title: Early induction of pyruvate dehydrogenase kinase 4 by retinoic acids in adipocytes.
abstract: Vitamin A and its metabolites, such as retinoic acids (RA), are related to metabolic diseases, in particular insulin resistance and obesity. Here, we studied the roles of 9-cis RA and all-trans RA on the regulation of pyruvate dehydrogenase kinase 4 (PDK4), an enzyme involved in fatty acid reesterification, which is a crucial metabolic pathway in adipose tissue (AT) lipid homeostasis.
  
  
  
  9-cis RA and all-trans RA treatment of human and murine AT explants, as well as adipocytes (3T3-F442A cell line) induces PDK4 expression both at the mRNA and the protein level, via a transcriptional mechanism. Using site-directed mutagenesis and chomatin immuno-precipitation, we showed that this activation involves two new RA responsive elements in the Pdk4 promoter, RAREa (DR1: -125/-112) and RAREb (DR1: -86/-73), specific to AT. Furthermore, even though endogeneous Pdk4 gene was upregulated by RA in Fao cells, a rat hepatoma cell line, the induction did not occur through the newly found RAREs.
  
  
  
  In this study, we showed that adipocyte PDK4 gene is a new target of the vitamin A derived RA and might participate to the reduced fatty acid efflux from the adipocyte, a step that plays an important role in the developement of metabolic diseases.
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, UFR des Sciences Fondamentales et Biomédicales, Paris, France.|INSERM, UMR 1124, Paris, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Distel
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, UFR des Sciences Fondamentales et Biomédicales, Paris, France.|INSERM, UMR 1124, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cadoudal
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, UFR des Sciences Fondamentales et Biomédicales, Paris, France.|INSERM, UMR 1124, Paris, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Collinet
authors.affiliation: Department of Pharmacology, University of Tennessee Health Science Center, Memphis TN, USA.
authors.forename: Edwards A
authors.initials: EA
authors.lastname: Park
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, UFR des Sciences Fondamentales et Biomédicales, Paris, France.|INSERM, UMR 1124, Paris, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Benelli
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, UFR des Sciences Fondamentales et Biomédicales, Paris, France.|INSERM, UMR 1124, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bortoli
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000077556:Alitretinoin; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000077556:Alitretinoin; D014212:Tretinoin; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4
keywords: Adipose tissue; Glyceroneogenesis; Pyruvate dehydrogenase kinase 4; Retinoic acids