; Palmitic Acid - metabolism ; peroxisomes ; Peroxisomes - enzymology ; Plasma ; Rats ; Rats, Wistar ; RNA, Messenger - metabolism ; Rodents ; Substrate Specificity ; Triglycerides - blood ; Tritium</subject><ispartof>Lipids, 1999-09, Vol.34 (9), p.951-963</ispartof><rights>1999 American Oil Chemists' Society (AOCS)</rights><rights>AOCS Press 1999</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4621-4fe2e871b8f088241384a120bd91e7ad8bc213b00f682d843e44604b7b40ac113</citedby><cites>FETCH-LOGICAL-c4621-4fe2e871b8f088241384a120bd91e7ad8bc213b00f682d843e44604b7b40ac113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1007%2Fs11745-999-0445-x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1007%2Fs11745-999-0445-x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10574660$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Madsen, L</creatorcontrib><creatorcontrib>Rustan, A.C</creatorcontrib><creatorcontrib>Vaagenes, H</creatorcontrib><creatorcontrib>Berge, K</creatorcontrib><creatorcontrib>Dyroy, E</creatorcontrib><creatorcontrib>Berge, R.K</creatorcontrib><title>Eicosapentaenoic and docosahexaenoic acid affect mitochondrial and peroxisomal fatty acid oxidation in relation to substrate preference</title><title>Lipids</title><addtitle>Lipids</addtitle><description>Decreased triacylglycerol synthesis within hepatocytes due to decreased diacylglycerol acyltransferase (DGAT) activity has been suggested to be an important mechanism by which diets rich in fish oil lower plasma triacylglycerol levels. 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‐lowering 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‐CoA was a poorer substrate than DHA‐CoA for DGAT in isolated rat liver microsomes, and in the presence of EPA, a markedly lower value for the triacyl[3H]glycerol/diacyl[3H]glycerol ratio was observed. The distribution of [1‐14C]palmitic acid was shifted from incorporation into secreted glycerolipids toward oxidation in the presence of EPA (but not DHA) in rat liver parenchymal cells. [1‐14C]EPA was oxidized to a much greater extent than [1‐14C]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‐I 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)‐I activity in both the presence and absence of malonyl‐CoA. Whereas only EPA treatment increased the mRNA levels of CPT‐I, DHA treatment increased the mRNA levels of peroxisomal fatty acyl‐CoA 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.</description><subject>Acyl-CoA Oxidase</subject><subject>Acyltransferases - metabolism</subject><subject>Animals</subject><subject>blood plasma</subject><subject>Carbon Radioisotopes</subject><subject>Carnitine O-Palmitoyltransferase - metabolism</subject><subject>Carrier Proteins - genetics</subject><subject>Cells, Cultured</subject><subject>Diacylglycerol O-Acyltransferase</subject><subject>Diet</subject><subject>dietary fat</subject><subject>Docosahexaenoic Acids - pharmacology</subject><subject>eicosapentaenoic acid</subject><subject>Eicosapentaenoic Acid - pharmacology</subject><subject>Fatty Acid-Binding Protein 7</subject><subject>Fatty Acid-Binding Proteins</subject><subject>Fatty acids</subject><subject>Fatty Acids - metabolism</subject><subject>Fish oils</subject><subject>Glycerol - metabolism</subject><subject>Glycolipids - metabolism</subject><subject>hepatocytes</subject><subject>hypolipidemic effect</subject><subject>lipid metabolism</subject><subject>Liver</subject><subject>Liver - ultrastructure</subject><subject>Male</subject><subject>mitochondria</subject><subject>Mitochondria, Liver - enzymology</subject><subject>Myelin P2 Protein - genetics</subject><subject>Neoplasm Proteins</subject><subject>Nerve Tissue Proteins</subject><subject>Oleic Acid - pharmacology</subject><subject>Oxidation</subject><subject>Oxidation-Reduction</subject><subject>Oxidoreductases - genetics</subject><subject>Palmitic Acid - metabolism</subject><subject>peroxisomes</subject><subject>Peroxisomes - enzymology</subject><subject>Plasma</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>RNA, Messenger - metabolism</subject><subject>Rodents</subject><subject>Substrate Specificity</subject><subject>Triglycerides - blood</subject><subject>Tritium</subject><issn>0024-4201</issn><issn>1558-9307</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkc1u1TAQhS0EopfCA7CBiAW7gMc_sbNEbYFKVwIJurYcZ0JdJXGwHXHvE_Da-JIiITasPHP0nSOPDiHPgb4BStXbBKCErNu2rakow-EB2YGUum45VQ_JjlImasEonJEnKd2VFUQrH5MzoFKJpqE78vPKu5DsgnO2OAfvKjv3VR9O4i0e_mjO95UdBnS5mnwO7jbMffR2_E0vGMPBpzCVfbA5Hze-aL3NPsyVn6uI4zbnUKW1SznajNUSccCIs8On5NFgx4TP7t9zcvP-6uvFx3r_6cP1xbt97UTDoBYDMtQKOj1QrZkAroUFRru-BVS2151jwDtKh0azXguOQjRUdKoT1DoAfk5eb7lLDN9XTNlMPjkcRztjWJNpWtYKpWQBX_0D3oU1zuVvRmsNXELDCwQb5GJIqRxjlugnG48GqDlVZLaKTKnInCoyh-J5cR-8dhP2fzm2TgqgNuCHH_H4_0Szv_58SVt5Ou7l5hxsMPZb9MncfCn1c8payTmX_Bc0Lail</recordid><startdate>199909</startdate><enddate>199909</enddate><creator>Madsen, L</creator><creator>Rustan, A.C</creator><creator>Vaagenes, H</creator><creator>Berge, K</creator><creator>Dyroy, E</creator><creator>Berge, R.K</creator><general>Springer‐Verlag</general><general>Springer Nature B.V</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>199909</creationdate><title>Eicosapentaenoic and docosahexaenoic acid affect mitochondrial and peroxisomal fatty acid oxidation in relation to substrate preference</title><author>Madsen, L ; Rustan, A.C ; Vaagenes, H ; Berge, K ; Dyroy, E ; Berge, R.K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4621-4fe2e871b8f088241384a120bd91e7ad8bc213b00f682d843e44604b7b40ac113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Acyl-CoA Oxidase</topic><topic>Acyltransferases - 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pharmacology</topic><topic>Oxidation</topic><topic>Oxidation-Reduction</topic><topic>Oxidoreductases - genetics</topic><topic>Palmitic Acid - metabolism</topic><topic>peroxisomes</topic><topic>Peroxisomes - enzymology</topic><topic>Plasma</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>RNA, Messenger - metabolism</topic><topic>Rodents</topic><topic>Substrate Specificity</topic><topic>Triglycerides - blood</topic><topic>Tritium</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Madsen, L</creatorcontrib><creatorcontrib>Rustan, A.C</creatorcontrib><creatorcontrib>Vaagenes, H</creatorcontrib><creatorcontrib>Berge, K</creatorcontrib><creatorcontrib>Dyroy, E</creatorcontrib><creatorcontrib>Berge, R.K</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>Lipids</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Madsen, L</au><au>Rustan, A.C</au><au>Vaagenes, H</au><au>Berge, K</au><au>Dyroy, E</au><au>Berge, R.K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Eicosapentaenoic and docosahexaenoic acid affect mitochondrial and peroxisomal fatty acid oxidation in relation to substrate preference</atitle><jtitle>Lipids</jtitle><addtitle>Lipids</addtitle><date>1999-09</date><risdate>1999</risdate><volume>34</volume><issue>9</issue><spage>951</spage><epage>963</epage><pages>951-963</pages><issn>0024-4201</issn><eissn>1558-9307</eissn><abstract>Decreased triacylglycerol synthesis within hepatocytes due to decreased diacylglycerol acyltransferase (DGAT) activity has been suggested to be an important mechanism by which diets rich in fish oil lower plasma triacylglycerol levels. 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‐lowering 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‐CoA was a poorer substrate than DHA‐CoA for DGAT in isolated rat liver microsomes, and in the presence of EPA, a markedly lower value for the triacyl[3H]glycerol/diacyl[3H]glycerol ratio was observed. The distribution of [1‐14C]palmitic acid was shifted from incorporation into secreted glycerolipids toward oxidation in the presence of EPA (but not DHA) in rat liver parenchymal cells. [1‐14C]EPA was oxidized to a much greater extent than [1‐14C]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‐I 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)‐I activity in both the presence and absence of malonyl‐CoA. Whereas only EPA treatment increased the mRNA levels of CPT‐I, DHA treatment increased the mRNA levels of peroxisomal fatty acyl‐CoA 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.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer‐Verlag</pub><pmid>10574660</pmid><doi>10.1007/s11745-999-0445-x</doi><tpages>13</tpages></addata></record> |
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| ispartof | Lipids, 1999-09, Vol.34 (9), p.951-963 |
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| subjects | Acyl-CoA Oxidase Acyltransferases - metabolism Animals blood plasma Carbon Radioisotopes Carnitine O-Palmitoyltransferase - metabolism Carrier Proteins - genetics Cells, Cultured Diacylglycerol O-Acyltransferase Diet dietary fat Docosahexaenoic Acids - pharmacology eicosapentaenoic acid Eicosapentaenoic Acid - pharmacology Fatty Acid-Binding Protein 7 Fatty Acid-Binding Proteins Fatty acids Fatty Acids - metabolism Fish oils Glycerol - metabolism Glycolipids - metabolism hepatocytes hypolipidemic effect lipid metabolism Liver Liver - ultrastructure Male mitochondria Mitochondria, Liver - enzymology Myelin P2 Protein - genetics Neoplasm Proteins Nerve Tissue Proteins Oleic Acid - pharmacology Oxidation Oxidation-Reduction Oxidoreductases - genetics Palmitic Acid - metabolism peroxisomes Peroxisomes - enzymology Plasma Rats Rats, Wistar RNA, Messenger - metabolism Rodents Substrate Specificity Triglycerides - blood Tritium |
| title | Eicosapentaenoic and docosahexaenoic acid affect mitochondrial and peroxisomal fatty acid oxidation in relation to substrate preference |
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