title: Anti-lipolytic action of AMP-activated protein kinase in rodent adipocytes.
abstract: 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.
authors.affiliation: INSERM U671, Centre de Recherches Biomédicales des Cordeliers, Université Pierre et Marie Curie, 75270 Paris Cedex 06, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Daval
authors.forename: Francine
authors.initials: F
authors.lastname: Diot-Dupuy
authors.forename: Raymond
authors.initials: R
authors.lastname: Bazin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hainault
authors.forename: Benoît
authors.initials: B
authors.lastname: Viollet
authors.forename: Sophie
authors.initials: S
authors.lastname: Vaulont
authors.forename: Eric
authors.initials: E
authors.lastname: Hajduch
authors.forename: Pascal
authors.initials: P
authors.lastname: Ferré
authors.forename: Fabienne
authors.initials: F
authors.lastname: Foufelle
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases; D000249:Adenosine Monophosphate / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry; D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D015153:Blotting, Western; D002384:Catalysis; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D017353:Gene Deletion; D005799:Genes, Dominant; D006801:Humans; D047468:Immunoprecipitation; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008066:Lipolysis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000378:metabolism*; D010629:Phenformin / Q000737:chemistry; D010766:Phosphorylation; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012263:Ribonucleosides / Q000737:chemistry; D013997:Time Factors
chemical_list: D008055:Lipids; D009097:Multienzyme Complexes; D020033:Protein Isoforms; D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; D000249:Adenosine Monophosphate; C011651:acadesine; D000255:Adenosine Triphosphate; D010629:Phenformin; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human