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

This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/E159    most recent 00629.2006v1 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 Web of Science 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 Web of Science (22) Citing Articles via Google Scholar Google Scholar Articles by Subauste, A. R. Articles by Burant, C. F. Search for Related Content PubMed PubMed Citation Articles by Subauste, A. R. Articles by Burant, C. F.

Role of FoxO1 in FFA-induced oxidative stress in adipocytes

Departments of ¹Internal Medicine and ²Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan

Submitted 20 November 2006 ; accepted in final form 12 March 2007

Reactive oxygen species (ROS) production has recently been established as an essential contributor in the pathogenesis of obesity-associated insulin resistance. The FoxO1 pathway plays a role not only in nutrient sensing but also in regulating ROS production. We exposed adipocytes to free fatty acids (FFA) and demonstrated that FoxO1 protein levels decrease in a dose-dependent manner. The FoxO1 downregulation correlated with an increase in the production of ROS and a proinflammatory adipokine pattern characterized by a decrease in adiponectin and an increase in IL-6, plasminogen activator inhibitor-1, and monocyte chemotactic protein-1 mRNA expression levels. Similarly, a decrease in FoxO1 protein levels was seen in adipocytes of db/db mice compared with controls. Treatment with the sirtuin agonist resveratrol, which translocates FoxO1 to the nucleus, increased FoxO1 protein levels in adipocytes exposed to FFA. This correlated with a decrease in the generation of ROS and a partial reversal of the proinflammatory adipokine pattern. Together these results indicate that the insulin-resistant adipocyte produced by the exposure to a high concentration of fatty acids is characterized by decreased levels of FoxO1. These data also suggest that modulation of the Sirt1/FoxO1 pathway is a potentially useful therapeutic target for the obesity-induced dysfunctional adipocyte.

inflammatory cytokines; insulin resistance; fatty acids

This article has been cited by other articles:

				M. You and C. Q. Rogers Adiponectin: A Key Adipokine in Alcoholic Fatty Liver Experimental Biology and Medicine, August 1, 2009; 234(8): 850 - 859. [Abstract] [Full Text] [PDF]

				N. Bashan, J. Kovsan, I. Kachko, H. Ovadia, and A. Rudich Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species Physiol Rev, January 1, 2009; 89(1): 27 - 71. [Abstract] [Full Text] [PDF]

				J. M. Ajmo, X. Liang, C. Q. Rogers, B. Pennock, and M. You Resveratrol alleviates alcoholic fatty liver in mice Am J Physiol Gastrointest Liver Physiol, October 1, 2008; 295(4): G833 - G842. [Abstract] [Full Text] [PDF]

				K. Takahashi, S. Yamaguchi, T. Shimoyama, H. Seki, K. Miyokawa, H. Katsuta, T. Tanaka, K. Yoshimoto, H. Ohno, S. Nagamatsu, et al. JNK- and I{kappa}B-dependent pathways regulate MCP-1 but not adiponectin release from artificially hypertrophied 3T3-L1 adipocytes preloaded with palmitate in vitro Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E898 - E909. [Abstract] [Full Text] [PDF]