title: Retinoids synergized with insulin to induce Srebp-1c expression and activated its promoter via the two liver X receptor binding sites that mediate insulin action.
abstract: We have reported that the rat liver lipophilic extract (LE) synergized with insulin to induce Gck and Srebp-1c in primary rat hepatocytes. After identification of retinol and retinal in LE, only their effects in the absence or presence of insulin on Gck, but not that on Srebp-1c, were investigated subsequently. The retinoid effects on the Srebp-1c expression and the activation of its promoter were examined with real-time PCR and reporter gene assays, respectively. In primary hepatocytes, retinal and retinoic acid (RA) synergized with insulin to induce Srebp-1c expression. This induction was followed by the elevation of its target gene, fatty acid synthase. Activation of retinoid X receptor, but not retinoic acid receptor, was responsible for the induction of Srebp-1c expression. RA, but not retinal, also induced Srebp-1c expression in a dose dependent manner in INS-1 cells. The RA responsive elements in Srebp-1c promoter were determined as previously identified two liver X receptor elements responsible for mediating insulin action. We conclude that retinoids regulate hepatic Srebp-1c expression through activation of retinoid X receptor. The RA- and insulin-induced Srebp-1c expression converged at the same sites in its promoter, indicating the roles of vitamin A in regulation of hepatic gene expression.
authors.affiliation: Department of Nutrition, University of Tennessee at Knoxville, Knoxville, TN 37996, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guoxun
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D001665:Binding Sites; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects; D012172:Retinaldehyde / Q000494:pharmacology; D047488:Retinoid X Receptors / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism* / Q000494:pharmacology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology; D019014:fas Receptor / Q000235:genetics
chemical_list: D007328:Insulin; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D051780:Sterol Regulatory Element Binding Protein 1; D019014:fas Receptor; D014212:Tretinoin; D012172:Retinaldehyde