1 40 1 Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. URL Address <a href="http://doi.org/10.1042/BJ20141494" target="_blank" rel="noreferrer noopener">http://doi.org/10.1042/BJ20141494</a> Pages 181–193 Issue 2 Volume 470 Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Orphan nuclear receptor oestrogen-related receptor gamma (ERRgamma) plays a key role in hepatic cannabinoid receptor type 1-mediated induction of CYP7A1 gene expression. Publisher An entity responsible for making the resource available The Biochemical journal Date A point or period of time associated with an event in the lifecycle of the resource 2015 2015-09 Subject The topic of the resource Animals; bile acid; Bile Acids and Salts/metabolism; Cannabinoid; cannabinoid receptors; CB1/agonists/genetics/*metabolism; Cells; Cholesterol 7-alpha-Hydroxylase/*biosynthesis/genetics; cholesterol 7alpha-hydroxylase (CYP7A1); Cultured; Cytoplasmic and Nuclear/metabolism; Drug Inverse Agonism; Estrogen/genetics/*metabolism; Ethanol/pharmacology; Gene Expression; Genetic; Glycerides/pharmacology; GSK5182; HEK293 Cells; Hepatocytes/metabolism; Humans; Inbred C57BL; Knockout; Liver/*metabolism; Mice; oestrogen-related receptor gamma (ERRgamma); orphan nuclear receptor; Promoter Regions; Rats; Receptor; Receptors; small heterodimer partner (SHP); Sprague-Dawley; Transcription Creator An entity primarily responsible for making the resource Zhang Yaochen; Kim Don-Kyu; Lee Ji-Min; Park Seung Bum; Jeong Won-Il; Kim Seong Heon; Lee In-Kyu; Lee Chul-Ho; Chiang John Y L; Choi Hueng-Sik Description An account of the resource Bile acids are primarily synthesized from cholesterol in the liver and have important roles in dietary lipid absorption and cholesterol homoeostasis. Detailed roles of the orphan nuclear receptors regulating cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis, have not yet been fully elucidated. In the present study, we report that oestrogen-related receptor gamma (ERRgamma) is a novel transcriptional regulator of CYP7A1 expression. Activation of cannabinoid receptor type 1 (CB1 receptor) signalling induced ERRgamma-mediated transcription of the CYP7A1 gene. Overexpression of ERRgamma increased CYP7A1 expression in vitro and in vivo, whereas knockdown of ERRgamma attenuated CYP7A1 expression. Deletion analysis of the CYP7A1 gene promoter and a ChIP assay revealed an ERRgamma-binding site on the CYP7A1 gene promoter. Small heterodimer partner (SHP) inhibited the transcriptional activity of ERRgamma and thus regulated CYP7A1 expression. Overexpression of ERRgamma led to increased bile acid levels, whereas an inverse agonist of ERRgamma, GSK5182, reduced CYP7A1 expression and bile acid synthesis. Finally, GSK5182 significantly reduced hepatic CB1 receptor-mediated induction of CYP7A1 expression and bile acid synthesis in alcohol-treated mice. These results provide the molecular mechanism linking ERRgamma and bile acid metabolism. Identifier An unambiguous reference to the resource within a given context <a href="http://doi.org/10.1042/BJ20141494" target="_blank" rel="noreferrer noopener">10.1042/BJ20141494</a> Rights Information about rights held in and over the resource Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s). 2015 Animals bile acid Bile Acids and Salts/metabolism Cannabinoid cannabinoid receptors CB1/agonists/genetics/*metabolism Cells Chiang John Y L Choi Hueng-Sik Cholesterol 7-alpha-Hydroxylase/*biosynthesis/genetics cholesterol 7alpha-hydroxylase (CYP7A1) Cultured Cytoplasmic and Nuclear/metabolism Department of Integrative Medical Sciences Drug Inverse Agonism Estrogen/genetics/*metabolism Ethanol/pharmacology Gene Expression Genetic Glycerides/pharmacology GSK5182 HEK293 Cells Hepatocytes/metabolism Humans Inbred C57BL Jeong Won-Il Kim Don-Kyu Kim Seong Heon Knockout Lee Chul-Ho Lee In-Kyu Lee Ji-Min Liver/*metabolism Mice NEOMED College of Medicine oestrogen-related receptor gamma (ERRgamma) orphan nuclear receptor Park Seung Bum Promoter Regions Rats Receptor Receptors small heterodimer partner (SHP) Sprague-Dawley The Biochemical journal Transcription Zhang Yaochen