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: db06-1491v1 56/7/1761    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cani, P. D. Articles by Burcelin, R. Search for Related Content PubMed PubMed Citation Articles by Cani, P. D. Articles by Burcelin, R. Social Bookmarking                What's this?

Metabolic Endotoxemia Initiates Obesity and Insulin Resistance

¹ Institute of Molecular Medicine, I2MR Toulouse, France
² Unité Pharmacokinetics, Metabolism, Nutrition, and Toxicology-73/69, Université catholique de Louvain, Brussels, Belgium
³ Institut National de la Santé et de la Recherche Médicale (INSERM) 558, Toulouse, France
⁴ INSERM U 626, Marseille, France
⁵ Food Microbial Sciences Unit, Department of Food Biosciences, University of Reading, Reading, U.K
⁶ Unité Mixte de Recherche 5241, Centre National de la Recherche Scientifique, Université Paul Sabatier, Toulouse, France
⁷ Physiogenex S.A.S., Labège Innopole, France
⁸ INSERM U 568, Nice, France

Address correspondence and reprint requests to Rémy Burcelin, I2MR U858, IFR 31, Hôpital Rangueil, BP 84225, Toulouse 31432 Cedex 4, France. E-mail: burcelin{at}toulouse.inserm.fr

Abbreviations: IKK, inhibitor of B kinase; IL, interleukin; LPS, lipopolysaccharide; PAI, plasminogen activator inhibitor; TLR4, toll-like receptor 4; TNF, tumor necrosis factor

Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endotoxemia increased or decreased during the fed or fasted state, respectively, on a nutritional basis and that a 4-week high-fat diet chronically increased plasma LPS concentration two to three times, a threshold that we have defined as metabolic endotoxemia. Importantly, a high-fat diet increased the proportion of an LPS-containing microbiota in the gut. When metabolic endotoxemia was induced for 4 weeks in mice through continuous subcutaneous infusion of LPS, fasted glycemia and insulinemia and whole-body, liver, and adipose tissue weight gain were increased to a similar extent as in high-fat–fed mice. In addition, adipose tissue F4/80-positive cells and markers of inflammation, and liver triglyceride content, were increased. Furthermore, liver, but not whole-body, insulin resistance was detected in LPS-infused mice. CD14 mutant mice resisted most of the LPS and high-fat diet–induced features of metabolic diseases. This new finding demonstrates that metabolic endotoxemia dysregulates the inflammatory tone and triggers body weight gain and diabetes. We conclude that the LPS/CD14 system sets the tone of insulin sensitivity and the onset of diabetes and obesity. Lowering plasma LPS concentration could be a potent strategy for the control of metabolic diseases.

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

This article has been cited by other articles:

				R. Rodriguez-Calvo, L. Serrano, T. Coll, N. Moullan, R. M. Sanchez, M. Merlos, X. Palomer, J. C. Laguna, L. Michalik, W. Wahli, et al. Activation of Peroxisome Proliferator-Activated Receptor {beta}/{delta} Inhibits Lipopolysaccharide-Induced Cytokine Production in Adipocytes by Lowering Nuclear Factor-{kappa}B Activity via Extracellular Signal-Related Kinase 1/2 Diabetes, August 1, 2008; 57(8): 2149 - 2157. [Abstract] [Full Text] [PDF]

				P. D. Cani, R. Bibiloni, C. Knauf, A. Waget, A. M. Neyrinck, N. M. Delzenne, and R. Burcelin Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet-Induced Obesity and Diabetes in Mice Diabetes, June 1, 2008; 57(6): 1470 - 1481. [Abstract] [Full Text] [PDF]

				Y. Li, C. Jiang, G. Xu, N. Wang, Y. Zhu, C. Tang, and X. Wang Homocysteine Upregulates Resistin Production From Adipocytes In Vivo and In Vitro Diabetes, April 1, 2008; 57(4): 817 - 827. [Abstract] [Full Text] [PDF]

				T. Saito, H. Hayashida, and R. Furugen Comment on: Cani et al. (2007) Metabolic Endotoxemia Initiates Obesity and Insulin Resistance: Diabetes 56:1761 1772 Diabetes, December 1, 2007; 56(12): e20 - e20. [Full Text] [PDF]

				R. Burcelin, P. D. Cani, and J. Amar Response to Comment on: Cani et al. (2007) Metabolic Endotoxemia Initiates Obesity and Insulin Resistance: Diabetes 56:1761 1772 Diabetes, December 1, 2007; 56(12): e21 - e21. [Full Text] [PDF]

				C. Cabou, P. D. Cani, G. Campistron, C. Knauf, C. Mathieu, C. Sartori, J. Amar, U. Scherrer, and R. Burcelin Central Insulin Regulates Heart Rate and Arterial Blood Flow: An Endothelial Nitric Oxide Synthase Dependent Mechanism Altered During Diabetes Diabetes, December 1, 2007; 56(12): 2872 - 2877. [Abstract] [Full Text] [PDF]

				C. Erridge, T. Attina, C. M Spickett, and D. J Webb A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation Am. J. Clinical Nutrition, November 1, 2007; 86(5): 1286 - 1292. [Abstract] [Full Text] [PDF]