Original Article

International Journal of Obesity (2008) 32, 451–463; doi:10.1038/sj.ijo.0803744; published online 25 September 2007

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

M E Rausch1, S Weisberg2, P Vardhana1 and D V Tortoriello1,2

  1. 1Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA
  2. 2Division of Molecular Genetics, Department of Pediatrics, Columbia University, New York, NY, USA

Correspondence: Dr DV Tortoriello, Department of Obstetrics and Gynecology, Russ Berrie Medical Science Pavilion, Columbia University Medical Center, The New York Presbyterian Hospital, 1150 St Nicholas Avenue, Room 620, New York, NY 10032, USA. E-mail: dt2016@columbia.edu

Received 6 March 2007; Revised 10 August 2007; Accepted 19 August 2007; Published online 25 September 2007.

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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.

Keywords:

adipose, hypoxia, inflammation, T cells

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