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: 292/1/E166    most recent 00284.2006v1 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 (31) Citing Articles via Google Scholar Google Scholar Articles by Lumeng, C. N. Articles by Saltiel, A. R. Search for Related Content PubMed PubMed Citation Articles by Lumeng, C. N. Articles by Saltiel, A. R.

Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins

¹Life Sciences Institute, Departments of Internal Medicine and Physiology, University of Michigan, and ²Department of Pediatrics and Communicable Diseases, University of Michigan Medical Center, Ann Arbor, Michigan

Submitted 15 June 2006 ; accepted in final form 21 August 2006

Obesity leads to a proinflammatory state with immune responses that include infiltration of adipose tissue with macrophages. These macrophages are believed to alter insulin sensitivity in adipocytes, but the mechanisms that underlie this effect have not been characterized. We have explored the interaction between macrophages and adipocytes in the context of both indirect and direct coculture. Macrophage-secreted factors blocked insulin action in adipocytes via downregulation of GLUT4 and IRS-1, leading to a decrease in Akt phosphorylation and impaired insulin-stimulated GLUT4 translocation to the plasma membrane. GLUT1 was upregulated with a concomitant increase in basal glucose uptake. These changes recapitulate those seen in adipose tissue from insulin-resistant humans and animal models. TNF--neutralizing antibodies partially reversed the insulin resistance produced by macrophage-conditioned media. Peritoneal macrophages and macrophage-enriched stromal vascular cells from adipose tissue also attenuated responsiveness to insulin in a manner correlating with inflammatory cytokine secretion. Adipose tissue macrophages from obese mice have an F4/80⁺CD11b⁺CD68⁺CD14^– phenotype and form long cellular extensions in culture. Peritoneal macrophages take on similar characteristics in direct coculture with adipocytes and induce proinflammatory cytokines, suggesting that macrophage activation state is influenced by contact with adipocytes. Thus both indirect/secreted and direct/cell contact-mediated factors derived from macrophages influence insulin sensitivity in adipocytes.

adipose tissue macrophages; insulin resistance; insulin signaling; obesity

This article has been cited by other articles:

				Z.-b. Deng, A. Poliakov, R. W. Hardy, R. Clements, C. Liu, Y. Liu, J. Wang, X. Xiang, S. Zhang, X. Zhuang, et al. Adipose Tissue Exosome-Like Vesicles Mediate Activation of Macrophage-Induced Insulin Resistance Diabetes, November 1, 2009; 58(11): 2498 - 2505. [Abstract] [Full Text] [PDF]

				D.-E. Lee, S. Kehlenbrink, H. Lee, M. Hawkins, and J. S. Yudkin Getting the message across: mechanisms of physiological cross talk by adipose tissue Am J Physiol Endocrinol Metab, June 1, 2009; 296(6): E1210 - E1229. [Abstract] [Full Text] [PDF]

				A. S. Molgat, A. Gagnon, and A. Sorisky Preadipocyte apoptosis is prevented by macrophage-conditioned medium in a PDGF-dependent manner Am J Physiol Cell Physiol, April 1, 2009; 296(4): C757 - C765. [Abstract] [Full Text] [PDF]

				E. Ortega Martinez de Victoria, X. Xu, J. Koska, A. M. Francisco, M. Scalise, A. W. Ferrante Jr., and J. Krakoff Macrophage Content in Subcutaneous Adipose Tissue: Associations With Adiposity, Age, Inflammatory Markers, and Whole-Body Insulin Action in Healthy Pima Indians Diabetes, February 1, 2009; 58(2): 385 - 393. [Abstract] [Full Text] [PDF]

				V. Samokhvalov, P. J. Bilan, J. D. Schertzer, C. N. Antonescu, and A. Klip Palmitate- and lipopolysaccharide-activated macrophages evoke contrasting insulin responses in muscle cells Am J Physiol Endocrinol Metab, January 1, 2009; 296(1): E37 - E46. [Abstract] [Full Text] [PDF]

				A. Kennedy, K. Martinez, C.-C. Chuang, K. LaPoint, and M. McIntosh Saturated Fatty Acid-Mediated Inflammation and Insulin Resistance in Adipose Tissue: Mechanisms of Action and Implications J. Nutr., January 1, 2009; 139(1): 1 - 4. [Abstract] [Full Text] [PDF]

				C. N. Lumeng, J. B. DelProposto, D. J. Westcott, and A. R. Saltiel Phenotypic Switching of Adipose Tissue Macrophages With Obesity Is Generated by Spatiotemporal Differences in Macrophage Subtypes Diabetes, December 1, 2008; 57(12): 3239 - 3246. [Abstract] [Full Text] [PDF]

				V. Kaddai, T. Gonzalez, M. Bolla, Y. Le Marchand-Brustel, and M. Cormont The nitric oxide-donating derivative of acetylsalicylic acid, NCX 4016, stimulates glucose transport and glucose transporters translocation in 3T3-L1 adipocytes Am J Physiol Endocrinol Metab, July 1, 2008; 295(1): E162 - E169. [Abstract] [Full Text] [PDF]