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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]
Citations
Cites
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041
Self-citationAdipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760
Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001
Mokdad, A. H., Ford, E. S., Bowman, B. A., Dietz, W. H., Vinicor, F., Bales, V. S., & Marks, J. S. (2003) · JAMA · doi:10.1001/jama.289.1.76 · Cited by 5,866
Inflammation, stress, and diabetes
Wellen, K. E., & Hotamisligil, G. S. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25102 · Cited by 4,143
A central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359
Adipocytokines: mediators linking adipose tissue, inflammation and immunity
Tilg, H., & Moschen, A. R. (2006) · Nature reviews. Immunology · doi:10.1038/nri1937 · Cited by 3,272
The Continuing Epidemics of Obesity and Diabetes in the United States
Mokdad, A. H. (2001) · JAMA · doi:10.1001/jama.286.10.1195 · Cited by 2,730
Cinti, S., Mitchell, G., Barbatelli, G., Murano, I., Ceresi, E., Faloia, E., Wang, S., Fortier, M., Greenberg, A. S., & Obin, M. S. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m500294-jlr200 · Cited by 2,529
Spear, B. A., Winick, M., Phillips, C., & Wilfley, D. E. (1975) · Cited by 2,495
HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption
Papandreou, I., Cairns, R. A., Fontana, L., Lim, A. L., & Denko, N. C. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.012 · Cited by 2,267
Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB
Cai, D., Yuan, M., Frantz, D. F., Melendez, P. A., Hansen, L., Lee, J., & Shoelson, S. E. (2005) · Nature Medicine · doi:10.1038/nm1166 · Cited by 2,245
Adipose Tissue, Inflammation, and Cardiovascular Disease
Berg, A. H., & Scherer, P. E. (2005) · Circulation Research · doi:10.1161/01.res.0000163635.62927.34 · Cited by 2,113
HIF-1α is essential for myeloid cell-mediated inflammation
Cramer, T., Yamanishi, Y., Clausen, B. E., Förster, I., Pawlinski, R., Mackman, N., Haase, V. H., Jaenisch, R., Corr, M., Nizet, V., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00154-5 · Cited by 2,046
Yuan, M., Konstantopoulos, N., Lee, J., Hansen, L., Li, Z.-W., Karin, M., & Shoelson, S. E. (2001) · Science · doi:10.1126/science.1061620 · Cited by 1,884
HIF-1: mediator of physiological and pathophysiological responses to hypoxia
Semenza, G. L. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.4.1474 · Cited by 1,822
IKK-β links inflammation to obesity-induced insulin resistance
Arkan, M. C., Hevener, A. L., Greten, F. R., Maeda, S., Li, Z.-W., Long, J. M., Wynshaw-Boris, A., Poli, G., Olefsky, J., & Karin, M. (2005) · Nature Medicine · doi:10.1038/nm1185 · Cited by 1,773
Molecular mediators of hepatic steatosis and liver injury
Browning, J. D., & Horton, J. D. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200422422 · Cited by 1,772
Fried, S. K., Bunkin, D. A., & Greenberg, A. S. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.3.4660 · Cited by 1,756
Helmlinger, G., Yuan, F., Dellian, M., & Jain, R. K. (1997) · Nature Medicine · doi:10.1038/nm0297-177 · Cited by 1,651
CCR2 modulates inflammatory and metabolic effects of high-fat feeding
Weisberg, S. P., Hunter, D., Huber, R., Lemieux, J., Slaymaker, S., Vaddi, K., Charo, I., Leibel, R. L., & Jr., A. W. F. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24335 · Cited by 1,497
Self-citationCCR2 modulates inflammatory and metabolic effects of high-fat feeding
Weisberg, S. P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24335c1 · Cited by 1,425
Self-citationInflammation and Activated Innate Immunity in the Pathogenesis of Type 2 Diabetes
Pickup, J. C. (2004) · Diabetes Care · doi:10.2337/diacare.27.3.813 · Cited by 1,414
Leptin regulates proinflammatory immune responses
Loffreda, S., Yang, S., Lin, H., Karp, C. L., Brengman, M. L., Wang, D., Klein, A. S., Bulkley, G. B., Bao, C., Noble, P. W., et al. (1998) · The FASEB Journal · doi:10.1096/fasebj.12.1.57 · Cited by 1,264
Cancello, R., Henegar, C., Viguerie, N., Taleb, S., Poitou, C., Rouault, C., Coupaye, M., Pelloux, V., Hugol, D., Bouillot, J.-L., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.8.2277 · Cited by 1,164
The Obesity Epidemic: Pathophysiology and Consequences of Obesity
Pi‐Sunyer, F. X. (2002) · Obesity Research · doi:10.1038/oby.2002.202 · Cited by 885
Metformin reverses fatty liver disease in obese, leptin-deficient mice.
Lin, H. Z., Yang, S. Q., Chuckaree, C., Kuhajda, F., Ronnet, G., & Diehl, A. M. (2000) · Nature Medicine · doi:10.1038/79697 · Cited by 673
Overweight exceeds underweight among women in most developing countries
Méndez, M. A., Monteiro, C. A., & Popkin, B. M. (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.3.714 · Cited by 635
From Blood Monocytes to Adipose Tissue-Resident Macrophages
Curat, C. A., Miranville, A., Sengenès, C., Diehl, M., Tonus, C., Busse, R., & Bouloumié, A. (2004) · Diabetes · doi:10.2337/diabetes.53.5.1285 · Cited by 600
Silha, J. V., Kršek, M., Škrha, J., Sucharda, P., Nyomba, B. L. G., & Murphy, L. (2003) · European Journal of Endocrinology · doi:10.1530/eje.0.1490331 · Cited by 595
Speiser, P., RUDOLF, M. C. J., Anhalt, H., Camacho‐Hübner, C., Chiarelli, F., Eliakim, A., Freemark, M., Grüters, A., Hershkovitz, E., Iughetti, L., et al. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1389 · Cited by 579
Leek, R., Landers, R. J., Harris, A. L., & Lewis, C. E. (1999) · British Journal of Cancer · doi:10.1038/sj.bjc.6690158 · Cited by 450
Consensus statement : Childhood obesity
Speiser, P., RUDOLF, M. C. J., Anhalt, H., Camacho‐Hübner, C., Chiarelli, F., Freemark, M., Grüters, A., Hershkovitz, E., Krude, H., Latzer, Y., et al. (2005) · Cited by 394
Hypoxia-inducible factors in the kidney
Haase, V. H. (2006) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00071.2006 · Cited by 334
Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1
Skurk, T., & Hauner, H. (2004) · International Journal of Obesity · doi:10.1038/sj.ijo.0802778 · Cited by 303
Hypoxia-Induced Gene Expression in Human Macrophages
Burke, B., Giannoudis, A., Corke, K. P., Gill, D., Wells, M., Ziegler-Heitbrock, L., & Lewis, C. E. (2003) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63483-9 · Cited by 286
Braun, R. D., Lanzen, J. L., Snyder, S. A., & Dewhirst, M. W. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.280.6.h2533 · Cited by 285
Hypoxia-inducible Factor 1 Transactivates the Human Leptin Gene Promoter
Grosfeld, A., André, J., Mouzon, S. H., Berra, E., Pouysségur, J., & Guerre-Millo, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206775200 · Cited by 263
Bastard, J.-P., Jardel, C., Delattre, J., Hainque, B., Bruckert, E., & Oberlin, F. (1999) · Circulation · doi:10.1161/circ.99.16.2219/c · Cited by 244
Relation between Age of Onset of Obesity and Size and Number of Adipose Cells
Brook, C. G. D., Lloyd, J. K., & Wolf, O. (1972) · BMJ · doi:10.1136/bmj.2.5804.25 · Cited by 214
Tsatsanis, C., Zacharioudaki, V., Androulidaki, A., Dermitzaki, E., Charalampopoulos, I., MINAS, V., Gravanis, A., & Margioris, A. N. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.07.197 · Cited by 203
The OxyLite: a fibre-optic oxygen sensor.
Griffiths, J. R., & Robinson, S. P. (1999) · British Journal of Radiology · doi:10.1259/bjr.72.859.10624317 · Cited by 186
Discovery and Pharmacological Characterization of a Novel Rodent-Active CCR2 Antagonist, INCB3344
Brodmerkel, C. M., Huber, R., Covington, M. B., Diamond, S., Hall, L. M., Collins, R. J., Leffet, L., Gallagher, K., Feldman, P., Collier, P., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.8.5370 · Cited by 186
Gleadle, J., & Ratcliffe, P. J. (1997) · Blood · doi:10.1182/blood.v89.2.503 · Cited by 182
Among inflammation and coagulation markers, PAI-1 is a true component of the metabolic syndrome
Mertens, I. L., Verrijken, A., Michiels, J. J., van der Planken, M., Ruige, J. B., & Gaal, L. F. V. (2006) · International Journal of Obesity · doi:10.1038/sj.ijo.0803189 · Cited by 176
Hoogeveen, R. C., Morrison, A. C., Boerwinkle, E., MILES, J., Rhodes, C. E., SHARRETT, A., & Ballantyne, C. M. (2005) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2005.03.007 · Cited by 147
Nordsmark, M., Loncaster, J. A., Aquino‐Parsons, C., Chou, S.-C., Gebski, V., West, C., Lindegaard, J. C., Havsteen, H., Davidson, S. E., Hunter, R. D., et al. (2006) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2006.07.010 · Cited by 105
Yaromina, A., Zips, D., Thames, H. D., Eicheler, W., Krause, M., Rosner, A., Haase, M., Petersen, C., Raleigh, J. A., Quennet, V., et al. (2006) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2006.08.010 · Cited by 100
Hypoxia and Expression of Hypoxia-Inducible Factor in the Aging Kidney
Tanaka, T., Kato, H., Kojima, I., Ohse, T., Son, D., Tawakami, T., Yatagawa, T., Inagi, R., Fujita, T., & Nangaku, M. (2006) · The Journals of Gerontology Series A · doi:10.1093/gerona/61.8.795 · Cited by 97
Janković, B., Aquino‐Parsons, C., Raleigh, J. A., Stanbridge, E. J., Durand, R. E., Banáth, J. P., MacPhail, S. H., & Olive, P. L. (2006) · Cytometry Part B Clinical Cytometry · doi:10.1002/cyto.b.20086 · Cited by 87
Adipose tissue dysfunction in obesity and lipodystrophy
Garg, A. (2006) · Clinical cornerstone · doi:10.1016/s1098-3597(06)80039-6 · Cited by 80
Troost, E. G. C., Laverman, P., Kaanders, J. H. A. M., Philippens, M. E. P., Lok, J., Oyen, W. J. G., van der Kogel, A. J., Boerman, O. C., & Bussink, J. (2006) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2006.07.023 · Cited by 70
Assessment of the anti-obesity effects of the TNP-470 analog, CKD-732
Kim, Y. M., An, J. J., Jin, Y. J., Rhee, Y., Soo, B., Lee, H. C., & Lim, S.-K. (2007) · Journal of Molecular Endocrinology · doi:10.1677/jme.1.02165 · Cited by 68
Aj, J., Mr, H., Anderson, J. T., Winter, W. E., & Peck, A. B. (1990) · PubMed · Cited by 61
Contribution of PAI-1 in cardiovascular pathology.
Alessi, M., & Juhan-Vague, I. (2004) · PubMed · Cited by 55
Tortoriello, D. V., McMinn, J. E., & Chua, S. C. (2006) · International Journal of Obesity · doi:10.1038/sj.ijo.0803392 · Cited by 51
Self-citationConfronting the Epidemic: The Need for Global Solutions
Rigby, N. J., Kumanyika, S., & James, W. P. T. (2004) · Journal of Public Health Policy · doi:10.1057/palgrave.jphp.3190040 · Cited by 49
Chronic in vivo hypoxia in various organs: Hypoxia-inducible factor-1α and apoptosis
Bianciardi, P., Fantacci, M., Caretti, A., Ronchi, R., Milano, G., Morel, S., von Segesser, L., Corno, A. F., & Samaja, M. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.02.042 · Cited by 45
Urano, M., Chen, Y., Humm, J. L., Koutcher, J. A., ZANZONICO, P. B., & Ling, C. C. (2002) · Radiation Research · doi:10.1667/0033-7587(2002)158[0167:mottot]2.0.co;2 · Cited by 35
Wen, B., Urano, M., O’Donoghue, J. A., & Ling, C. (2006) · Radiation Research · doi:10.1667/rr3602.1 · Cited by 19
Zhou, J.-T., Cai, Z., Li, N.-C., & Na, Y.-Q. (2006) · PubMed · Cited by 12
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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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