Omega 3 Improves Both apoB100-containing Lipoprotein Turnover and their Sphingolipid Profile in Hypertriglyceridemia

Abstract Context Evidence for an association between sphingolipids and metabolic disorders is increasingly reported. Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) improve apolipoprotein B100 (apoB100)-containing lipoprotein metabolism, but their effects on the sphingolipid content in...

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Veröffentlicht in:The journal of clinical endocrinology and metabolism 2020-10, Vol.105 (10), p.3152-3164
Hauptverfasser: Ferchaud-Roucher, Véronique, Zair, Yassine, Aguesse, Audrey, Krempf, Michel, Ouguerram, Khadija
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container_issue 10
container_start_page 3152
container_title The journal of clinical endocrinology and metabolism
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creator Ferchaud-Roucher, Véronique
Zair, Yassine
Aguesse, Audrey
Krempf, Michel
Ouguerram, Khadija
description Abstract Context Evidence for an association between sphingolipids and metabolic disorders is increasingly reported. Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) improve apolipoprotein B100 (apoB100)-containing lipoprotein metabolism, but their effects on the sphingolipid content in lipoproteins remain unknown. Objectives In subjects with hypertriglyceridemia, we analyzed the effect of n-3 LC-PUFAs on the turnover apoB100-containing lipoproteins and on their sphingolipid content and looked for the possible association between these lipid levels and apoB100-containing lipoprotein turnover parameters. Methods Six subjects underwent a kinetic study before and after n-3 supplementation for 2 months with 1 g of fish oil 3 times day containing 360 mg of eicosapentaenoic acid (EPA) and 240 mg of docosahexaenoic acid (DHA) in the form of triglycerides. We examined apoB100-containing lipoprotein turnover by primed perfusion labeled [5,5,5-2H3]-leucine and determined kinetic parameters using a multicompartmental model. We quantified sphingolipid species content in lipoproteins using mass spectrometry. Results Supplementation decreased very low-density lipoprotein (VLDL), triglyceride, and apoB100 concentrations. The VLDL neutral and polar lipids showed increased n-3 LC-PUFA and decreased n-6 LC-PUFA content. The conversion rate of VLDL1 to VLDL2 and of VLDL2 to LDL was increased. We measured a decrease in total apoB100 production and VLDL1 production. Supplementation reduced the total ceramide concentration in VLDL while the sphingomyelin content in LDL was increased. We found positive correlations between plasma palmitic acid and VLDL ceramide and between VLDL triglyceride and VLDL ceramide, and inverse correlations between VLDL n-3 LC-PUFA and VLDL production. Conclusion Based on these results, we hypothesize that the improvement in apoB100 metabolism during n-3 LC-PUFA supplementation is contributed to by changes in sphingolipids
doi_str_mv 10.1210/clinem/dgaa459
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Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) improve apolipoprotein B100 (apoB100)-containing lipoprotein metabolism, but their effects on the sphingolipid content in lipoproteins remain unknown. Objectives In subjects with hypertriglyceridemia, we analyzed the effect of n-3 LC-PUFAs on the turnover apoB100-containing lipoproteins and on their sphingolipid content and looked for the possible association between these lipid levels and apoB100-containing lipoprotein turnover parameters. Methods Six subjects underwent a kinetic study before and after n-3 supplementation for 2 months with 1 g of fish oil 3 times day containing 360 mg of eicosapentaenoic acid (EPA) and 240 mg of docosahexaenoic acid (DHA) in the form of triglycerides. We examined apoB100-containing lipoprotein turnover by primed perfusion labeled [5,5,5-2H3]-leucine and determined kinetic parameters using a multicompartmental model. We quantified sphingolipid species content in lipoproteins using mass spectrometry. Results Supplementation decreased very low-density lipoprotein (VLDL), triglyceride, and apoB100 concentrations. The VLDL neutral and polar lipids showed increased n-3 LC-PUFA and decreased n-6 LC-PUFA content. The conversion rate of VLDL1 to VLDL2 and of VLDL2 to LDL was increased. We measured a decrease in total apoB100 production and VLDL1 production. Supplementation reduced the total ceramide concentration in VLDL while the sphingomyelin content in LDL was increased. We found positive correlations between plasma palmitic acid and VLDL ceramide and between VLDL triglyceride and VLDL ceramide, and inverse correlations between VLDL n-3 LC-PUFA and VLDL production. Conclusion Based on these results, we hypothesize that the improvement in apoB100 metabolism during n-3 LC-PUFA supplementation is contributed to by changes in sphingolipids</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/clinem/dgaa459</identifier><identifier>PMID: 32805740</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Adult ; Apolipoprotein B-100 - metabolism ; Apolipoproteins ; Care and treatment ; Ceramide ; Development and progression ; Dietary Supplements ; Docosahexaenoic acid ; Eicosapentaenoic acid ; Fatty Acids, Omega-3 - administration &amp; dosage ; Fish oils ; Health aspects ; Humanities and Social Sciences ; Humans ; Hyperlipidemia ; Hypertriglyceridemia ; Hypertriglyceridemia - blood ; Hypertriglyceridemia - drug therapy ; Hypertriglyceridemia - metabolism ; Leucine ; Lipid metabolism ; Lipids ; Lipoproteins ; Lipoproteins (very low density) ; Lipoproteins, VLDL - blood ; Lipoproteins, VLDL - metabolism ; Low density lipoprotein ; Male ; Mass spectroscopy ; Metabolic disorders ; Metabolism ; Middle Aged ; Omega-3 fatty acids ; Palmitic acid ; Perfusion ; Physiological aspects ; Pilot Projects ; Polyunsaturated fatty acids ; Sphingolipids ; Sphingolipids - blood ; Sphingolipids - metabolism ; Sphingomyelin ; Supplements ; Treatment Outcome ; Triglycerides</subject><ispartof>The journal of clinical endocrinology and metabolism, 2020-10, Vol.105 (10), p.3152-3164</ispartof><rights>Published by Oxford University Press on behalf of the Endocrine Society 2020 2020</rights><rights>Copyright © Oxford University Press 2015</rights><rights>Published by Oxford University Press on behalf of the Endocrine Society 2020.</rights><rights>COPYRIGHT 2020 Oxford University Press</rights><rights>Published by Oxford University Press on behalf of the Endocrine Society 2020</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5435-1383b5fb1ba9bc23418c4aeeebd141b4cfe03fcdb8db9b41a9ccf645f8248d633</citedby><cites>FETCH-LOGICAL-c5435-1383b5fb1ba9bc23418c4aeeebd141b4cfe03fcdb8db9b41a9ccf645f8248d633</cites><orcidid>0000-0003-0058-6462 ; 0000-0001-6809-1488</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2471030741?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,780,784,885,21388,21389,27924,27925,33530,33531,33744,33745,43659,43805,64385,64387,64389,72469,73123,73128,73129,73131</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32805740$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.inrae.fr/hal-03207838$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Ferchaud-Roucher, Véronique</creatorcontrib><creatorcontrib>Zair, Yassine</creatorcontrib><creatorcontrib>Aguesse, Audrey</creatorcontrib><creatorcontrib>Krempf, Michel</creatorcontrib><creatorcontrib>Ouguerram, Khadija</creatorcontrib><title>Omega 3 Improves Both apoB100-containing Lipoprotein Turnover and their Sphingolipid Profile in Hypertriglyceridemia</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Abstract Context Evidence for an association between sphingolipids and metabolic disorders is increasingly reported. Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) improve apolipoprotein B100 (apoB100)-containing lipoprotein metabolism, but their effects on the sphingolipid content in lipoproteins remain unknown. Objectives In subjects with hypertriglyceridemia, we analyzed the effect of n-3 LC-PUFAs on the turnover apoB100-containing lipoproteins and on their sphingolipid content and looked for the possible association between these lipid levels and apoB100-containing lipoprotein turnover parameters. Methods Six subjects underwent a kinetic study before and after n-3 supplementation for 2 months with 1 g of fish oil 3 times day containing 360 mg of eicosapentaenoic acid (EPA) and 240 mg of docosahexaenoic acid (DHA) in the form of triglycerides. We examined apoB100-containing lipoprotein turnover by primed perfusion labeled [5,5,5-2H3]-leucine and determined kinetic parameters using a multicompartmental model. We quantified sphingolipid species content in lipoproteins using mass spectrometry. Results Supplementation decreased very low-density lipoprotein (VLDL), triglyceride, and apoB100 concentrations. The VLDL neutral and polar lipids showed increased n-3 LC-PUFA and decreased n-6 LC-PUFA content. The conversion rate of VLDL1 to VLDL2 and of VLDL2 to LDL was increased. We measured a decrease in total apoB100 production and VLDL1 production. Supplementation reduced the total ceramide concentration in VLDL while the sphingomyelin content in LDL was increased. We found positive correlations between plasma palmitic acid and VLDL ceramide and between VLDL triglyceride and VLDL ceramide, and inverse correlations between VLDL n-3 LC-PUFA and VLDL production. Conclusion Based on these results, we hypothesize that the improvement in apoB100 metabolism during n-3 LC-PUFA supplementation is contributed to by changes in sphingolipids</description><subject>Adult</subject><subject>Apolipoprotein B-100 - metabolism</subject><subject>Apolipoproteins</subject><subject>Care and treatment</subject><subject>Ceramide</subject><subject>Development and progression</subject><subject>Dietary Supplements</subject><subject>Docosahexaenoic acid</subject><subject>Eicosapentaenoic acid</subject><subject>Fatty Acids, Omega-3 - administration &amp; dosage</subject><subject>Fish oils</subject><subject>Health aspects</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Hyperlipidemia</subject><subject>Hypertriglyceridemia</subject><subject>Hypertriglyceridemia - blood</subject><subject>Hypertriglyceridemia - drug therapy</subject><subject>Hypertriglyceridemia - metabolism</subject><subject>Leucine</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Lipoproteins</subject><subject>Lipoproteins (very low density)</subject><subject>Lipoproteins, VLDL - blood</subject><subject>Lipoproteins, VLDL - metabolism</subject><subject>Low density lipoprotein</subject><subject>Male</subject><subject>Mass spectroscopy</subject><subject>Metabolic disorders</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Omega-3 fatty acids</subject><subject>Palmitic acid</subject><subject>Perfusion</subject><subject>Physiological aspects</subject><subject>Pilot Projects</subject><subject>Polyunsaturated fatty acids</subject><subject>Sphingolipids</subject><subject>Sphingolipids - blood</subject><subject>Sphingolipids - metabolism</subject><subject>Sphingomyelin</subject><subject>Supplements</subject><subject>Treatment Outcome</subject><subject>Triglycerides</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkkFr3DAQhUVpabZprz0WQS_pwYlGktf2cRPabmAhhabQm5Dlsa1UtlzZTth_X5ndJlAClRBC4pvHzOMR8h7YOXBgF8bZHruLqtFapsULsoJCpkkGRfaSrBjjkBQZ_3lC3ozjHWMgZSpekxPBc5Zmkq3IdNNho6mg190Q_D2O9NJPLdWDvwTGEuP7Sdve9g3d2cFHZELb09s59BEOVPcVnVq0gX4f2kh5Zwdb0W_B19Yhjeh2P2CYgm3c3mCwFXZWvyWvau1GfHe8T8mPL59vr7bJ7ubr9dVml5hUijQBkYsyrUsodVEaLiTkRmpELCuQUEpTIxO1qcq8KotSgi6MqdcyrXMu82otxCn5dNBttVNDsJ0Oe-W1VdvNTi1_THCW5SK_h8ieHdg44-8Zx0l1djTonO7Rz6PisSMouJRZRD_-g975aEicJFIZMMEyCU9Uox0q29d-CtosomqzjmICWL5onT9Dxb0YFd3HxcdnC0zw4xiwfhwMmFoioQ6RUMdIxIIPx27nssPqEf-bgQjIA_Dg3YRh_OXmBwyqRe2mVrG45DrLE844g-WVxAPpk7l-Hv7Xwx_03NCH</recordid><startdate>202010</startdate><enddate>202010</enddate><creator>Ferchaud-Roucher, Véronique</creator><creator>Zair, Yassine</creator><creator>Aguesse, Audrey</creator><creator>Krempf, Michel</creator><creator>Ouguerram, Khadija</creator><general>Oxford University Press</general><general>Copyright Oxford University Press</general><general>Endocrine Society</general><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>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>1XC</scope><scope>BXJBU</scope><orcidid>https://orcid.org/0000-0003-0058-6462</orcidid><orcidid>https://orcid.org/0000-0001-6809-1488</orcidid></search><sort><creationdate>202010</creationdate><title>Omega 3 Improves Both apoB100-containing Lipoprotein Turnover and their Sphingolipid Profile in Hypertriglyceridemia</title><author>Ferchaud-Roucher, Véronique ; Zair, Yassine ; Aguesse, Audrey ; Krempf, Michel ; Ouguerram, Khadija</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5435-1383b5fb1ba9bc23418c4aeeebd141b4cfe03fcdb8db9b41a9ccf645f8248d633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Apolipoprotein B-100 - metabolism</topic><topic>Apolipoproteins</topic><topic>Care and treatment</topic><topic>Ceramide</topic><topic>Development and progression</topic><topic>Dietary Supplements</topic><topic>Docosahexaenoic acid</topic><topic>Eicosapentaenoic acid</topic><topic>Fatty Acids, Omega-3 - administration &amp; dosage</topic><topic>Fish oils</topic><topic>Health aspects</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Hyperlipidemia</topic><topic>Hypertriglyceridemia</topic><topic>Hypertriglyceridemia - blood</topic><topic>Hypertriglyceridemia - drug therapy</topic><topic>Hypertriglyceridemia - metabolism</topic><topic>Leucine</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>Lipoproteins</topic><topic>Lipoproteins (very low density)</topic><topic>Lipoproteins, VLDL - blood</topic><topic>Lipoproteins, VLDL - metabolism</topic><topic>Low density lipoprotein</topic><topic>Male</topic><topic>Mass spectroscopy</topic><topic>Metabolic disorders</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Omega-3 fatty acids</topic><topic>Palmitic acid</topic><topic>Perfusion</topic><topic>Physiological aspects</topic><topic>Pilot Projects</topic><topic>Polyunsaturated fatty acids</topic><topic>Sphingolipids</topic><topic>Sphingolipids - blood</topic><topic>Sphingolipids - metabolism</topic><topic>Sphingomyelin</topic><topic>Supplements</topic><topic>Treatment Outcome</topic><topic>Triglycerides</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ferchaud-Roucher, Véronique</creatorcontrib><creatorcontrib>Zair, Yassine</creatorcontrib><creatorcontrib>Aguesse, Audrey</creatorcontrib><creatorcontrib>Krempf, Michel</creatorcontrib><creatorcontrib>Ouguerram, Khadija</creatorcontrib><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>Calcium &amp; 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Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) improve apolipoprotein B100 (apoB100)-containing lipoprotein metabolism, but their effects on the sphingolipid content in lipoproteins remain unknown. Objectives In subjects with hypertriglyceridemia, we analyzed the effect of n-3 LC-PUFAs on the turnover apoB100-containing lipoproteins and on their sphingolipid content and looked for the possible association between these lipid levels and apoB100-containing lipoprotein turnover parameters. Methods Six subjects underwent a kinetic study before and after n-3 supplementation for 2 months with 1 g of fish oil 3 times day containing 360 mg of eicosapentaenoic acid (EPA) and 240 mg of docosahexaenoic acid (DHA) in the form of triglycerides. We examined apoB100-containing lipoprotein turnover by primed perfusion labeled [5,5,5-2H3]-leucine and determined kinetic parameters using a multicompartmental model. We quantified sphingolipid species content in lipoproteins using mass spectrometry. Results Supplementation decreased very low-density lipoprotein (VLDL), triglyceride, and apoB100 concentrations. The VLDL neutral and polar lipids showed increased n-3 LC-PUFA and decreased n-6 LC-PUFA content. The conversion rate of VLDL1 to VLDL2 and of VLDL2 to LDL was increased. We measured a decrease in total apoB100 production and VLDL1 production. Supplementation reduced the total ceramide concentration in VLDL while the sphingomyelin content in LDL was increased. We found positive correlations between plasma palmitic acid and VLDL ceramide and between VLDL triglyceride and VLDL ceramide, and inverse correlations between VLDL n-3 LC-PUFA and VLDL production. Conclusion Based on these results, we hypothesize that the improvement in apoB100 metabolism during n-3 LC-PUFA supplementation is contributed to by changes in sphingolipids</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>32805740</pmid><doi>10.1210/clinem/dgaa459</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-0058-6462</orcidid><orcidid>https://orcid.org/0000-0001-6809-1488</orcidid><oa>free_for_read</oa></addata></record>
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1945-7197
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subjects Adult
Apolipoprotein B-100 - metabolism
Apolipoproteins
Care and treatment
Ceramide
Development and progression
Dietary Supplements
Docosahexaenoic acid
Eicosapentaenoic acid
Fatty Acids, Omega-3 - administration & dosage
Fish oils
Health aspects
Humanities and Social Sciences
Humans
Hyperlipidemia
Hypertriglyceridemia
Hypertriglyceridemia - blood
Hypertriglyceridemia - drug therapy
Hypertriglyceridemia - metabolism
Leucine
Lipid metabolism
Lipids
Lipoproteins
Lipoproteins (very low density)
Lipoproteins, VLDL - blood
Lipoproteins, VLDL - metabolism
Low density lipoprotein
Male
Mass spectroscopy
Metabolic disorders
Metabolism
Middle Aged
Omega-3 fatty acids
Palmitic acid
Perfusion
Physiological aspects
Pilot Projects
Polyunsaturated fatty acids
Sphingolipids
Sphingolipids - blood
Sphingolipids - metabolism
Sphingomyelin
Supplements
Treatment Outcome
Triglycerides
title Omega 3 Improves Both apoB100-containing Lipoprotein Turnover and their Sphingolipid Profile in Hypertriglyceridemia
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