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Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration
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.
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“Highly cross-linked AGE and melanoidins were predominantly excreted in the faeces while absorbed MRP were in general rapidly excreted by the kidney, with limited accumulation in tissues and organs (465,528 -531) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [530]
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“Obesity is characterized by an overgrowth of adipose tissue that leads to the formation of hypoxic areas within this tissue.”
From Hypoxia decreases insulin signaling pathways in adipocytes. (2009) · cites this paper as [3]
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Goossens, G. H. (2017) · Obesity Facts · doi:10.1159/000471488 · Cited by 8,481
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Sun, K., Kusminski, C. M., & Scherer, P. E. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45887 · Cited by 1,941
Normalization of obesity-associated insulin resistance through immunotherapy
Winer, S., Chan, Y., Paltser, G., Truong, D., Tsui, H., Bahrami, J., Dorfman, R., Wang, Y., Zielenski, J., Mastronardi, F., et al. (2009) · Nature Medicine · doi:10.1038/nm.2001 · Cited by 1,370
Metadata
- Authors
- Rausch, M. E., Weisberg, S., Vardhana, P., & Tortoriello, D. V.
- Affiliations
- Columbia University (US)
- Corresponding author
- Tortoriello, D V
- Venue
- International Journal of Obesity
- Published
- 2007-09-25
- Volume
- 32
- Issue
- 3
- Pages
- 451-463
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W2160915024
- Cited by
- 585
- References
- 64
- Citations by year
- 2026: 7 · 2025: 17 · 2024: 18 · 2023: 19 · 2022: 23 · 2021: 29 · 2020: 28 · 2019: 29 · 2018: 33 · 2017: 50 · 2016: 31 · 2015: 48 · 2014: 42 · 2013: 45 · 2012: 39
- FWCI
- 17.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD001275)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- obesity, adipose tissue inflammation, cytotoxic T lymphocytes, CD8+ T cells, hypoxia-inducible factor, GLUT1, macrophages, F4/80+ macrophages, pimonidazole, ob/ob mice, diet-induced obesity, C57BL/6J mice
- MeSH terms
- Adipose Tissue, Animals, Immunohistochemistry, Macrophages, Male, Mice, Inbred C57BL, Mice, Obese, Obesity, T-Lymphocytes, Cytotoxic, Cell Hypoxia, CD3 Complex, CD8-Positive T-Lymphocytes, Glucose Transporter Type 1, Mice, Hypoxia-Inducible Factor 1
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