Binding of polyunsaturated fatty acids to LXRα and modulation of SREBP-1 interaction with a specific SCD1 promoter element
Stearoyl‐CoA desaturase 1 (SCD1) is the rate limiting enzyme in unsaturated fatty acid biosynthesis. This enzyme has an important role in the regulation of hepatic lipogenesis and lipid oxidation, and alterations in these pathways may lead to several diseases. We examined, in HepG2 cell cultures, th...
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| Veröffentlicht in: | Cell biochemistry and function 2014-12, Vol.32 (8), p.637-646 |
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| creator | Caputo, Mariella De Rosa, Maria Caterina Rescigno, Tania Zirpoli, Hylde Vassallo, Antonio De Tommasi, Nunziatina Torino, Gaetano Tecce, Mario Felice |
| description | Stearoyl‐CoA desaturase 1 (SCD1) is the rate limiting enzyme in unsaturated fatty acid biosynthesis. This enzyme has an important role in the regulation of hepatic lipogenesis and lipid oxidation, and alterations in these pathways may lead to several diseases. We examined, in HepG2 cell cultures, the mechanism of SCD1 regulation considering the involvement of two transcription factors: liver X receptor alpha (LXRα) and sterol regulatory element‐binding protein‐1 (SREBP‐1), also investigating the effect of dietary polyunsaturated fatty acids (PUFAs) on this process. The analysis of SCD1 promoter allowed to identify a functional SREBP‐1 binding site (SRE 1). LXRα activation increased SCD1 protein level through upregulation of SREBP‐1 and its consequent binding to SRE 1 sequence. Polyunsaturated docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) and arachidonic acid (AA, C20:4) were able to reduce SREBP‐1 binding to SCD1 promoter, while saturated stearic acid (SA, C18:0) did not give any effect. Surface plasmon resonance analysis showed a direct binding of DHA, EPA and AA to LXRα. These data indicate a direct inhibitory interaction of PUFAs with LXRα, a consequent reduction of SREBP‐1 and of its binding to SCD1 promoter. This information provides a mechanism to explain the regulation of lipogenic pathways induced by PUFAs. Copyright © 2014 John Wiley & Sons, Ltd. |
| doi_str_mv | 10.1002/cbf.3067 |
| format | Article |
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This enzyme has an important role in the regulation of hepatic lipogenesis and lipid oxidation, and alterations in these pathways may lead to several diseases. We examined, in HepG2 cell cultures, the mechanism of SCD1 regulation considering the involvement of two transcription factors: liver X receptor alpha (LXRα) and sterol regulatory element‐binding protein‐1 (SREBP‐1), also investigating the effect of dietary polyunsaturated fatty acids (PUFAs) on this process. The analysis of SCD1 promoter allowed to identify a functional SREBP‐1 binding site (SRE 1). LXRα activation increased SCD1 protein level through upregulation of SREBP‐1 and its consequent binding to SRE 1 sequence. Polyunsaturated docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) and arachidonic acid (AA, C20:4) were able to reduce SREBP‐1 binding to SCD1 promoter, while saturated stearic acid (SA, C18:0) did not give any effect. Surface plasmon resonance analysis showed a direct binding of DHA, EPA and AA to LXRα. These data indicate a direct inhibitory interaction of PUFAs with LXRα, a consequent reduction of SREBP‐1 and of its binding to SCD1 promoter. This information provides a mechanism to explain the regulation of lipogenic pathways induced by PUFAs. Copyright © 2014 John Wiley & Sons, Ltd.</description><identifier>ISSN: 0263-6484</identifier><identifier>EISSN: 1099-0844</identifier><identifier>DOI: 10.1002/cbf.3067</identifier><identifier>PMID: 25264165</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>arachidonic acid ; docosahexaenoic acid ; eicosapentaenoic acid ; Fatty Acids, Unsaturated - metabolism ; gene expression ; Hep G2 Cells ; Humans ; lipogenic pathways ; Liver X Receptors ; Orphan Nuclear Receptors - metabolism ; Protein Binding ; Response Elements ; Stearoyl-CoA Desaturase - genetics ; Stearoyl-CoA Desaturase - metabolism ; Sterol Regulatory Element Binding Protein 1 - genetics ; Sterol Regulatory Element Binding Protein 1 - metabolism ; surface plasmon resonance</subject><ispartof>Cell biochemistry and function, 2014-12, Vol.32 (8), p.637-646</ispartof><rights>Copyright © 2014 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3597-7cb5e05a74097496ebdbaa9777a6634a9a57841a3b4d36e07936bad02ad67d513</citedby><cites>FETCH-LOGICAL-c3597-7cb5e05a74097496ebdbaa9777a6634a9a57841a3b4d36e07936bad02ad67d513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcbf.3067$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcbf.3067$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25264165$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Caputo, Mariella</creatorcontrib><creatorcontrib>De Rosa, Maria Caterina</creatorcontrib><creatorcontrib>Rescigno, Tania</creatorcontrib><creatorcontrib>Zirpoli, Hylde</creatorcontrib><creatorcontrib>Vassallo, Antonio</creatorcontrib><creatorcontrib>De Tommasi, Nunziatina</creatorcontrib><creatorcontrib>Torino, Gaetano</creatorcontrib><creatorcontrib>Tecce, Mario Felice</creatorcontrib><title>Binding of polyunsaturated fatty acids to LXRα and modulation of SREBP-1 interaction with a specific SCD1 promoter element</title><title>Cell biochemistry and function</title><addtitle>Cell Biochem Funct</addtitle><description>Stearoyl‐CoA desaturase 1 (SCD1) is the rate limiting enzyme in unsaturated fatty acid biosynthesis. This enzyme has an important role in the regulation of hepatic lipogenesis and lipid oxidation, and alterations in these pathways may lead to several diseases. We examined, in HepG2 cell cultures, the mechanism of SCD1 regulation considering the involvement of two transcription factors: liver X receptor alpha (LXRα) and sterol regulatory element‐binding protein‐1 (SREBP‐1), also investigating the effect of dietary polyunsaturated fatty acids (PUFAs) on this process. The analysis of SCD1 promoter allowed to identify a functional SREBP‐1 binding site (SRE 1). LXRα activation increased SCD1 protein level through upregulation of SREBP‐1 and its consequent binding to SRE 1 sequence. Polyunsaturated docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) and arachidonic acid (AA, C20:4) were able to reduce SREBP‐1 binding to SCD1 promoter, while saturated stearic acid (SA, C18:0) did not give any effect. Surface plasmon resonance analysis showed a direct binding of DHA, EPA and AA to LXRα. These data indicate a direct inhibitory interaction of PUFAs with LXRα, a consequent reduction of SREBP‐1 and of its binding to SCD1 promoter. This information provides a mechanism to explain the regulation of lipogenic pathways induced by PUFAs. Copyright © 2014 John Wiley & Sons, Ltd.</description><subject>arachidonic acid</subject><subject>docosahexaenoic acid</subject><subject>eicosapentaenoic acid</subject><subject>Fatty Acids, Unsaturated - metabolism</subject><subject>gene expression</subject><subject>Hep G2 Cells</subject><subject>Humans</subject><subject>lipogenic pathways</subject><subject>Liver X Receptors</subject><subject>Orphan Nuclear Receptors - metabolism</subject><subject>Protein Binding</subject><subject>Response Elements</subject><subject>Stearoyl-CoA Desaturase - genetics</subject><subject>Stearoyl-CoA Desaturase - metabolism</subject><subject>Sterol Regulatory Element Binding Protein 1 - genetics</subject><subject>Sterol Regulatory Element Binding Protein 1 - metabolism</subject><subject>surface plasmon resonance</subject><issn>0263-6484</issn><issn>1099-0844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtuEzEUQC0EomlB4guQl2ym2ONXvGzSpiAFiNJWIDbWHdtDDTPjdOxRifgqfoRvYkLTdsXK0vW5R1cHoVeUHFNCyre2qo8ZkeoJmlCidUGmnD9FE1JKVkg-5QfoMKXvhBAtGXmODkpRSk6lmKBfs9C50H3Dscab2GyHLkEeesje4Rpy3mKwwSWcI15-Wf_5jaFzuI1uaCCH2O3WLtZns1VBceiy78H-G9-GfI0Bp423oQ4WX8xPKd70sY0jg33jW9_lF-hZDU3yL_fvEbpanF3O3xXLT-fv5yfLwjKhVaFsJTwRoDjRimvpK1cBaKUUSMk4aBBqyimwijsmPVGayQocKcFJ5QRlR-jNnXc84GbwKZs2JOubBjofh2SoZHrUyVI8oraPKfW-Nps-tNBvDSVml9qMqc0u9Yi-3luHqvXuAbxvOwLFHXAbGr_9r8jMZ4u9cM-HlP3PBx76H2b8VcJ8_nhuPszWq8V6ujJf2V8pgpdX</recordid><startdate>201412</startdate><enddate>201412</enddate><creator>Caputo, Mariella</creator><creator>De Rosa, Maria Caterina</creator><creator>Rescigno, Tania</creator><creator>Zirpoli, Hylde</creator><creator>Vassallo, Antonio</creator><creator>De Tommasi, Nunziatina</creator><creator>Torino, Gaetano</creator><creator>Tecce, Mario Felice</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>201412</creationdate><title>Binding of polyunsaturated fatty acids to LXRα and modulation of SREBP-1 interaction with a specific SCD1 promoter element</title><author>Caputo, Mariella ; De Rosa, Maria Caterina ; Rescigno, Tania ; Zirpoli, Hylde ; Vassallo, Antonio ; De Tommasi, Nunziatina ; Torino, Gaetano ; Tecce, Mario Felice</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3597-7cb5e05a74097496ebdbaa9777a6634a9a57841a3b4d36e07936bad02ad67d513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>arachidonic acid</topic><topic>docosahexaenoic acid</topic><topic>eicosapentaenoic acid</topic><topic>Fatty Acids, Unsaturated - metabolism</topic><topic>gene expression</topic><topic>Hep G2 Cells</topic><topic>Humans</topic><topic>lipogenic pathways</topic><topic>Liver X Receptors</topic><topic>Orphan Nuclear Receptors - metabolism</topic><topic>Protein Binding</topic><topic>Response Elements</topic><topic>Stearoyl-CoA Desaturase - genetics</topic><topic>Stearoyl-CoA Desaturase - metabolism</topic><topic>Sterol Regulatory Element Binding Protein 1 - genetics</topic><topic>Sterol Regulatory Element Binding Protein 1 - metabolism</topic><topic>surface plasmon resonance</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Caputo, Mariella</creatorcontrib><creatorcontrib>De Rosa, Maria Caterina</creatorcontrib><creatorcontrib>Rescigno, Tania</creatorcontrib><creatorcontrib>Zirpoli, Hylde</creatorcontrib><creatorcontrib>Vassallo, Antonio</creatorcontrib><creatorcontrib>De Tommasi, Nunziatina</creatorcontrib><creatorcontrib>Torino, Gaetano</creatorcontrib><creatorcontrib>Tecce, Mario Felice</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cell biochemistry and function</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Caputo, Mariella</au><au>De Rosa, Maria Caterina</au><au>Rescigno, Tania</au><au>Zirpoli, Hylde</au><au>Vassallo, Antonio</au><au>De Tommasi, Nunziatina</au><au>Torino, Gaetano</au><au>Tecce, Mario Felice</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Binding of polyunsaturated fatty acids to LXRα and modulation of SREBP-1 interaction with a specific SCD1 promoter element</atitle><jtitle>Cell biochemistry and function</jtitle><addtitle>Cell Biochem Funct</addtitle><date>2014-12</date><risdate>2014</risdate><volume>32</volume><issue>8</issue><spage>637</spage><epage>646</epage><pages>637-646</pages><issn>0263-6484</issn><eissn>1099-0844</eissn><abstract>Stearoyl‐CoA desaturase 1 (SCD1) is the rate limiting enzyme in unsaturated fatty acid biosynthesis. This enzyme has an important role in the regulation of hepatic lipogenesis and lipid oxidation, and alterations in these pathways may lead to several diseases. We examined, in HepG2 cell cultures, the mechanism of SCD1 regulation considering the involvement of two transcription factors: liver X receptor alpha (LXRα) and sterol regulatory element‐binding protein‐1 (SREBP‐1), also investigating the effect of dietary polyunsaturated fatty acids (PUFAs) on this process. The analysis of SCD1 promoter allowed to identify a functional SREBP‐1 binding site (SRE 1). LXRα activation increased SCD1 protein level through upregulation of SREBP‐1 and its consequent binding to SRE 1 sequence. Polyunsaturated docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) and arachidonic acid (AA, C20:4) were able to reduce SREBP‐1 binding to SCD1 promoter, while saturated stearic acid (SA, C18:0) did not give any effect. Surface plasmon resonance analysis showed a direct binding of DHA, EPA and AA to LXRα. These data indicate a direct inhibitory interaction of PUFAs with LXRα, a consequent reduction of SREBP‐1 and of its binding to SCD1 promoter. This information provides a mechanism to explain the regulation of lipogenic pathways induced by PUFAs. Copyright © 2014 John Wiley & Sons, Ltd.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>25264165</pmid><doi>10.1002/cbf.3067</doi><tpages>10</tpages></addata></record> |
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| ispartof | Cell biochemistry and function, 2014-12, Vol.32 (8), p.637-646 |
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| subjects | arachidonic acid docosahexaenoic acid eicosapentaenoic acid Fatty Acids, Unsaturated - metabolism gene expression Hep G2 Cells Humans lipogenic pathways Liver X Receptors Orphan Nuclear Receptors - metabolism Protein Binding Response Elements Stearoyl-CoA Desaturase - genetics Stearoyl-CoA Desaturase - metabolism Sterol Regulatory Element Binding Protein 1 - genetics Sterol Regulatory Element Binding Protein 1 - metabolism surface plasmon resonance |
| title | Binding of polyunsaturated fatty acids to LXRα and modulation of SREBP-1 interaction with a specific SCD1 promoter element |
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