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The clock-controlled proline- and acidic amino acid-rich domain basic leucine zipper proteins D-site-binding protein, thyrotroph embryonic factor, and hepatic leukemia factor have previously been shown to participate in the circadian control of xenobiotic detoxification in liver and other peripheral organs. Here we present genetic and biochemical evidence that the three proline- and acidic amino acid-rich basic leucine zipper proteins also play a key role in circadian lipid metabolism by influencing the rhythmic expression and activity of the nuclear receptor peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1). Our results suggest that, in liver, D-site-binding protein, hepatic leukemia factor, and thyrotroph embryonic factor contribute to the circadian transcription of genes specifying acyl-CoA thioesterases, leading to a cyclic release of fatty acids from thioesters. In turn, the fatty acids act as ligands for PPAR\u03b1, and the activated PPAR\u03b1 receptor then stimulates the transcription of genes encoding proteins involved in the uptake and\/or metabolism of lipids, cholesterol, and glucose metabolism.<\/jats:p>","DOI":"10.1073\/pnas.1002862108","type":"journal-article","created":{"date-parts":[[2011,3,8]],"date-time":"2011-03-08T07:01:21Z","timestamp":1299567681000},"page":"4794-4799","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":79,"title":["Proline- and acidic amino acid-rich basic leucine zipper proteins modulate peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1) activity"],"prefix":"10.1073","volume":"108","author":[{"given":"Fr\u00e9d\u00e9ric","family":"Gachon","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, National Center of Competence in Research \u201cFrontiers in Genetics,\u201d Sciences III, University of Geneva, CH-1211 Geneva 4, Switzerland;"},{"name":"Department of Pharmacology and Toxicology, University of Lausanne, CH-1005 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Leuenberger","sequence":"additional","affiliation":[{"name":"Center for Integrative Genomics, National Center of Competence in Research \u201cFrontiers in Genetics,\u201d University of Lausanne, CH-1015 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Claudel","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine, Medical University Graz, A-8036 Graz, Austria; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Gos","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, National Center of Competence in Research \u201cFrontiers in Genetics,\u201d Sciences III, University of Geneva, CH-1211 Geneva 4, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Jouffe","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Lausanne, CH-1005 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Fleury Olela","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, National Center of Competence in Research \u201cFrontiers in Genetics,\u201d Sciences III, University of Geneva, CH-1211 Geneva 4, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"de Mollerat du Jeu","sequence":"additional","affiliation":[{"name":"Life Technologies, Carlsbad, CA 92008"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Wahli","sequence":"additional","affiliation":[{"name":"Center for Integrative Genomics, National Center of Competence in Research \u201cFrontiers in Genetics,\u201d University of Lausanne, CH-1015 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ueli","family":"Schibler","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, National Center of Competence in Research \u201cFrontiers in Genetics,\u201d Sciences III, University of Geneva, CH-1211 Geneva 4, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,3,7]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806717105"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00025.2005"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.3.1764"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.050"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.183500"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.291.5503.490"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/07853890701491034"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.301404"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.04.015"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39019"},{"key":"e_1_3_3_11_2","first-page":"1013","article-title":"Characterization of the human PPAR\u03b1 promoter: Identification of a functional nuclear receptor response element","volume":"16","author":"Pineda Torra I","year":"2002","unstructured":"I Pineda Torra, Y Jamshidi, DM Flavell, J-C Fruchart, B Staels, Characterization of the human PPAR\u03b1 promoter: Identification of a functional nuclear receptor response element. 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