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.
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 obesemice. 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 obesemice, 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.
Authors: Charlotte Boydens; Nele Maenhaut; Bart Pauwels; Kelly Decaluwé; Johan Van de Voorde Journal: Curr Hypertens Rep Date: 2012-06 Impact factor: 5.369
Authors: S Caspar-Bauguil; B Cousin; S Bour; L Casteilla; L Castiella; L Penicaud; C Carpéné Journal: J Physiol Biochem Date: 2009-12 Impact factor: 4.158
Authors: A Wree; A Mayer; S Westphal; A Beilfuss; A Canbay; R R Schick; G Gerken; P Vaupel Journal: J Endocrinol Invest Date: 2011-09-27 Impact factor: 4.256