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Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration

International Journal of Obesity volume 32, pages 451–463 (2008)Cite this article

Abstract

Background:

Obesity is currently viewed as a state of chronic low-grade inflammation in which there is a pro-inflammatory alteration in the serum adipocytokine profile as well as an infiltration of white adipose tissue by activated macrophages. The etiology of this inflammation, however, is poorly understood.

Methods:

Hypothesizing that local hypoxia within expanding white adipose tissue depots may contribute to obesity-related inflammation, we compared body composition, serum inflammatory marker concentrations and the expression of several hypoxia-regulated genes in white adipose tissue derived from lean, dietary-induced obese (DIO) and ob/ob male C57BL/6J mice. We also examined white adipose tissue for the presence of hypoxia using both a pimonidazole-based antibody system and a fiberoptic sensor for real-time pO2 quantification in vivo. Finally, using cell-specific leukocyte antibodies, we performed immunohistochemistry and flow cytometric analyses to further characterize the cellular nature of adipose inflammation.

Results:

We determined that obesity in male C57BL/6J mice is associated with increased expression of HIF (hypoxia-inducible factor) isoforms and GLUT-1, and that white adipose tissue hypoxia was present in the obese mice. Immunohistochemistry revealed hypoxic areas to colocalize predominantly with F4/80+ macrophages. Interestingly, CD3+ T cells were present in large numbers within the adipose of both DIO and ob/ob obese mice, and flow cytometry revealed their adipose to possess significantly more CD8+ T cells than their lean cohort.

Conclusions:

White adipose hypoxia and cytotoxic T-cell invasion are features of obesity in C57BL/6J mice and are potential contributors to their local and generalized inflammatory state.

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Acknowledgements

This work was supported by a Women's Reproductive Health Research Scholarship, NIH 5 K12 HD001275-04 (DVT).

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Authors and Affiliations

  1. Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA

    M E Rausch, P Vardhana & D V Tortoriello

  2. Division of Molecular Genetics, Department of Pediatrics, Columbia University, New York, NY, USA

    S Weisberg & D V Tortoriello

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  1. M E Rausch
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  2. S Weisberg
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Correspondence to D V Tortoriello.

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Rausch, M., Weisberg, S., Vardhana, P. et al. Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obes 32, 451–463 (2008). https://doi.org/10.1038/sj.ijo.0803744

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