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

J. Biol. Chem., Vol. 282, Issue 37, 26793-26801, September 14, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/37/26793    most recent M703701200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by An, Z. Articles by Zou, M.-H. Search for Related Content PubMed PubMed Citation Articles by An, Z. Articles by Zou, M.-H. Social Bookmarking                      What's this?

Nicotine-induced Activation of AMP-activated Protein Kinase Inhibits Fatty Acid Synthase in 3T3L1 Adipocytes

A ROLE FOR OXIDANT STRESS^*

Zhibo An¹, Hong Wang¹, Ping Song¹, Miao Zhang, Xuemei Geng, and Ming-Hui Zou²

From the Vascular Biology Laboratory, Department of Surgery, Graduate School of Medicine, University of Tennessee, Knoxville, Tennessee 37922 and the Division of Endocrinology and Diabetes, Department of Medicine, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104

Recent studies suggest that the AMP-activated protein kinase (AMPK) acts as a major energy sensor and regulator in adipose tissues. The objective of this study was to investigate the role of AMPK in nicotine-induced lipogenesis and lipolysis in 3T3L1 adipocytes. Exposure of 3T3L1 adipocytes to smoking-related concentrations of nicotine increased lipolysis and inhibited fatty acid synthase (FAS) activity in a time- and dose-dependent manner. The effects of nicotine on FAS activity were accompanied by phosphorylation of both AMPK (Thr¹⁷²) and acetyl-CoA carboxylase (ACC; Ser⁷⁹). Nicotine-induced AMPK phosphorylation appeared to be mediated by reactive oxygen species based on the finding that nicotine significantly increased superoxide anions and 3-nitrotyrosine-positive proteins, exogenous peroxynitrite (ONOO^–) mimicked the effects of nicotine on AMPK, and N-acetylcysteine (NAC) abolished nicotine-enhanced AMPK phosphorylation. Inhibition of AMPK using either pharmacologic (insulin, compound C) or genetic means (overexpression of dominant negative AMPK; AMPK-DN) abolished FAS inhibition induced by nicotine or ONOO^–. Conversely, activation of AMPK by pharmacologic (nicotine, ONOO^–, metformin, and AICAR) or genetic (overexpression of constitutively active AMPK) means inhibited FAS activity. Notably, AMPK activation increased threonine phosphorylation of FAS, and this effect was blocked by adenovirus encoding dominant negative AMPK. Finally, AMPK-dependent FAS phosphorylation was confirmed by ³²P incorporation into FAS in adipocytes. Taken together, our results strongly suggest that nicotine, via ONOO^– activates AMPK, resulting in enhanced threonine phosphorylation and consequent inhibition of FAS.

Received for publication, May 4, 2007 , and in revised form, July 16, 2007.

^* This work was supported by National Institutes of Health Grants HL079584, HL080499, and HL074399 and a research award from the Research Management Group, Philip Morris International, Inc. 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 These authors contributed equally to this article.

² To whom correspondence should be addressed: BSEB 325, 941, Stanton L. Young Blvd., Oklahoma City, OK 73104. Tel.: 405-271-3974; Fax: 405-271-3973; E-mail: ming-hui-zou{at}ouhsc.edu.

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

This article has been cited by other articles:

				M.-S. Gauthier, H. Miyoshi, S. C. Souza, J. M. Cacicedo, A. K. Saha, A. S. Greenberg, and N. B. Ruderman AMP-activated Protein Kinase Is Activated as a Consequence of Lipolysis in the Adipocyte: POTENTIAL MECHANISM AND PHYSIOLOGICAL RELEVANCE J. Biol. Chem., June 13, 2008; 283(24): 16514 - 16524. [Abstract] [Full Text] [PDF]