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AMP-activated protein kinase is activated as a consequence of lipolysis in the adipocyte : potential mechanism and physiological relevance

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Title: AMP-activated protein kinase is activated as a consequence of lipolysis in the adipocyte : potential mechanism and physiological relevance
Authors: Gauthier, Marie-Soleil Browse this author
Miyoshi, Hideaki Browse this author →KAKEN DB
Souza, Sandra C. Browse this author
Cacicedo, José M. Browse this author
Saha, Asish K. Browse this author
Greenberg, Andrew S. Browse this author
Ruderman, Neil B. Browse this author
Issue Date: 13-Jun-2008
Publisher: American Society for Biochemistry and Molecular Biology
Journal Title: Journal of biological chemistry
Volume: 283
Issue: 24
Start Page: 16514
End Page: 16524
Publisher DOI: 10.1074/jbc.M708177200
Abstract: AMP-activated protein kinase (AMPK) is activated in adipocytes during exercise and other states in which lipolysis is stimulated. However, the mechanism(s) responsible for this effect and its physiological relevance are unclear. To examine these questions, 3T3-L1 adipocytes were treated with cAMP-inducing agents (isoproterenol, forskolin, and isobutylmethylxanthine), which stimulate lipolysis and activate AMPK. When lipolysis was partially inhibited with the general lipase inhibitor orlistat, AMPK activation by these agents was also partially reduced, but the increases in cAMP levels and cAMP-dependent protein kinase (PKA) activity were unaffected. Likewise, small hairpin RNA-mediated silencing of adipose tissue triglyceride lipase inhibited both forskolin-stimulated lipolysis and AMPK activation but not that of PKA. Forskolin treatment increased the AMP:ATP ratio, and this too was reduced by orlistat. When acyl-CoA synthetase, which catalyzes the conversion of fatty acids to fatty acyl-CoA, was inhibited with triacsin C, the increases in both AMPK activity and AMP:ATP ratio were blunted. Isoproterenol-stimulated lipolysis was accompanied by an increase in oxidative stress, an effect that was quintupled in cells incubated with the AMPK inhibitor compound C. The isoproterenol-induced increase in the AMP:ATP ratio was also much greater in these cells. In conclusion, the results indicate that activation of AMPK in adipocytes by cAMP-inducing agents is a consequence of lipolysis and not of PKA activation. They suggest that AMPK activation in this setting is caused by an increase in the AMP:ATP ratio that appears to be due, at least in part, to the acylation of fatty acids. Finally, this AMPK activation appears to restrain the energy depletion and oxidative stress caused by lipolysis.
Rights: This research was originally published in Journal of Biological Chemistry. Marie-Soleil Gauthier, Hideaki Miyoshi, Sandra C. Souza, José M. Cacicedo, Asish K. Saha, Andrew S. Greenberg, and Neil B. Ruderman. AMP-activated Protein Kinase Is Activated as a Consequence of Lipolysis in the Adipocyte: POTENTIAL MECHANISM AND PHYSIOLOGICAL RELEVANCE. J. Biol. Chem. 2008; 283: 16514-16524. © the American Society for Biochemistry and Molecular Biology.
Type: article
URI: http://hdl.handle.net/2115/67269
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 三好 秀明

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