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This article is part of the supplement: Metabolism, diet and disease

Open Access Poster presentation

Glucose metabolism is linked to the inflammatory status of macrophages

Amy R Johnson1*, Alex J Freemerman1, E Dale Abel2, Jeffery Rathmell3 and Liza Makowski1

  • * Corresponding author: Amy R Johnson

Author affiliations

1 Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 25799, USA

2 Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah, Salt Lake City, UT 84132 USA

3 Department of Pharmacology and Cancer Biology, Department of Immunology, Sarah W. Stedman Center for Nutrition and Metabolism, Duke University, Durham, NC 27708 USA

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Citation and License

BMC Proceedings 2012, 6(Suppl 3):P62  doi:10.1186/1753-6561-6-S3-P62

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1753-6561/6/S3/P62


Published:1 June 2012

© 2012 Johnson et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

Macrophages infiltrate adipose tissue at the onset of weight gain and directly contribute to adipose inflammation, insulin resistance, and obesity [1]. The type of fuel substrate utilized by macrophages is central to the formation of obesity, a global epidemic [2]. Our goal is to understand the role of macrophage glucose metabolism in the promotion of inflammation and insulin resistance during high fat diet-induced obesity. We hypothesize that macrophages with blunted or elevated glucose metabolism will display limited or exaggerated immune responses, and modulate susceptibility to insulin resistance and obesity, respectively.

Materials and methods

GLUT1 is the glucose transporter expressed by macrophages [3]. We manipulated macrophage glucose metabolism using GLUT1 over-expression and deletion techniques in vitro, ex vivo, and in vivo. In vitro studies involved over-expression of GLUT1 in RAW264.7 cells. A high fat diet-induced obesity model involving a novel macrophage-specific Glut1 knockout mouse (Glut1MΦ-/-) was used to assess total body weight, glucose tolerance, tissue histological alterations, and gene expression changes resulting from Glut1 deletion. Bone marrow-derived macrophages (BMDMs), isolated from Glut1MΦ-/-mice fed a control diet, were used for measures of polarization, and glucose uptake and metabolism.

Results

GLUT1 over-expression resulted in elevated glucose uptake and metabolism, as well as a hyper-inflammatory state characterized by elevated secretion of MCP-1 and PAI-1, all of which could be blunted with a pharmacologic inhibitor of glycolysis. Preliminary data suggests that Glut1MΦ-/- mice fed a high fat diet were resistant to obesity, remained normoglycemic and demonstrated blunted inflammation in liver and adipose. Glut1MΦ-/- BMDMs were viable, but metabolized less glucose at baseline and after LPS stimulation.

Conclusions

The capacity to use glucose as a fuel is correlated to the inflammatory status of macrophages which likely plays an integral role in the promotion of obesity-related insulin resistance. Possible mechanisms linking glucose metabolism to inflammation are being investigated. Understanding macrophage glucose metabolism and inflammation will identify metabolic and/or signaling pathways that will serve as novel therapeutic targets in the treatment of diabetes and obesity.

References

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