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Cholic acid mediates negative feedback regulation of bile acid synthesis in mice
Cholesterol is converted into dozens of primary and secondary bile acids through pathways subject to negative feedback regulation mediated by the nuclear receptor farnesoid X receptor (FXR) and other effectors. Disruption of the sterol 12α-hydroxylase gene ( Cyp8b1 ) in mice prevents the synthesis o...
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| Published in: | The Journal of clinical investigation 2002-10, Vol.110 (8), p.1191-1200 |
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| Main Authors: | , , , , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c1659-beda7d124a8cd2af2fa1c93d2c0cb29ec3f3d7b98eec6c23082fd3c3a64faad03 |
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| container_end_page | 1200 |
| container_issue | 8 |
| container_start_page | 1191 |
| container_title | The Journal of clinical investigation |
| container_volume | 110 |
| creator | Li-Hawkins, Jia Gåfvels, Mats Olin, Maria Lund, Erik G. Andersson, Ulla Schuster, Gertrud Björkhem, Ingemar Russell, David W. Eggertsen, Gosta |
| description | Cholesterol is converted into dozens of primary and secondary bile acids through pathways subject to negative feedback regulation mediated by the nuclear receptor farnesoid X receptor (FXR) and other effectors. Disruption of the sterol 12α-hydroxylase gene (
Cyp8b1
) in mice prevents the synthesis of cholate, a primary bile acid, and its metabolites. Feedback regulation of the rate-limiting biosynthetic enzyme cholesterol 7α-hydroxylase (CYP7A1) is lost in
Cyp8b1
–/–
mice, causing expansion of the bile acid pool and alterations in cholesterol metabolism. Expression of other FXR target genes is unaltered in these mice. Cholate restores CYP7A1 regulation in vivo and in vitro. The results implicate cholate as an important negative regulator of bile acid synthesis and provide preliminary evidence for ligand-specific gene activation by a nuclear receptor. |
| doi_str_mv | 10.1172/JCI16309 |
| format | article |
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Cyp8b1
) in mice prevents the synthesis of cholate, a primary bile acid, and its metabolites. Feedback regulation of the rate-limiting biosynthetic enzyme cholesterol 7α-hydroxylase (CYP7A1) is lost in
Cyp8b1
–/–
mice, causing expansion of the bile acid pool and alterations in cholesterol metabolism. Expression of other FXR target genes is unaltered in these mice. Cholate restores CYP7A1 regulation in vivo and in vitro. The results implicate cholate as an important negative regulator of bile acid synthesis and provide preliminary evidence for ligand-specific gene activation by a nuclear receptor.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/JCI16309</identifier><identifier>PMID: 12393855</identifier><language>eng</language><publisher>American Society for Clinical Investigation</publisher><ispartof>The Journal of clinical investigation, 2002-10, Vol.110 (8), p.1191-1200</ispartof><rights>Copyright © 2002, American Society for Clinical Investigation 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1659-beda7d124a8cd2af2fa1c93d2c0cb29ec3f3d7b98eec6c23082fd3c3a64faad03</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC150802/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC150802/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1958552$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Li-Hawkins, Jia</creatorcontrib><creatorcontrib>Gåfvels, Mats</creatorcontrib><creatorcontrib>Olin, Maria</creatorcontrib><creatorcontrib>Lund, Erik G.</creatorcontrib><creatorcontrib>Andersson, Ulla</creatorcontrib><creatorcontrib>Schuster, Gertrud</creatorcontrib><creatorcontrib>Björkhem, Ingemar</creatorcontrib><creatorcontrib>Russell, David W.</creatorcontrib><creatorcontrib>Eggertsen, Gosta</creatorcontrib><title>Cholic acid mediates negative feedback regulation of bile acid synthesis in mice</title><title>The Journal of clinical investigation</title><description>Cholesterol is converted into dozens of primary and secondary bile acids through pathways subject to negative feedback regulation mediated by the nuclear receptor farnesoid X receptor (FXR) and other effectors. Disruption of the sterol 12α-hydroxylase gene (
Cyp8b1
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Cyp8b1
–/–
mice, causing expansion of the bile acid pool and alterations in cholesterol metabolism. Expression of other FXR target genes is unaltered in these mice. Cholate restores CYP7A1 regulation in vivo and in vitro. The results implicate cholate as an important negative regulator of bile acid synthesis and provide preliminary evidence for ligand-specific gene activation by a nuclear receptor.</description><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><recordid>eNpVj81OwzAQhC0EoqEg8Qh-gYB_4sQ-cEARP0WV4ADnaGOvU9M0qeK0qG9PpPbS06xm5htpCbnn7IHzQjx-lAueS2YuSMKV0qkWUl-ShDHBU1NIPSM3Mf4yxrNMZddkxoU0UiuVkK9y1bfBUrDB0Q26ACNG2mEDY9gj9YiuBrumAza7dvL6jvae1qHFIxIP3bjCGCINHd0Ei7fkykMb8e6kc_Lz-vJdvqfLz7dF-bxMLc-VSWt0UDguMtDWCfDCA7dGOmGZrYVBK710RW00os2tkEwL76SVkGcewDE5J-lxN_7hdldX2yFsYDhUPYTqZK2nCytlhGBi6j8d-1My_WmxGwdoz7DzpAurqun3FVdMT_w_VR9ubA</recordid><startdate>20021015</startdate><enddate>20021015</enddate><creator>Li-Hawkins, Jia</creator><creator>Gåfvels, Mats</creator><creator>Olin, Maria</creator><creator>Lund, Erik G.</creator><creator>Andersson, Ulla</creator><creator>Schuster, Gertrud</creator><creator>Björkhem, Ingemar</creator><creator>Russell, David W.</creator><creator>Eggertsen, Gosta</creator><general>American Society for Clinical Investigation</general><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20021015</creationdate><title>Cholic acid mediates negative feedback regulation of bile acid synthesis in mice</title><author>Li-Hawkins, Jia ; Gåfvels, Mats ; Olin, Maria ; Lund, Erik G. ; Andersson, Ulla ; Schuster, Gertrud ; Björkhem, Ingemar ; Russell, David W. ; Eggertsen, Gosta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1659-beda7d124a8cd2af2fa1c93d2c0cb29ec3f3d7b98eec6c23082fd3c3a64faad03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li-Hawkins, Jia</creatorcontrib><creatorcontrib>Gåfvels, Mats</creatorcontrib><creatorcontrib>Olin, Maria</creatorcontrib><creatorcontrib>Lund, Erik G.</creatorcontrib><creatorcontrib>Andersson, Ulla</creatorcontrib><creatorcontrib>Schuster, Gertrud</creatorcontrib><creatorcontrib>Björkhem, Ingemar</creatorcontrib><creatorcontrib>Russell, David W.</creatorcontrib><creatorcontrib>Eggertsen, Gosta</creatorcontrib><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li-Hawkins, Jia</au><au>Gåfvels, Mats</au><au>Olin, Maria</au><au>Lund, Erik G.</au><au>Andersson, Ulla</au><au>Schuster, Gertrud</au><au>Björkhem, Ingemar</au><au>Russell, David W.</au><au>Eggertsen, Gosta</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cholic acid mediates negative feedback regulation of bile acid synthesis in mice</atitle><jtitle>The Journal of clinical investigation</jtitle><date>2002-10-15</date><risdate>2002</risdate><volume>110</volume><issue>8</issue><spage>1191</spage><epage>1200</epage><pages>1191-1200</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><abstract>Cholesterol is converted into dozens of primary and secondary bile acids through pathways subject to negative feedback regulation mediated by the nuclear receptor farnesoid X receptor (FXR) and other effectors. Disruption of the sterol 12α-hydroxylase gene (
Cyp8b1
) in mice prevents the synthesis of cholate, a primary bile acid, and its metabolites. Feedback regulation of the rate-limiting biosynthetic enzyme cholesterol 7α-hydroxylase (CYP7A1) is lost in
Cyp8b1
–/–
mice, causing expansion of the bile acid pool and alterations in cholesterol metabolism. Expression of other FXR target genes is unaltered in these mice. Cholate restores CYP7A1 regulation in vivo and in vitro. The results implicate cholate as an important negative regulator of bile acid synthesis and provide preliminary evidence for ligand-specific gene activation by a nuclear receptor.</abstract><pub>American Society for Clinical Investigation</pub><pmid>12393855</pmid><doi>10.1172/JCI16309</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of clinical investigation, 2002-10, Vol.110 (8), p.1191-1200 |
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| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_592202 |
| source | Open Access: PubMed Central; EZB Electronic Journals Library |
| title | Cholic acid mediates negative feedback regulation of bile acid synthesis in mice |
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