The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Reduced Adipose Tissue Oxygenation in Human Obesity
Open accessAbstract
OBJECTIVE— Based on rodent studies, we examined the hypothesis that increased adipose tissue (AT) mass in obesity without an adequate support of vascularization might lead to hypoxia, macrophage infiltration, and inflammation. RESEARCH DESIGN AND METHODS— Oxygen partial pressure (AT pO2) and AT temperature in abdominal AT (9 lean and 12 overweight/obese men and women) was measured by direct insertion of a polarographic Clark electrode. Body composition was measured by dual-energy X-ray absorptiometry, and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Abdominal subcutaneous tissue was used for staining, quantitative RT-PCR, and chemokine secretion assay. RESULTS— AT pO2 was lower in overweight/obese subjects than lean subjects (47 ± 10.6 vs. 55 ± 9.1 mmHg); however, this level of pO2 did not activate the classic hypoxia targets (pyruvate dehydrogenase kinase and vascular endothelial growth factor [VEGF]). AT pO2 was negatively correlated with percent body fat (R = −0.50, P < 0.05). Compared with lean subjects, overweight/obese subjects had 44% lower capillary density and 58% lower VEGF, suggesting AT rarefaction (capillary drop out). This might be due to lower peroxisome proliferator–activated receptor γ1 and higher collagen VI mRNA expression, which correlated with AT pO2 (P < 0.05). Of clinical importance, AT pO2 negatively correlated with CD68 mRNA and macrophage inflammatory protein 1α secretion (R = −0.58, R = −0.79, P < 0.05), suggesting that lower AT pO2 could drive AT inflammation in obesity. CONCLUSIONS— Adipose tissue rarefaction might lie upstream of both low AT pO2 and inflammation in obesity. These results suggest novel approaches to treat the dysfunctional AT found in obesity.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“We observed a marked decrease in the proportion of capillary endothelial cells in eWAT specifically during HFD feeding, consistent with the previously documented capillary rarefaction and elevated hypoxia associated with adipose tissue expansion (Rosen and Spiegelman, 2014; Pasarica et al., 2009).”
From Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity (2025) · cites this paper as Pasarica et al., 2009
In the citing paper
“For example, VEGF is upregulated in AT of mice fed a HFD for three days, but there are reports of both enhanced and reduced VEGF expression in chronic obesity (3,13,43,44), suggesting that sprouting angiogenesis is activated early and may or may not persist.”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [13]
In the citing paper
“Immune cells, particularly monocytes, migrate to areas of hypoxia, where they differentiate into proinflammatory macrophages (13,14).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [13]
In the citing paper
“Long-term HFF results in abnormal regulation of VEGF-A expression; not only do the VEGF-A levels decrease in the AT of obese mice and humans (13), but there is also evidence that the presence of VEGF in obese mice can block the regulation of neovascularization and vessel normalization (83).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [13]
In the citing paper
“Similar to findings in mice, human studies have reported that VEGF expression is reduced in obese humans (13).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [13]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425
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
Inflammation and insulin resistance
Shoelson, S. E. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29069 · Cited by 4,769
Bustin, S. A. (2000) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0250169 · Cited by 3,844
Adipokines: inflammation and the pleiotropic role of white adipose tissue
Trayhurn, P., & Wood, I. S. (2004) · British Journal of Nutrition · doi:10.1079/bjn20041213 · Cited by 2,210
Oxygen sensing by HIF hydroxylases
Schofield, C. J., & Ratcliffe, P. J. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1366 · Cited by 2,068
Adipose Tissue Hypoxia in Obesity and Its Impact on Adipocytokine Dysregulation
Hosogai, N., Fukuhara, A., Oshima, K., Miyata, Y., Tanaka, S., Segawa, K., Furukawa, S., Tochino, Y., Komuro, R., Matsuda, M., et al. (2007) · Diabetes · doi:10.2337/db06-0911 · Cited by 1,257 · cited 3×
“PDK1 are upregulated in adipocytes cultured in 1% oxygen (a hypoxic environment) (6,9,11).”
BackgroundMurdoch, C., Giannoudis, A., & Lewis, C. E. (2004) · Blood · doi:10.1182/blood-2004-03-1109 · Cited by 943
Adipose tissue mass can be regulated through the vasculature
Rupnick, M. A., Panigrahy, D., Zhang, C.-Y., Dallabrida, S. M., Lowell, B. B., Langer, R., & Folkman, M. J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162349799 · Cited by 845
Ye, J., Gao, Z., Yin, J., & He, Q. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00435.2007 · Cited by 840
Weyer, C., Foley, J. E., Bogardus, C., Tataranni, P. A., & Pratley, R. E. (2000) · Diabetologia · doi:10.1007/s001250051560 · Cited by 799
Failure of adipocyte differentiation causes type II diabetes mellitus?
Danforth, E. (2000) · Nature Genetics · doi:10.1038/79111 · Cited by 487
Pioglitazone Induces Mitochondrial Biogenesis in Human Subcutaneous Adipose Tissue In Vivo
Bogacka, I., Xie, H., Bray, G. A., & Smith, S. R. (2005) · Diabetes · doi:10.2337/diabetes.54.5.1392 · Cited by 467
Self-citationNishimura, S., Manabe, I., Nagasaki, M., Hosoya, Y., Yamashita, H., Fujita, H., Ohsugi, M., Tobe, K., Kadowaki, T., Nagai, R., et al. (2007) · Diabetes · doi:10.2337/db06-1749 · Cited by 440
Iyengar, P., Espina, V. A., Williams, T. W., Lin, Y., Berry, D. C., Jelicks, L. A., Lee, H., Temple, K. A., Graves, R., Pollard, J. W., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23424 · Cited by 429
Adipose tissue angiogenesis1,2
Hausman, G., & Richardson, R. L. (2004) · Journal of Animal Science · doi:10.2527/2004.823925x · Cited by 417
Wang, B., Wood, I. S., & Trayhurn, P. (2007) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-007-0301-8 · Cited by 392
Oxygen, a source of life and stress
Brahimi-Horn, M. C., & Pouysségur, J. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.06.018 · Cited by 383
Obesity Decreases Perioperative Tissue Oxygenation
Kabon, B., Nagele, A., Reddy, D., Eagon, C., Fleshman, J. W., Sessler, D. I., & Kurz, A. (2004) · Anesthesiology · doi:10.1097/00000542-200402000-00015 · Cited by 376
Paracrine Regulation of Angiogenesis and Adipocyte Differentiation During In Vivo Adipogenesis
Fukumura, D., Ushiyama, A., Duda, D. G., Xu, L., Tam, J., Krishna, V., Chatterjee, K., Garkavtsev, I., & Jain, R. K. (2003) · Circulation Research · doi:10.1161/01.res.0000099243.20096.fa · Cited by 365
Huber, J., Kiefer, F. W., Zeyda, M., Ludvik, B. H., Silberhumer, G. R., Prager, G., Zlabinger, G. J., & Stulnig, T. M. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2630 · Cited by 365
Di Gregorio, G. B., Yao-Borengasser, A., Rasouli, N., Varma, V., Lu, T., Miles, L. M., Ranganathan, G., Peterson, C. A., McGehee, R. E., & Kern, P. A. (2005) · Diabetes · doi:10.2337/diabetes.54.8.2305 · Cited by 362
Chemokines control fat accumulation and leptin secretion by cultured human adipocytes
Gerhardt, C. C., Romero, I. A., Cancello, R., Camoin, L., & Strosberg, A. D. (2001) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(01)00394-x · Cited by 352
Angiogenic Role of LYVE-1–Positive Macrophages in Adipose Tissue
Cho, C.-H., Jun Koh, Y., Han, J., Sung, H.-K., Jong Lee, H., Morisada, T., Schwendener, R. A., Brekken, R. A., Kang, G., Oike, Y., et al. (2007) · Circulation Research · doi:10.1161/01.res.0000259564.92792.93 · Cited by 309
Hypoxia Causes Glucose Intolerance in Humans
Oltmanns, K. M., Gehring, H., Rudolf, S., Schultes, B., Rook, S., Schweiger, U., Jan Born, A., Fehm, H. L., & Peters, A. (2004) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200308-1200oc · Cited by 217
Ukropcova, B., McNeil, M., Sereda, O., de Jonge, L., Xie, H., Bray, G. A., & Smith, S. R. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24332 · Cited by 213
Self-citationIncreased incidence of nosocomial infections in obese surgical patients.
Choban, P. S., Heckler, R., Burge, J. C., & Flancbaum, L. (1995) · PubMed · Cited by 204
Bogacka, I., Xie, H., Bray, G. A., & Smith, S. R. (2004) · Diabetes Care · doi:10.2337/diacare.27.7.1660 · Cited by 197
Self-citationGlycerol production in subcutaneous adipose tissue in lean and obese humans.
Jansson, P., Larsson, A., Smith, U., & Lönnroth, P. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115756 · Cited by 196
A Promoter Genotype and Oxidative Stress Potentially Link Resistin to Human Insulin Resistance
Smith, S. R., Bai, F., Charbonneau, C., Rossmeislová, L., & Argyropoulos, G. A. (2003) · Diabetes · doi:10.2337/diabetes.52.7.1611 · Cited by 188
Self-citationHuber, J., Löffler, M. G., Bilban, M., Reimers, M., Kadl, A., Todoric, J., Zeyda, M., Geyeregger, R., Schreiner, M., Weichhart, T., et al. (2006) · International Journal of Obesity · doi:10.1038/sj.ijo.0803511 · Cited by 154
Cloning of cell-specific secreted and surface proteins by subtractive antibody screening
Scherer, P. E., Bickel, P. E., Kotler, M., & Lodish, H. F. (1998) · Nature Biotechnology · doi:10.1038/nbt0698-581 · Cited by 144
Yamakawa, K., Hosoi, M., Koyama, H., Tanaka, S., Fukumoto, S., Morii, H., & Nishizawà, Y. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2665 · Cited by 136
Heat Production and Body Temperature During Cooling and Rewarming in Overweight and Lean Men
van Ooijen, A. M. J., Westerterp, K. R., Wouters, L., Schoffelen, P. F. M., van Steenhoven, A. A., & Lichtenbelt, W. D. V. M. (2006) · Obesity · doi:10.1038/oby.2006.223 · Cited by 119
Biscetti, F., Gaetani, E., Flex, A., Aprahamian, T. R., Hopkins, T. A., Straface, G., Pecorini, G., Stigliano, E., Smith, R. C., Angelini, F., et al. (2008) · Diabetes · doi:10.2337/db07-0765 · Cited by 115
Tissue Oxygenation in Obese and Non-obese Patients During Laparoscopy
Fleischmann, E., Kurz, A. M., Niedermayr, M., Schebesta, K., Kimberger, O., Sessler, D. I., Kabon, B., & Prager, G. (2005) · Obesity Surgery · doi:10.1381/0960892054222867 · Cited by 112
Impaired Adipose Tissue Development in Mice With Inactivation of Placental Growth Factor Function
LIJNEN, H. R., Christiaens, V., Scroyen, I., Vörös, G., Tjwa, M., Carmeliet, P., & Collen, D. (2006) · Diabetes · doi:10.2337/db06-0526 · Cited by 100
Adipose tissue growth and regression are regulated by angiopoietin-1
Dallabrida, S. M., Zurakowski, D., Shih, S., Smith, L. E. H., Folkman, J., Moulton, K. S., & Rupnick, M. A. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.10.007 · Cited by 88
Matsumoto, S., Morikawa, K., & Yanagida, M. (1981) · Journal of Molecular Biology · doi:10.1016/0022-2836(81)90255-2 · Cited by 83
Sotiropoulos, K. B., Clermont, A. C., Yasuda, Y., Rask‐Madsen, C., Mastumoto, M., Takahashi, J., Vecchia, K. M. D., Kondo, T., Aiello, L. P., & King, G. L. (2006) · The FASEB Journal · doi:10.1096/fj.05-4617fje · Cited by 81
Agouti Expression in Human Adipose Tissue
Smith, S. R., Gawrońska‐Kozak, B., Rossmeislová, L., Nguyen, T. M., Murrell, A., Stephens, J. M., & Mynatt, R. L. (2003) · Diabetes · doi:10.2337/diabetes.52.12.2914 · Cited by 72
Self-citationRegulation of the leptin content of obese human adipose tissue
Russell, C. D., Ricci, M. R., Brolin, R. E., Magill, E., & Fried, S. K. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.3.e399 · Cited by 52
Jakobsson, P., & Jorfeldt, L. (2006) · Clinical Physiology and Functional Imaging · doi:10.1111/j.1475-097x.2006.00686.x · Cited by 30
Development of subcutaneous wound oxygen measurement in humans: Contributions of Thomas K. Hunt, MD
Hopf, H. W. (2003) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.2003.11606.x · Cited by 19
Hausman, G. (1989) · Journal of Animal Science · doi:10.2527/jas1989.6751375x · Cited by 8
Flagged first, then by citations
Research works printed but not linked: 1
- Smith SR, Ravussin E: Role of Adipocyte in Metabolism and Endocrine Function. DeGroot, Jameson, Endocrinology, Philadelphia, Elsevier Saunders, 2006
Cited by
Sorted by citations
The metabolic phenotype in obesity: Fat mass, body fat distribution, and adipose tissue function
Goossens, G. H. (2017) · Obesity Facts · doi:10.1159/000471488 · Cited by 8,481
Adipokines in inflammation and metabolic disease
Ouchi, N., Parker, J. L., Lugus, J. J., & Walsh, K. (2011) · Nature Reviews Immunology · doi:10.1038/nri2921 · Cited by 4,625
Type 2 diabetes as an inflammatory disease
Donath, M. Y., & Shoelson, S. E. (2011) · Nature Reviews Immunology · doi:10.1038/nri2925 · Cited by 3,737
Inflammation in obesity, diabetes, and related disorders
Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.013 · Cited by 2,066
Adipose tissue inflammation and metabolic dysfunction in obesity
Kawai, T., Autieri, M. V., & Scalia, R. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00379.2020 · Cited by 1,947
Metadata
- Authors
- Pasarica, M., Sereda, O. R., Redman, L. M., Albarado, D. C., Hymel, D. T., Roan, L. E., Rood, J. C., Burk, D. H., & Smith, S. R.
- Affiliations
- Pennington Biomedical Research Center (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2009-03-01
- Volume
- 58
- Issue
- 3
- Pages
- 718-725
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2646071
- OpenAlex
- W2171965603
- Cited by
- 786
- References
- 46
- Citations by year
- 2026: 27 · 2025: 25 · 2024: 40 · 2023: 32 · 2022: 47 · 2021: 41 · 2020: 48 · 2019: 58 · 2018: 54 · 2017: 56 · 2016: 39 · 2015: 53 · 2014: 53 · 2013: 66 · 2012: 46
- FWCI
- 25.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Civil War Book Review (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK072476, P30DK072476)
- 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
- adipose tissue hypoxia, obesity, adipose tissue inflammation, macrophage infiltration, capillary density, vascular endothelial growth factor, PPARγ, collagen VI, CD68, macrophage inflammatory protein-1alpha, insulin sensitivity, adipose tissue vascularization
- MeSH terms
- Abdomen, Adipose Tissue, Hypoxia, Blood Pressure, Body Composition, Body Temperature, Female, Humans, Hyperinsulinism, Inflammation, Male, Obesity, Organ Size, Oxygen, Partial Pressure, Reference Values, Glucose Clamp Technique, Absorptiometry, Photon, Patient Selection, Reverse Transcriptase Polymerase Chain Reaction, Overweight
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review