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Originally published In Press as doi:10.1074/jbc.M414222200 on May 3, 2005

J. Biol. Chem., Vol. 280, Issue 26, 25250-25257, July 1, 2005
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Anti-lipolytic Action of AMP-activated Protein Kinase in Rodent Adipocytes*

Marie Daval{ddagger}§, Francine Diot-Dupuy{ddagger}, Raymond Bazin{ddagger}, Isabelle Hainault{ddagger}, Benoît Viollet¶, Sophie Vaulont¶, Eric Hajduch{ddagger}, Pascal Ferré{ddagger}, and Fabienne Foufelle{ddagger}||

From the {ddagger}INSERM U671, Centre de Recherches Biomédicales des Cordeliers, Université Pierre et Marie Curie, 75270 Paris Cedex 06, France and Institut Cochin, Département de Génétique, Développement et Pathologie Moléculaire, Faculté de Médecine Cochin-Port Royal, 75014 Paris, France

Despite its importance in terms of energy homeostasis, the role of AMP-activated protein kinase in adipose tissue remains controversial. Initial studies have described an anti-lipolytic role for AMP-activated protein kinase, whereas more recent studies have suggested the converse. Thus we have addressed the role of AMP-activated protein kinase in adipose tissue by modulating AMP-activated protein kinase activity in primary rodent adipocytes using pharmacological activators or by adenoviral expression of dominant negative or constitutively active forms of the kinase. We then studied the effects of AMP-activated protein kinase activity modulation on lipolytic mechanisms. Finally, we analyzed the consequences of a genetic deletion of AMP-activated protein kinase in mouse adipocytes. AMP-activated protein kinase activity in adipocytes is represented mainly by the {alpha}1 isoform and is induced by all of the stimuli that increase cAMP in adipocytes, including fasting. When AMP-activated protein kinase activity is increased by 5-aminoimidazole-4-carboxamide-riboside, phenformin, or by the expression of a constitutively active form, isoproterenol-induced lipolysis is strongly reduced. Conversely, when AMP-activated protein kinase activity is decreased either by a dominant negative form or in AMP-activated protein kinase {alpha}1 knock-out mice, lipolysis is increased. We present data suggesting that AMP-activated protein kinase acts on hormone-sensitive lipase by blocking its translocation to the lipid droplet. We conclude that, in mature adipocytes, AMP-activated protein kinase activation has a clear anti-lipolytic effect.


Received for publication, December 17, 2004 , and in revised form, March 22, 2005.

* This work is supported by a grant from Alfediam-Takeda and by two contracts (QLG1-CT-2001-01488, Ampdiamet and LSHM-CT-2004-005272, Exgenesis) from the European commission. 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.

§ Recipient of a doctoral fellowship from the Ministère de l'Enseignement Supérieur et de la Recherche, France.

|| To whom correspondence should be addressed: U671 INSERM, Centre de Recherches Biomédicales des Cordeliers, 15, rue de l'Ecole de Médecine, 75270 Paris Cedex 06, France. Tel.: 33-1-42-34-69-23; Fax: 33-1-40-51-85-86; E-mail: foufelle{at}bhdc.jussieu.fr.


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