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

Int J Obes (Lond). 2008 Mar;32(3):451-63. doi: 10.1038/sj.ijo.0803744. Epub 2007 Sep 25.

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 pO(2) 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue / metabolism*
  • Adipose Tissue / pathology
  • Animals
  • CD3 Complex / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Hypoxia / physiology*
  • Glucose Transporter Type 1 / metabolism
  • Hypoxia-Inducible Factor 1 / metabolism
  • Immunohistochemistry
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / immunology*
  • Obesity / metabolism
  • Obesity / physiopathology
  • T-Lymphocytes, Cytotoxic / physiology

Substances

  • CD3 Complex
  • Glucose Transporter Type 1
  • Hypoxia-Inducible Factor 1