Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity?
Open accessAbstract
White adipose tissue is a key endocrine and secretory organ, releasing multiple adipokines, many of which are linked to inflammation and immunity. During the expansion of adipose tissue mass in obesity there is a major inflammatory response in the tissue with increased expression and release of inflammation-related adipokines, including IL-6, leptin, monocyte chemoattractant protein-1 and TNF-α, together with decreased adiponectin production. We proposed in 2004 (Trayhurn & Wood,Br J Nutr92, 347–355) that inflammation in adipose tissue in obesity is a response to hypoxia in enlarged adipocytes distant from the vasculature. Hypoxia has now been directly demonstrated in adipose tissue of several obese mouse models (ob/ob, KKAy, diet-induced) and molecular studies indicate that the level of the hypoxia-inducible transcription factor, hypoxia-inducible factor-1α, is increased, as is expression of the hypoxia-sensitive marker gene, GLUT1. Cell- culture studies on murine and human adipocytes show that hypoxia (induced by low O 2 or chemically) leads to stimulation of the expression and secretion of a number of inflammation-related adipokines, including angiopoietin-like protein 4, IL-6, leptin, macrophage migration inhibitory factor and vascular endothelial growth factor. Hypoxia also stimulates the inflammatory response of macrophages and inhibits adipocyte differentiation from preadipocytes. GLUT1 gene expression, protein level and glucose transport by human adipocytes are markedly increased by hypoxia, indicating that low O 2 tension stimulates glucose utilisation. It is suggested that hypoxia has a pervasive effect on adipocyte metabolism and on overall adipose tissue function, underpinning the inflammatory response in the tissue in obesity and the subsequent development of obesity-associated diseases, particularly type 2 diabetes and the metabolic syndrome.
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The enlargement of adipose tissue in obesity induces mechanical stress, ER stress and hypoxia in adipocytes, resulting in the release of free fatty acids and inflammatory cytokines such as IL-6 and TNFα and chemokines, suggesting activation of the IL-6 Amp.
“The enlargement of adipose tissue in obesity induces mechanical stress, ER stress and hypoxia in adipocytes, resulting in the release of free fatty acids (FFAs) and inflammatory cytokines such as IL-6 and TNFα and chemokines (303–305), suggesting activation of the IL-6 Amp.”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [305]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredGalectin-3 ablation accelerates lipid-induced atherogenesis.
“and recent studies have shown that galectin-3 ablation accelerates lipid-induced atherogenesis (501) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [501]
Hypoxia in adipose tissue of obese patients is supported by the observation that cardiac output and blood flow directed to adipose tissue are not increased during obesity.
“In humans, the existence of hypoxia in the adipose tissue of obese patients is supported by the observation that although obese patients have more adipose tissue than lean patients, the cardiac output and blood flow directed to adipose tissue are not increased during obesity (24).”
From Hypoxia decreases insulin signaling pathways in adipocytes. (2009) · cites this paper as [24]
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Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419 · see citing works
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 · see citing works
Inflammation and metabolic disorders
Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199 · see citing works
Adipose 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 · see citing works
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 · see citing works
Targeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717 · see citing works
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535 · see citing works
Adipose Tissue as an Endocrine Organ
Kershaw, E. E., & Flier, J. S. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0395 · Cited by 5,522 · see citing works
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001) · Nature Medicine · doi:10.1038/90984 · Cited by 4,915 · see citing works
Paradoxical Decrease of an Adipose-Specific Protein, Adiponectin, in Obesity
Arita, Y., Kihara, S., Ouchi, N., Takahashi, M., Maeda, K., Miyagawa, J.-I., Hotta, K., Shimomura, I., Nakamura, T., Miyaoka, K., et al. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0255 · Cited by 4,856 · see citing works
Why Do Cancers Have High Aerobic Glycolysis?
Gatenby, R. A., & Gillies, R. J. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1478 · Cited by 4,784 · see citing works
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735 · see citing works
Inflammation, stress, and diabetes
Wellen, K. E., & Hotamisligil, G. S. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25102 · Cited by 4,143 · see citing works
Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
Özcan, U., Cao, Q., Yilmaz, E., Lee, A.-H., Iwakoshi, N. N., Özdelen, E., Tuncman, G., Görgün, C., Glimcher, L. H., & Hotamisligil, G. S. (2004) · Science · doi:10.1126/science.1103160 · Cited by 3,844 · see citing works
The adipocyte-secreted protein Acrp30 enhances hepatic insulin action
Berg, A. H., Combs, T. P., Du, X., Brownlee, M., & Scherer, P. E. (2001) · Nature Medicine · doi:10.1038/90992 · Cited by 2,526 · see citing works
Reactive oxygen species have a causal role in multiple forms of insulin resistance
Houstis, N., Rosen, E. D., & Lander, E. S. (2006) · Nature · doi:10.1038/nature04634 · Cited by 2,525 · see citing works
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 · see citing works
Self-citationAdipocytes as regulators of energy balance and glucose homeostasis
Rosen, E. D., & Spiegelman, B. M. (2006) · Nature · doi:10.1038/nature05483 · Cited by 2,170 · cited 1× · see citing works
“This state of inflammation, particularly in adipose tissue through changes in the release of inflammation-related adipokines and the infiltration of macrophages((13,14)), is viewed as central to the development of the major obesity-associated diseases – the metabolic syndrome, type 2 diabetes, CVD and certain cancers…”
Novel Modulator for Endothelial Adhesion Molecules
Ouchi, N., Kihara, S., Arita, Y., Maeda, K., Kuriyama, H., Okamoto, Y., Hotta, K., Nishida, M., Takahashi, M., Nakamura, T., et al. (1999) · Circulation · doi:10.1161/01.cir.100.25.2473 · Cited by 2,139 · see citing works
Ouchi, N., Kihara, S., Arita, Y., Okamoto, Y., Maeda, K., Kuriyama, H., Hotta, K., Nishida, M., Takahashi, M., Muraguchi, M., et al. (2000) · Circulation · doi:10.1161/01.cir.102.11.1296 · Cited by 1,730 · see citing works
Fain, J. N., Madan, A. K., Hiler, M. L., Cheema, P. S., & Bahouth, S. W. (2004) · Endocrinology · doi:10.1210/en.2003-1336 · Cited by 1,571 · see citing works
Sequence and Structure of a Human Glucose Transporter
Mueckler, M. M., Caruso, C., Baldwin, S. A., Panico, M., Blench, I., Morris, H. R., Allard, W. J., Lienhard, G. E., & Lodish, H. F. (1985) · Science · doi:10.1126/science.3839598 · Cited by 1,529 · see citing works
Biological Action of Leptin as an Angiogenic Factor
Sierra-Honigmann, M. R., Nath, A. K., Murakami, C., García‐Cardeña, G., Papapetropoulos, A., Sessa, W. C., Madge, L. A., Schechner, J. S., Schwabb, M. B., Polverini, P. J., et al. (1998) · Science · doi:10.1126/science.281.5383.1683 · Cited by 1,371 · see citing works
Relationship between Adipocyte Size and Adipokine Expression and Secretion
Skurk, T., Alberti-Huber, C., Herder, C., & Hauner, H. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1055 · Cited by 1,288 · see citing works
HIF-1 and mechanisms of hypoxia sensing
Semenza, G. L. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00194-0 · Cited by 1,267 · see citing works
Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ
Trayhurn, P., & Beattie, J. H. (2001) · Proceedings of The Nutrition Society · doi:10.1079/pns200194 · Cited by 1,259 · see citing works
Self-citationAdipose 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 20× · see citing works
“This has been directly examined recently in the context of macrophage involvement in adipose tissue function, with the induction of IL-1 b , IL-6, MIF, TNF-a and VEGF gene expression under hypoxia being evident in peritoneal macrophages (40) .”
InfluentialMinireview: The Adipocyte—At the Crossroads of Energy Homeostasis, Inflammation, and Atherosclerosis
Rajala, M. W., & Scherer, P. E. (2003) · Endocrinology · doi:10.1210/en.2003-0580 · Cited by 1,190 · see citing works
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 · see citing works
Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins
Wood, I. S., & Trayhurn, P. (2003) · British Journal of Nutrition · doi:10.1079/bjn2002763 · Cited by 889 · see citing works
Self-citationYe, J., Gao, Z., Yin, J., & He, Q. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00435.2007 · Cited by 840 · see citing works
Leptin, the Product of Ob Gene, Promotes Angiogenesis
Bouloumié, A., Drexler, H. C. A., Lafontan, M., & Busse, R. (1998) · Circulation Research · doi:10.1161/01.res.83.10.1059 · Cited by 715 · see citing works
Koumenis, C., Naczki, C., Koritzinsky, M., Rastani, S., Diehl, J. A., Sonenberg, N., Koromilas, A. E., & Wouters, B. G. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.21.7405-7416.2002 · Cited by 688 · see citing works
Fain, J. N. (2006) · Vitamins and hormones · doi:10.1016/s0083-6729(06)74018-3 · Cited by 679 · see citing works
Tissue oxygen tension and brain sensitivity to hypoxia
Erecińska, M., & Silver, I. A. (2001) · Respiration Physiology · doi:10.1016/s0034-5687(01)00306-1 · Cited by 615 · see citing works
Gregor, M. F., & Hotamisligil, G. S. (2007) · Journal of Lipid Research · doi:10.1194/jlr.r700007-jlr200 · Cited by 586 · see citing works
Rausch, M. E., Weisberg, S., Vardhana, P., & Tortoriello, D. V. (2008) · International Journal of Obesity · doi:10.1038/sj.ijo.0803744 · Cited by 585 · see citing works
Hypoxia-responsive transcription factors
Cummins, E. P., & Taylor, C. T. (2005) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-005-1413-7 · Cited by 462 · see citing works
Inhibition of PPARγ2 Gene Expression by the HIF-1-Regulated Gene DEC1/Stra13
Yun, Z., Maecker, H. L., Johnson, R. S., & Giaccia, A. J. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00131-4 · Cited by 460 · see citing works
Adipsin: A Circulating Serine Protease Homolog Secreted by Adipose Tissue and Sciatic Nerve
Cook, K. S., Min, H. Y., Johnson, D., Chaplinsky, R. J., Flier, J. S., Hunt, C. R., & Spiegelman, B. M. (1987) · Science · doi:10.1126/science.3299705 · Cited by 427 · see citing works
Wang, B., Wood, I. S., & Trayhurn, P. (2007) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-007-0301-8 · Cited by 392 · see citing works
Self-citationMacrophage responses to hypoxia: relevance to disease mechanisms
Lewis, J. S., Lee, J. A., Underwood, J. C. E., Harris, A. L., & Lewis, C. E. (1999) · Journal of Leukocyte Biology · doi:10.1002/jlb.66.6.889 · Cited by 383 · see citing works
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 · see citing works
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 · see citing works
Intermittent Hypoxia Increases Insulin Resistance in Genetically Obese Mice
Polotsky, V. Y., Li, J., Punjabi, N. M., Rubin, A. E., Smith, P. L., Schwartz, A. R., & O'Donnell, C. P. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.048173 · Cited by 375 · see citing works
Intermittent Hypoxia Causes Insulin Resistance in Lean Mice Independent of Autonomic Activity
Iiyori, N., Alonso, L. C., Li, J., Sanders, M. H., Garcia-Ocana, A., O'Doherty, R. M., Polotsky, V. Y., & O'Donnell, C. P. (2007) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200610-1527oc · Cited by 373 · see citing works
Retinal degeneration and local oxygen metabolism
Yu, D., & Cringle, S. J. (2005) · Experimental Eye Research · doi:10.1016/j.exer.2005.01.018 · Cited by 367 · see citing works
Zhang, Q.-X., Magovern, C. J., Mack, C. A., Budenbender, K. T., Ko, W., & Rosengart, T. K. (1997) · Journal of Surgical Research · doi:10.1006/jsre.1996.4983 · Cited by 365 · see citing works
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 344 · see citing works
Jan, S. L., Amy, C., Cazes, A., Monnot, C., Lamandé, N., Favier, J., Philippe, J., Sibony, M., Gasc, J., Corvol, P. L., et al. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64285-x · Cited by 342 · see citing works
Severely Impaired Adipsin Expression in Genetic and Acquired Obesity
Flier, J. S., Cook, K. S., Usher, P., & Spiegelman, B. M. (1987) · Science · doi:10.1126/science.3299706 · Cited by 329 · see citing works
A role for preadipocytes as macrophage‐like cells
Cousin, B., Muñoz, O., André, M., Fontanilles, A. M., Dani, C., Cousin, J. L., Laharrague, P. F., Casteilla, L., & Pénicaud, L. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.2.305 · Cited by 320 · see citing works
Virtanen, K. A., Lönnroth, P., Parkkola, R., Peltoniemi, P., Asola, M., Viljanen, T., Tolvanen, T., Knuuti, J., Rönnemaa, T., Huupponen, R., et al. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.87.8.3902 · Cited by 315 · see citing works
Adipose tissue, insulin action and vascular disease: inflammatory signals
Yudkin, J. S. (2003) · International Journal of Obesity · doi:10.1038/sj.ijo.0802496 · Cited by 311 · cited 1× · see citing works
“…through changes in the release of inflammation-related adipokines and the infiltration of macrophages (13,14) , is viewed as central to the development of the major obesity-associated diseases – the metabolic syndrome, type 2 diabetes, CVD and certain cancers (such as breast and colon) (5,10,15) .”
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 · see citing works
Expression of ob Gene in Adipose Cells
Leroy, P., Dessolin, S., Villageois, P., Moon, B. C., Friedman, J. M., Ailhaud, G. P., & Dani, C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.5.2365 · Cited by 280 · see citing works
Faßhauer, M., Klein, J. C., Neumann, S., Eszlinger, M., & Paschke, R. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02960-x · Cited by 263 · see citing works
Chung, S., LaPoint, K., Martinez, K., Kennedy, A. J., Sandberg, M. B., & McIntosh, M. (2006) · Endocrinology · doi:10.1210/en.2006-0536 · Cited by 252 · see citing works
Chen, B., Lam, K. S. L., Wang, Y., Wu, D., Lam, M. C., Shen, J., Wong, L., Hoo, R. L. C., Zhang, J., & Xu, A. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.01.004 · Cited by 238 · see citing works
Wang, B., Jenkins, J. R., & Trayhurn, P. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00475.2004 · Cited by 233 · see citing works
Self-citationEffects of hypoxia on the expression of proangiogenic factors in differentiated 3T3-F442A adipocytes
Lolmède, K., Durand de Saint Front, V, Galitzky, J., Lafontan, M., & Bouloumié, A. (2003) · International Journal of Obesity · doi:10.1038/sj.ijo.0802407 · Cited by 224 · see citing works
Carrière, A., Carmona, M.-C., Fernandez, Y., Rigoulet, M., Wenger, R. H., Pénicaud, L., & Casteilla, L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407258200 · Cited by 220 · see citing works
Gene regulation under low oxygen: holding your breath for transcription
Rocha, S. (2007) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2007.06.005 · Cited by 219 · see citing works
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 215 · see citing works
The effect of altitude hypoxia on glucose homeostasis in men
Larsen, J. J., Hansen, J. M., Olsen, N. V., Galbo, H., & Dela, F. (1997) · The Journal of Physiology · doi:10.1111/j.1469-7793.1997.241bf.x · Cited by 205 · see citing works
Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions
Ren, H., Cao, Y., Zhao, Q., Li, J., Zhou, C.-X., Liao, L., Jia, M., Zhao, Q., Cai, H., Han, Z., et al. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.05.169 · Cited by 201 · see citing works
Differentiation Arrest by Hypoxia
Lin, Q., Lee, Y., & Yun, Z. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.c600120200 · Cited by 200 · see citing works
Cancer: looking outside the genome
Folkman, J., Hahnfeldt, P., & Hlatky, L. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35036100 · Cited by 191 · see citing works
HIFs and tumors—causes and consequences
Höpfl, G., Ogunshola, O. O., & Gassmann, M. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00538.2003 · Cited by 185 · see citing works
Karpe, F., Fielding, B. A., Ilic, V., Macdonald, I. A., Summers, L. K. M., & Frayn, K. N. (2002) · Diabetes · doi:10.2337/diabetes.51.8.2467 · Cited by 177 · see citing works
Regional blood flow in genetically obese (ob/ob) mice
Thurlby, P. L., & Trayhurn, P. (1980) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00647457 · Cited by 176 · see citing works
Self-citationHypoxia inducible factor regulates the cardiac expression and secretion of apelin
Ronkainen, V., Ronkainen, J. J., Hänninen, S. L., Leskinen, H. K., Ruas, J. L., Pereira, T., Poellinger, L., Vuolteenaho, O. J., & Tavi, P. (2007) · The FASEB Journal · doi:10.1096/fj.06-7294com · Cited by 169 · see citing works
Claycombe, K., Harkins, J. M., Chung, Y.-J., Penner, K. M., Pestka, J. J., North, C. M., & Moustaïd‐Moussa, N. (2004) · Journal of Nutrition · doi:10.1093/jn/134.10.2673 · Cited by 169 · see citing works
Production and Release of Macrophage Migration Inhibitory Factor from Human Adipocytes
Skurk, T., Herder, C., Kräft, I., Müller-Scholze, S., Hauner, H., & Kolb, H. (2004) · Endocrinology · doi:10.1210/en.2004-0924 · Cited by 151 · see citing works
Wood, I. S., Wang, B., Lorente‐Cebrián, S., & Trayhurn, P. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.07.032 · Cited by 143 · see citing works
Self-citationHypoxic induction of human visfatin gene is directly mediated by hypoxia‐inducible factor‐1
Bae, S., Kim, S.-R., Kim, J. G., Kim, J. Y., Koo, T. H., Jang, H., Yun, I., Yoo, M., & Bae, M. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.06.052 · Cited by 125 · see citing works
Activation of hypoxia-inducible factor 1 during macrophage differentiation
Oda, T., Hirota, K., Nishi, K., Takabuchi, S., Oda, S., Yamada, H., Arai, T., Fukuda, K., Kita, T., Adachi, T., et al. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00614.2005 · Cited by 124 · see citing works
HIF-1 regulates hypoxia- and insulin-induced expression of apelin in adipocytes
Glassford, A. J., Yue, P., Sheikh, A. Y., Chun, H. J., Zarafshar, S., Chan, D. A., Reaven, G. M., Quertermous, T., & Tsao, P. S. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00490.2007 · Cited by 121 · see citing works
Regulation of leptin production: a dominant role for the sympathetic nervous system?
Trayhum, P., Duncan, J. S., Hoggard, N., & Rayner, D. V. (1998) · Proceedings of The Nutrition Society · doi:10.1079/pns19980060 · Cited by 113 · see citing works
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 · see citing works
Regulation of oxygen sensing by ion channels
López-Barneo, J., del Toro, R., Levitsky, K. L., Chiara, M. D., & Ortega-Sáenz, P. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00929.2003 · Cited by 106 · see citing works
Visfatin in adipocytes is upregulated by hypoxia through HIF1α-dependent mechanism
Segawa, K., Fukuhara, A., Hosogai, N., Morita, K., Okuno, Y., Tanaka, M., Nakagawa, Y., Kihara, S., Funahashi, T., Komuro, R., et al. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.07.083 · Cited by 99 · see citing works
Zhou, S., Lechpammer, S., Greenberger, J. S., & Glowacki, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412953200 · Cited by 96 · see citing works
Gulve, E. A., Ren, J., Marshall, B. A., Gao, J., Hansen, P. A., Holloszy, J. O., & Mueckler, M. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32316-5 · Cited by 93 · see citing works
Hypoxia Selectively Inhibits Monocyte Chemoattractant Protein-1 Production by Macrophages
Bosco, M. C., Puppo, M., Pastorino, S., Mi, Z., Melillo, G., Massazza, S., Rapisarda, A., & Varesio, L. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.3.1681 · Cited by 93 · see citing works
Hypoxia inhibits adipocyte differentiation in a HDAC-independent manner
Kim, K. H., Song, M. J., Chung, J., Park, H., & Kim, J. B. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.06.023 · Cited by 83 · see citing works
Relationship of adipose tissue blood flow to fat cell size and number
GIROLAMO, M. D., Skinner, N. S., Hanley, H. G., & Sachs, R. H. (1971) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1971.220.4.932 · Cited by 79 · see citing works
PCR arrays identify metallothionein-3 as a highly hypoxia-inducible gene in human adipocytes
Wang, B., Wood, I. S., & Trayhurn, P. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.01.036 · Cited by 77 · see citing works
Self-citationAdipocyte blood flow is decreased in obese Zucker rats
West, D. B., Prinz, W. A., Francendese, A. A., & Greenwood, M. R. (1987) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1987.253.2.r228 · Cited by 65 · see citing works
Wood, I. S., Hunter, L., & Trayhurn, P. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01322-6 · Cited by 60 · see citing works
Self-citationMetallothionein Gene Expression in Human Adipose Tissue from Lean and Obese Subjects
Do, M., Nam, S.-Y., Hong, S., Kim, K. W., Duncan, J. S., Beattie, J. H., & Trayhurn, P. (2002) · Hormone and Metabolic Research · doi:10.1055/s-2002-33254 · Cited by 36 · see citing works
Self-citationExpression of metallothionein-III induced by hypoxia attenuates hypoxia-induced cell death in vitro
Tanji, K., Irie, Y., Uchida, Y., Mori, F., Satoh, K., Mizushima, Y., & Wakabayashi, K. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02633-7 · Cited by 30 · see citing works
[Cloning of a novel gene, ANGPTL4 and the functional study in angiogenesis].
Zhu, H., Li, J., Qin, W., et al. (2002) · PubMed · Cited by 21 · see citing works
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IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453 · see citing works
“The enlargement of adipose tissue in obesity induces mechanical stress, ER stress and hypoxia in adipocytes, resulting in the release of free fatty acids (FFAs) and inflammatory cytokines such as IL-6 and TNF α and chemokines (303–305), suggesting activation of the IL-6 Amp.”
BackgroundAdapting to obesity with adipose tissue inflammation
Reilly, S. M., & Saltiel, A. R. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.90 · Cited by 1,204 · see citing works
Dietary factors and low-grade inflammation in relation to overweight and obesity
Calder, P. C., Ahluwalia, N., Brouns, F., Buetler, T., Clement, K., Cunningham, K., Esposito, K., Jönsson, L. S., Kolb, H., Lansink, M., et al. (2011) · British Journal of Nutrition · doi:10.1017/s0007114511005460 · Cited by 1,098 · see citing works
Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome
Maury, E., & Brichard, S. M. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.07.031 · Cited by 1,026 · see citing works
Adipose tissue expandability, lipotoxicity and the Metabolic Syndrome — An allostatic perspective
Virtue, S., & Vidal-Puig, A. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.12.006 · Cited by 1,013 · see citing works
Klöting, N., Fasshauer, M., Dietrich, A., Kovacs, P., Schön, M. R., Kern, M., Stumvoll, M., & Blüher, M. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00586.2009 · Cited by 856 · see citing works
Obesity and related consequences to ageing
Jura, M., & Kozak, L. P. (2016) · AGE · doi:10.1007/s11357-016-9884-3 · Cited by 473 · see citing works
Transdifferentiation properties of adipocytes in the adipose organ
Cinti, S. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00183.2009 · Cited by 379 · see citing works
Gealekman, O., Guseva, N., Hartigan, C., Apotheker, S., Gorgoglione, M., Gurav, K., Tran, K.-V., Straubhaar, J., Nicoloro, S., Czech, M. P., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.970145 · Cited by 346 · see citing works
Hypoxia decreases insulin signaling pathways in adipocytes.
Regazzetti, C., Peraldi, P., Grémeaux, T., Najem-Lendom, R., Ben-Sahra, I., Cormont, M., Bost, F., Le Marchand-Brustel, Y., Tanti, J.-F., & Giorgetti-Peraldi, S. (2009) · Diabetes · doi:10.2337/db08-0457 · Cited by 281 · see citing works
The autocrine and paracrine roles of adipokines
Karastergiou, K., & Mohamed-Ali, V. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.11.011 · Cited by 233 · see citing works
Hypoxia and Adipocyte Physiology: Implications for Adipose Tissue Dysfunction in Obesity
Trayhurn, P. (2014) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071812-161156 · Cited by 194 · see citing works
Self-citationZhang, X., Lam, K. S. L., Ye, H., Chung, S. K., Zhou, M., Wang, Y., & Xu, A. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.135509 · Cited by 112 · see citing works
Matsuura, H., Ichiki, T., Inoue, E., Nomura, M., Miyazaki, R., Hashimoto, T., Ikeda, J., Takayanagi, R., Fong, G.-H., & Sunagawa, K. (2013) · Circulation · doi:10.1161/circulationaha.113.001742 · Cited by 77 · see citing works
Guglielmi, O., Lanteri, P., & Garbarino, S. (2019) · Sleep Medicine · doi:10.1016/j.sleep.2019.01.042 · Cited by 71 · see citing works
GLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunction
Pastel, E., McCulloch, L. J., Ward, R., Joshi, S., Gooding, K. M., Shore, A. C., & Kos, K. (2017) · Clinical Science · doi:10.1042/cs20160803 · Cited by 49 · see citing works
Rittweger, J., Debevec, T., Frings-Meuthen, P., Lau, P., Mittag, U., Ganse, B., Ferstl, P. G., Simpson, E. J., Macdonald, I. A., Eiken, O., et al. (2016) · Bone · doi:10.1016/j.bone.2016.07.013 · Cited by 35 · see citing works
Luo, X., Jia, R., Yao, Q., Xu, Y., Luo, Z., Luo, X., & Wang, N. (2016) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500714 · Cited by 30 · see citing works
- Authors
- Trayhurn, P., Wang, B., & Wood, I. S.
- Affiliations
- University of Liverpool (GB)
- Corresponding author
- Trayhurn, Paul
- Venue
- British Journal of Nutrition
- Publisher
- Cambridge University Press (CUP)
- Published
- 2008-08
- Volume
- 100
- Issue
- 2
- Pages
- 227-235
- ISSN
- 0007-1145 (ISSN-L)
- 1475-2662
- OpenAlex
- W1972235985
- Cited by
- 464
- References
- 93
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 14 · 2023: 21 · 2022: 27 · 2021: 11 · 2020: 16 · 2019: 18 · 2018: 22 · 2017: 25 · 2016: 23 · 2015: 24 · 2014: 25 · 2013: 45 · 2012: 32
- FWCI
- 5.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal Of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- hypoxia, white adipose tissue, obesity, adipose tissue inflammation, adipokines, hypoxia-inducible factor-1α, GLUT1, glucose transport, adipogenesis, macrophage inflammation, ANGPTL4, leptin, interleukin-6, adiponectin, type 2 diabetes, metabolic syndrome
- MeSH terms
- Adipose Tissue, Animals, Humans, Obesity, Signal Transduction, Cell Hypoxia, Adipocytes, Adipose Tissue, White, Adipokines
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.
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