HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 32, 23591-23602, August 10, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/32/23591    most recent M611111200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tordjman, J. Articles by Antoine, B. Search for Related Content PubMed PubMed Citation Articles by Tordjman, J. Articles by Antoine, B. Social Bookmarking                      What's this?

Cytosolic Aspartate Aminotransferase, a New Partner in Adipocyte Glyceroneogenesis and an Atypical Target of Thiazolidinedione^*

Joan Tordjman¹, Stéphanie Leroyer², Geneviève Chauvet, Joëlle Quette, Caroline Chauvet^¶3, Céline Tomkiewicz^¶, Charles Chapron^**, Robert Barouki^¶, Claude Forest^¶, Martine Aggerbeck^¶, and Bénédicte Antoine⁴

From the Inserm U530 and ^¶Inserm U747, Université Paris Descartes, F-75006, Paris and ^**AP-HP Groupe Hospitalier Universitaire Ouest, CHU Cochin, Université Paris Descartes, F-75006, Paris, and Inserm U680, Université Pierre et Marie Curie-Paris 6, F-75012 Paris, and ^¶CNRS, UPR 9078, F-75015 Paris, France

We show that cytosolic aspartate aminotransferase (cAspAT) is involved in adipocyte glyceroneogenesis, a regulated pathway that controls fatty acid homeostasis by promoting glycerol 3-phosphate formation for fatty acid re-esterification during fasting. cAspAT activity, as well as the incorporation of [¹⁴C]aspartate into the neutral lipid fraction of 3T3-F442A adipocytes was stimulated by the thiazolidinedione (TZD) rosiglitazone. Conversely, the ratio of fatty acid to glycerol released into the medium decreased. Regulation of cAspAT gene expression was specific to differentiated adipocytes and did not require any peroxisome proliferator-activated receptor (PPAR)/retinoid X receptor- direct binding. Nevertheless, PPAR is indirectly necessary for both cAspAT basal expression and TZD responsiveness because they are, respectively, diminished and abolished by ectopic overexpression of a dominant negative PPAR. The cAspAT TZD-responsive site was restricted to a single AGGACA hexanucleotide located at -381 to -376 bp whose mutation impaired the specific ROR binding. ROR ectopic expression activated the cAspAT gene transcription in absence of rosiglitazone, and its protein amount in nuclear extracts is 1.8-fold increased by rosiglitazone treatment of adipocytes. Finally, the amounts of ROR and cAspAT mRNAs were similarly increased by TZD treatment of human adipose tissue explants, confirming coordinated regulation. Our data identify cAspAT as a new member of glyceroneogenesis, transcriptionally regulated by TZD via the control of ROR expression by PPAR in adipocytes.

Received for publication, December 4, 2006 , and in revised form, May 22, 2007.

^* This work was supported in part by INSERM, CNRS, the Université René Descartes, the Association Claude Bernard, and the Association pour la Recherche contre le Cancer. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Recipient of a fellowship from the Ministère de l'Education Nationale et de la Recherche and of the 2003 prize from the French Nutrition Society. Present address: INSERM U755, Paris F-75004, France.

² Recipient of a fellowship from the Agence Nationale pour la Recherche sur le Sida.

³ Supported by Association pour la Recherche contre le Cancer Grant 3511 (to J.-L. Danan).

⁴ To whom correspondence should be addressed: INSERM U680, Université Pierre et Marie Curie, Facultéde Médecine, 27, rue de Chaligny, 75012 Paris, France. Tel.: 33-1-4001-1351; Fax: 33-1-4001-1352; E-mail: antoine{at}st-antoine.inserm.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?