{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:41:05Z","timestamp":1777941665765,"version":"3.51.4"},"reference-count":36,"publisher":"Proceedings of the National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,2,27]]},"abstract":"<jats:p>Peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1) is a key\n regulator of lipid homeostasis in hepatocytes and target for fatty\n acids and hypolipidemic drugs. How these signaling molecules reach the\n nuclear receptor is not known; however, similarities in ligand\n specificity suggest the liver fatty acid binding protein (L-FABP) as a\n possible candidate. In localization studies using laser-scanning\n microscopy, we show that L-FABP and PPAR\u03b1 colocalize in the nucleus\n of mouse primary hepatocytes. Furthermore, we demonstrate by pull-down\n assay and immunocoprecipitation that L-FABP interacts directly with\n PPAR\u03b1. In a cell biological approach with the aid of a mammalian\n two-hybrid system, we provide evidence that L-FABP interacts with\n PPAR\u03b1 and PPAR\u03b3 but not with PPAR\u03b2 and retinoid X receptor-\u03b1 by\n protein\u2013protein contacts. In addition, we demonstrate that the\n observed interaction of both proteins is independent of ligand binding.\n Final and quantitative proof for L-FABP mediation was obtained in\n transactivation assays upon incubation of transiently and stably\n transfected HepG2 cells with saturated, monounsaturated, and\n polyunsaturated fatty acids as well as with hypolipidemic drugs. With\n all ligands applied, we observed strict correlation of PPAR\u03b1 and\n PPAR\u03b3 transactivation with intracellular concentrations of L-FABP.\n This correlation constitutes a nucleus-directed signaling by fatty\n acids and hypolipidemic drugs where L-FABP acts as a cytosolic gateway\n for these PPAR\u03b1 and PPAR\u03b3 agonists. Thus, L-FABP and the respective\n PPARs could serve as targets for nutrients and drugs to affect\n expression of PPAR-sensitive genes.<\/jats:p>","DOI":"10.1073\/pnas.051619898","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:45:09Z","timestamp":1027694709000},"page":"2323-2328","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":423,"title":["Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated receptors \u03b1- and \u03b3-mediated gene expression via liver fatty acid binding protein: A signaling path to the nucleus"],"prefix":"10.1073","volume":"98","author":[{"given":"Christian","family":"Wolfrum","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of M\u00fcnster,\r Wilhelm-Klemm-Strasse 2, 48149 M\u00fcnster, Germany;\r Division of Cell Biology, German Cancer Research Center,\r Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; and\r Institute of Chemical and Biochemical Sensor Research,\r Mendelstrasse 7, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carola M.","family":"Borrmann","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of M\u00fcnster,\r Wilhelm-Klemm-Strasse 2, 48149 M\u00fcnster, Germany;\r Division of Cell Biology, German Cancer Research Center,\r Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; and\r Institute of Chemical and Biochemical Sensor Research,\r Mendelstrasse 7, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torsten","family":"B\u00f6rchers","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of M\u00fcnster,\r Wilhelm-Klemm-Strasse 2, 48149 M\u00fcnster, Germany;\r Division of Cell Biology, German Cancer Research Center,\r Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; and\r Institute of Chemical and Biochemical Sensor Research,\r Mendelstrasse 7, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friedrich","family":"Spener","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of M\u00fcnster,\r Wilhelm-Klemm-Strasse 2, 48149 M\u00fcnster, Germany;\r Division of Cell Biology, German Cancer Research Center,\r Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; and\r Institute of Chemical and Biochemical Sensor Research,\r Mendelstrasse 7, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"341","published-online":{"date-parts":[[2001,2,20]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(95)00093-F"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.9.4312"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.11.6.0007"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.5.2766"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/347645a0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)32150-7"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-4861-4_19"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.6.6049"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.177.4043.56"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4133(199806)100:6<252::AID-LIPI252>3.0.CO;2-9"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1515\/bchm3.1989.370.1.229"},{"key":"e_1_3_3_12_2","first-page":"781","volume":"239","author":"Cannon 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