Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration.
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.
Rausch
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ME
Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA.
Weisberg
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Vardhana
P
P
Tortoriello
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DV
D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015687:Cell Hypoxia / Q000502:physiology*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology
D017252:CD3 Complex; D051272:Glucose Transporter Type 1; D051793:Hypoxia-Inducible Factor 1