Increased Adipocyte O2 Consumption Triggers HIF-1α, Causing Inflammation and Insulin Resistance in Obesity
Open accessAbstract
Adipose tissue hypoxia and inflammation have been causally implicated in obesity-induced insulin resistance. Here, we report that, early in the course of high-fat diet (HFD) feeding and obesity, adipocyte respiration becomes uncoupled, leading to increased oxygen consumption and a state of relative adipocyte hypoxia. These events are sufficient to trigger HIF-1α induction, setting off the chronic adipose tissue inflammatory response characteristic of obesity. At the molecular level, these events involve saturated fatty acid stimulation of the adenine nucleotide translocase 2 (ANT2), an inner mitochondrial membrane protein, which leads to the uncoupled respiratory state. Genetic or pharmacologic inhibition of either ANT2 or HIF-1α can prevent or reverse these pathophysiologic events, restoring a state of insulin sensitivity and glucose tolerance. These results reveal the sequential series of events in obesity-induced inflammation and insulin resistance.
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In insulin-responsive tissues, sustained HIF-1 activation promotes a shift toward glycolytic metabolism, alters mitochondrial function, and contributes to insulin resistance by disrupting normal oxidative metabolism and redox balance.
“In insulin responsive tissues, sustained HIF-1 activation promotes a shift toward glycolytic metabolism, alters mitochondrial function, and contributes to insulin resistance by disrupting normal oxidative metabolism and redox balance [236,237].”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [236]
The Results section (page unavailable) links adipocyte HIF-1α activation in high-fat-diet mice to increased lactate production and shows that adipocyte HIF-1α deletion changes oxygen consumption. The Discussion (page unavailable) links HIF-1α induction to inflammation and insulin resistance. The paper does not establish the claimed mechanism of disrupted redox balance, and its direct findings concern adipocytes rather than insulin-responsive tissues generally; it also places uncoupled mitochondrial respiration upstream of HIF-1α induction. (LLM, conf=0.85)
Experimental — accuracy not yet measuredAdipocytes respond to hypoxia by inducing glycolysis and angiogenesis.
“Adipocytes respond by inducing glycolysis and angiogenesis in an attempt to alleviate the hypoxia (3).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [3]
VEGF is upregulated in adipose tissue of mice fed a high-fat diet for three days, but reports in chronic obesity show both enhanced and reduced VEGF expression.
“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 [3]
HIF-2α attenuates high-fat-diet-induced inflammation.
“In contrast, HIF-2α attenuates HFD-induced inflammation (3).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [3]
Within three days of high-fat feeding, rapid adipocyte hypertrophy and mitochondrial uncoupling raise oxygen demand and lower oxygen availability.
“Within three days of HFF, rapid adipocyte hypertrophy along with mitochondrial uncoupling increase the demand for oxygen and reduce oxygen availability (3).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [3]
HIF-1α signaling dominates over HIF-2α in obesity and causally contributes to early adipose tissue dysfunction.
“Although HIF-1α and HIF-2α pathways can interact, HIF-1α signaling dominates in obesity, playing a causative role in early AT dysfunction (3).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [3]
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A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
Folch, J., Lees, M., & Stanley, G. H. S. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64849-5 · Cited by 65,189 · see citing works
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 · see citing works
Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients
Locatelli, F., Fishbane, S. N., Block, G. A., & Macdougall, I. C. (2017) · American Journal of Nephrology · doi:10.1159/000455166 · Cited by 4,834 · see citing works
HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression
Keith, B., Johnson, R. S., & Simon, M. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3183 · Cited by 1,693 · 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 1× · see citing works
“, 2009), and recent evidence suggests that this can cause adipose tissue dysfunction in obesity (Hosogai et al., 2007).”
Identification of a Lipokine, a Lipid Hormone Linking Adipose Tissue to Systemic Metabolism
Cao, H.-M., Gerhold, K., Mayers, J. R., Wiest, M., Watkins, S., & Hotamışlıgil, G. S. (2008) · Cell · doi:10.1016/j.cell.2008.07.048 · Cited by 1,142 · see citing works
Self-citationHe, W., Barak, Y., Hevener, A. L., Olson, P., Liao, D., Le, J., Nelson, M. C., Ong, E. S., Olefsky, J. M., & Evans, R. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2536828100 · Cited by 978 · see citing works
Self-citationInflammation and Lipid Signaling in the Etiology of Insulin Resistance
Glass, C. K., & Olefsky, J. M. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.001 · Cited by 942 · see citing works
Self-citationSplanchnic lipolysis in human obesity
Nielsen, S., Guo, Z., Johnson, C. M., Hensrud, D. D., & Jensen, M. D. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21047 · Cited by 933 · see citing works
Hypoxia-Inducible Factor 1α Induces Fibrosis and Insulin Resistance in White Adipose Tissue
Halberg, N., Khan, T., Trujillo, M. E., Wernstedt-Asterholm, I., Attie, A. D., Sherwani, S., Wang, Z. V., Landskroner-Eiger, S., Dineen, S., Magalang, U. J., et al. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00192-09 · Cited by 896 · see citing works
Reduced Adipose Tissue Oxygenation in Human Obesity
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. (2009) · Diabetes · doi:10.2337/db08-1098 · Cited by 786 · see citing works
Redistribution of Intracellular Oxygen in Hypoxia by Nitric Oxide: Effect on HIF1α
Hagen, T., Taylor, C. T., Lam, F., & Moncada, S. (2003) · Science · doi:10.1126/science.1088805 · Cited by 704 · see citing works
Takeda, N., O'Dea, E. L., Doedens, A. L., Kim, J., Weidemann, A., Stockmann, C., Asagiri, M., Simon, M. C., Hoffmann, A., & Johnson, R. S. (2010) · Genes & Development · doi:10.1101/gad.1881410 · Cited by 621 · see citing works
Self-citationA Stress Signaling Pathway in Adipose Tissue Regulates Hepatic Insulin Resistance
Sabio, G., Das, M., Mora, A., Zhang, Z., Jun, J. Y., Ko, H. J., Barrett, T., Kim, J. K., & Davis, R. J. (2008) · Science · doi:10.1126/science.1160794 · Cited by 604 · see citing works
Self-citationBarak, Y., Liao, D., He, W., Ong, E. S., Nelson, M. C., Olefsky, J. M., Boland, R., & Evans, R. M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012610299 · Cited by 586 · see citing works
Self-citationInflammation Is Necessary for Long-Term but Not Short-Term High-Fat Diet–Induced Insulin Resistance
Lee, Y. S., Li, P., Huh, J. Y., Hwang, I. J., Lu, M., Kim, J. I., Ham, M., Talukdar, S., Chen, A., Lu, W. J., et al. (2011) · Diabetes · doi:10.2337/db11-0194 · Cited by 566 · see citing works
Self-citationPerreault, M., & Marette, A. (2001) · Nature Medicine · doi:10.1038/nm1001-1138 · Cited by 540 · see citing works
Desnutrin/ATGL Is Regulated by AMPK and Is Required for a Brown Adipose Phenotype
Ahmadian, M., Abbott, M. J., Tang, T., Hudak, C. S. S., Kim, Y., Bruss, M. D., Hellerstein, M. K., Lee, H., Samuel, V. T., Shulman, G. I., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.05.002 · Cited by 526 · see citing works
Adipose-Specific Knockout of raptor Results in Lean Mice with Enhanced Mitochondrial Respiration
Polak, P., Cybulski, N., Feige, J. N., Auwerx, J., Rüegg, M. A., & Hall, M. N. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.09.003 · Cited by 480 · see citing works
Obesity in mice with adipocyte-specific deletion of clock component Arntl
Paschos, G. K., Ibrahim, S., Song, W.-L., Kunieda, T., Grant, G., Reyes, T. M., Bradfield, C. A., Vaughan, C. H., Eiden, M., Masoodi, M., et al. (2012) · Nature Medicine · doi:10.1038/nm.2979 · Cited by 465 · see citing works
The basal proton conductance of mitochondria depends on adenine nucleotide translocase content
Brand, M. D., Pakay, J. L., Ocloo, A., Kokoszka, J., Wallace, D. C., Brookes, P. S., & Cornwall, E. J. (2005) · Biochemical Journal · doi:10.1042/bj20050890 · Cited by 410 · see citing works
Deng, T., Lyon, C. J., Minze, L. J., Lin, J., Zou, J., Liu, J. Z., Ren, Y., Yin, Z., Hamilton, D. J., Reardon, P. R., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.02.009 · Cited by 382 · see citing works
Increased Macrophage Migration Into Adipose Tissue in Obese Mice
Oh, D. Y., Morinaga, H., Talukdar, S., Bae, E. J., & Olefsky, J. M. (2011) · Diabetes · doi:10.2337/db11-0860 · Cited by 365 · see citing works
Self-citationChalkiadaki, A., & Guarente, L. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.07.003 · Cited by 352 · see citing works
Krishnan, J., Danzer, C. F., Simka, T., Ukropec, J., Walter, K., Kumpf, S., Mirtschink, P., Ukropcová, B., Gašperíková, D., Pedrazzini, T., et al. (2012) · Genes & Development · doi:10.1101/gad.180406.111 · Cited by 316 · see citing works
Lactate production in adipose tissue; a regulated function with extra‐adipose implications
DiGirolamo, M., Newby, F. D., & Lovejoy, J. C. (1992) · The FASEB Journal · doi:10.1096/fasebj.6.7.1563593 · Cited by 281 · see citing works
Jiang, C., Qu, A., Matsubara, T., Chanturiya, T., Jou, W., Gavrilova, O., Shah, Y. M., & Gonzalez, F. J. (2011) · Diabetes · doi:10.2337/db11-0174 · Cited by 268 · see citing works
Li, P., Fan, W., Xu, J., Lu, M. M., Yamamoto, H., Auwerx, J. H., Sears, D. D., Talukdar, S., Oh, D., Chen, A., et al. (2011) · Cell · doi:10.1016/j.cell.2011.09.050 · Cited by 264 · see citing works
Self-citationS-Nitrosylation-dependent Inactivation of Akt/Protein Kinase B in Insulin Resistance
Yasukawa, T., Tokunaga, E., Ota, H., Sugita, H., Martyn, J. A. J., & Kaneki, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411871200 · Cited by 262 · see citing works
Selective Inhibition of Hypoxia-Inducible Factor 1α Ameliorates Adipose Tissue Dysfunction
Sun, K., Halberg, N., Khan, M., Magalang, U. J., & Scherer, P. E. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00951-12 · Cited by 231 · see citing works
Lee, Y. S., Kim, A., Choi, J. W., Kim, M., Yasue, S., Son, H. J., Masuzaki, H., Park, K. S., & Kim, J. B. (2008) · Molecular Endocrinology · doi:10.1210/me.2008-0023 · Cited by 184 · see citing works
Self-citationSpite, M. R., Hellmann, J. L., Tang, Y., Mathis, S., Kosuri, M., Bhatnagar, A., Jala, V. R., & Haribabu, B. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100196 · Cited by 177 · see citing works
Endothelial Cell HIF-1α and HIF-2α Differentially Regulate Metastatic Success
Branco-Price, C., Zhang, N., Schnelle, M., Evans, C., Katschinski, D. M., Liao, D., Ellies, L., & Johnson, R. S. (2012) · Cancer Cell · doi:10.1016/j.ccr.2011.11.017 · Cited by 168 · see citing works
Self-citationThe immune system's involvement in obesity-driven type 2 diabetes
Shu, C. J., Benoist, C. O., & Mathis, D. J. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.12.001 · Cited by 165 · see citing works
Carboxyatractylate inhibits the uncoupling effect of free fatty acids
Andreyev, A. Y., BONDAREVA, T. O., Dedukhova, V. I., MOKHOVA, E. N., Skulachev, V. P., & Волков, Н. И. (1988) · FEBS Letters · doi:10.1016/0014-5793(88)81436-4 · Cited by 149 · see citing works
Sato, Y., Endo, H., Okuyama, H., Takeda, T., Iwahashi, H., Imagawa, A., Yamagata, K., Shimomura, I., & Inoue, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.194738 · Cited by 145 · see citing works
The Fractalkine/CX3CR1 System Regulates β Cell Function and Insulin Secretion
Lee, Y. S., Morinaga, H., Kim, J. J., Lagakos, W., Taylor, S., Keshwani, M., Perkins, G., Dong, H., Kayali, A. G., Sweet, I. R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.001 · Cited by 141 · see citing works
Self-citationLee, Y. S., Choi, J. W., Hwang, I., Lee, J. W., Lee, J. H., Kim, A. Y., Huh, J. Y., Koh, Y. J., Koh, G. Y., Son, H. J., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.085464 · Cited by 131 · see citing works
Self-citationDoege, K., Heine, S., Jensen, I., Jelkmann, W., & Metzen, E. (2005) · Blood · doi:10.1182/blood-2005-03-1138 · Cited by 128 · see citing works
Sims, K. H., Haynes, C. A., Kelly, S. L., Allegood, J. C., Wang, E. L., Momin, A. A., Leipelt, M., Reichart, D. R., Glass, C. K., Sullards, M. C., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.170621 · Cited by 126 · see citing works
Zhang, 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
Melillo, G., Taylor, L. S., Brooks, A., Cox, G. W., & Varesio, L. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.6.2638 · Cited by 104 · see citing works
Adenine nucleotide translocase: a component of the phylogenetically conserved cell death machinery
Zhivotovsky, B., Galluzzi, L., Kepp, O., & Kroemer, G. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.118 · Cited by 99 · see citing works
Lee, K. Y., Gesta, S., Boucher, J., Wang, X. L., & Kahn, C. R. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.006 · Cited by 92 · see citing works
Gonsalves, C. S., & Kalra, V. K. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902594 · Cited by 76 · see citing works
Qvisth, V., Toft, E., Moberg, E., Sjöberg, S., & Bolinder, J. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00104.2006 · Cited by 69 · see citing works
Transcriptional Cofactor TBLR1 Controls Lipid Mobilization in White Adipose Tissue
Rohm, M., Sommerfeld, A., Strzoda, D., Jones, A., Sijmonsma, T., Rudofsky, G., Wolfrum, C., Sticht, C., Gretz, N., Zeyda, M., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.02.010 · Cited by 59 · see citing works
Adipose-specific Lipoprotein Lipase Deficiency More Profoundly Affects Brown than White Fat Biology
Garcia-Arcos, I., Hiyama, Y., Drosatos, K., Bharadwaj, K. G., Hu, Y., Son, N. H., O'Byrne, S. M., Chang, C. L., Deckelbaum, R. J., Takahashi, M., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.469270 · Cited by 59 · see citing works
Sridharan, V., Guichard, J. L., Li, C., Muise‐Helmericks, R. C., Beeson, C. C., & Wright, G. L. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00466.2007 · Cited by 57 · see citing works
Leibel, R. L., Hirsch, J., Berry, E., & Gruen, R. (1985) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/42.2.198 · Cited by 47 · see citing works
Li, P., Fan, W., Xu, J., Lu, M. M., Yamamoto, H., Auwerx, J. H., Sears, D. D., Talukdar, S., Oh, D., Chen, A., et al. (2011) · Cited by 34 · see citing works
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Inflammatory mechanisms linking obesity and metabolic disease
Saltiel, A. R., & Olefsky, J. M. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92035 · Cited by 2,212 · see citing works
Self-citationInflammation 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 · see citing works
Self-citationAdipose 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 · see citing works
Adipose tissue dysfunction as determinant of obesity-associated metabolic complications
Longo, M., Zatterale, F., Naderi, J., Parrillo, L., Formisano, P., Raciti, G. A., Beguinot, F., & Miele, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092358 · Cited by 1,575 · see citing works
Adapting 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
The integrative biology of type 2 diabetes
Roden, M., & Shulman, G. I. (2019) · Nature · doi:10.1038/s41586-019-1797-8 · Cited by 1,167 · see citing works
Adipose-tissue plasticity in health and disease
Sakers, A. P., Siqueira, M. K. D., Seale, P., & Villanueva, C. J. (2022) · Cell · doi:10.1016/j.cell.2021.12.016 · Cited by 1,061 · see citing works
Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders
Choe, S. S., Huh, J. Y., Hwang, I. J., Kim, J. I., & Kim, J. B. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00030 · Cited by 1,206 · see citing works
Self-citationMetabolic Inflammation and Insulin Resistance in Obesity
Wu, H., & Ballantyne, C. M. (2020) · Circulation Research · doi:10.1161/circresaha.119.315896 · Cited by 1,059 · see citing works
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McNelis, J., & Olefsky, J. M. (2014) · Immunity · doi:10.1016/j.immuni.2014.05.010 · Cited by 728 · see citing works
Self-citationThe ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis.
Crewe, C., An, Y. A., & Scherer, P. E. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88883 · Cited by 732 · see citing works
The crucial role and mechanism of insulin resistance in metabolic disease
Zhao, X., An, X., Yang, C., Sun, W., Ji, H., & Lian, F. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1149239 · Cited by 630 · see citing works
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Quail, D. F., & Dannenberg, A. J. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0126-x · Cited by 542 · see citing works
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Rutkowski, J. M., Stern, J. H., & Scherer, P. E. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201409063 · Cited by 541 · see citing works
Emerging Targets in Type 2 Diabetes and Diabetic Complications
Demir, S., Nawroth, P. P., Herzig, S., & Üstünel, B. E. (2021) · Advanced Science · doi:10.1002/advs.202100275 · Cited by 544 · see citing works
Hypoxia signaling in human health and diseases: implications and prospects for therapeutics
Luo, Z., Tian, M., Yang, G., Tan, Q., Chen, Y., Li, G., Zhang, Q., Li, Y., Wan, P., & Wu, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01080-1 · Cited by 499 · see citing works
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Brestoff, J. R., & Artis, D. (2015) · Cell · doi:10.1016/j.cell.2015.02.022 · Cited by 498 · see citing works
An Integrated View of Immunometabolism
Lee, Y. S., Wollam, J., & Olefsky, J. M. (2018) · Cell · doi:10.1016/j.cell.2017.12.025 · Cited by 440 · see citing works
Self-citationAdipose tissue macrophages: going off track during obesity
Boutens, L., & Stienstra, R. (2016) · Diabetologia · doi:10.1007/s00125-016-3904-9 · Cited by 430 · see citing works
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Gonzalez, F., Xie, C., & Jiang, C.-T. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0096-z · Cited by 376 · see citing works
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Burhans, M. S., Hagman, D. K., Kuzma, J. N., Schmidt, K. A., & Kratz, M. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170040 · Cited by 427 · see citing works
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Görlach, A., Dimova, E. Y., Petry, A., Martı́nez-Ruiz, A., Hernansanz‐Agustín, P., Rolo, A. P., Palmeira, C. M., & Kietzmann, T. (2015) · Redox Biology · doi:10.1016/j.redox.2015.08.016 · Cited by 351 · see citing works
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Tang, Y., & Tsao, R. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201600767 · Cited by 342 · see citing works
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Chen, P.-S., Chiu, W.-T., Hsu, P.-L., Lin, S.-C., Peng, I.-C., Wang, C.-Y., & Tsai, S.-J. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-020-00658-7 · Cited by 318 · see citing works
Inter-organ crosstalk during development and progression of type 2 diabetes mellitus
Xourafa, G., Korbmacher, M., & Roden, M. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00898-1 · Cited by 274 · see citing works
Macrophage function in adipose tissue homeostasis and metabolic inflammation
Chavakis, T., Alexaki, V. I., & Ferrante, A. W. (2023) · Nature Immunology · doi:10.1038/s41590-023-01479-0 · Cited by 264 · see citing works
Hypoxia-Inducible Factors and Cancer
Jun, J. C., Rathore, A., Younas, H., Gilkes, D., & Polotsky, V. Y. (2017) · Current Sleep Medicine Reports · doi:10.1007/s40675-017-0062-7 · Cited by 248 · see citing works
The small intestine microbiota, nutritional modulation and relevance for health
El Aidy, S., van den Bogert, B., & Kleerebezem, M. (2015) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2014.09.005 · Cited by 244 · see citing works
Iron Metabolism in Obesity and Metabolic Syndrome
González-Domínguez, Á., Visiedo-García, F. M., Domínguez-Riscart, J., González-Domínguez, R., Mateos, R. M., & Lechuga-Sancho, A. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155529 · Cited by 227 · see citing works
Impact of Diabetes Mellitus on Bone Health
Murray, C. E., & Coleman, C. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194873 · Cited by 236 · see citing works
Inflammation in sleep apnea: An update
Unnikrishnan, D. C., Jun, J. C., & Polotsky, V. Y. (2014) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-014-9304-x · Cited by 225 · see citing works
An adipocentric perspective on the development and progression of non-alcoholic fatty liver disease
Lee, E., Korf, H., & Vidal‐Puig, A. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.01.024 · Cited by 228 · see citing works
Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential
Xiao, Y.-L., Gong, Y., Qi, Y.-J., Shao, Z., & Jiang, Y.-Z. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01771-x · Cited by 212 · see citing works
Feng, T., Zhao, X., Gu, P., Yang, W., Wang, C., Guo, Q., Long, Q., Liu, Q., Cheng, Y., Li, J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32871-3 · Cited by 190 · see citing works
Alcalá, M., Calderón‐Domínguez, M., Araya, M. E. B., Ramos, P., Casals, N., Serra, D., Viana, M., & Herrero, L. (2017) · Scientific Reports · doi:10.1038/s41598-017-16463-6 · Cited by 186 · see citing works
Is Mitochondrial Dysfunction a Common Root of Noncommunicable Chronic Diseases?
Díaz‐Vegas, A., Sánchez-Aguilera, P., Krycer, J. R., Morales, P. E., Monsalves‐Álvarez, M., Cifuentes, M., Rothermel, B. A., & Lavandero, S. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa005 · Cited by 174 · see citing works
Regulation of energy balance by inflammation: Common theme in physiology and pathology
Wang, H., & Ye, J. (2014) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-014-9306-8 · Cited by 173 · see citing works
Mayoral, R., Osborn, O., McNelis, J., Johnson, A. M., Oh, D. Y., Llorente, C., Chung, H., Li, P., Través, P. G., Bandyopadhyay, G. K., et al. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.02.007 · Cited by 170 · see citing works
Self-citationSingh, A. P., Shadangi, S., Gupta, P. K., & Rana, S. (2025) · Comprehensive physiology · doi:10.1002/cph4.70003 · Cited by 183 · see citing works
Angiogenesis in Adipose Tissue: The Interplay Between Adipose and Endothelial Cells
Herold, J. M., & Kalucka, J. M. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2020.624903 · Cited by 167 · see citing works
Fuchs, A. G., Samovski, D., Smith, G. I., Cifarelli, V., Farabi, S. S., Yoshino, J., Pietka, T., Chang, S.-W., Ghosh, S., Myckatyn, T. M., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.05.008 · Cited by 163 · see citing works
A click chemistry-mediated all-peptide cell printing hydrogel platform for diabetic wound healing
Huang, J., Yang, R., Jiao, J., Li, Z., Wang, P., Liu, Y., Li, S., Chen, C., Li, Z., Qu, G., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43364-2 · Cited by 162 · see citing works
Brown and Beige Adipose Tissues in Health and Disease
Rui, L. (2017) · Comprehensive physiology · doi:10.1002/cphy.c170001 · Cited by 178 · see citing works
Ryan, S. (2016) · The Journal of Physiology · doi:10.1113/jp273312 · Cited by 163 · see citing works
Adipocyte Piezo1 mediates obesogenic adipogenesis through the FGF1/FGFR1 signaling pathway in mice
Wang, S., Cao, S., Arhatte, M., Li, D., Shi, Y. X., Kurz, S., Hu, J., Wang, L., Shao, J., Atzberger, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16026-w · Cited by 152 · see citing works
Therapeutic Application of Betalains: A Review
Madadi, E., Mazloum-Ravasan, S., Yu, J. S., Ha, J. W., Hamishehkar, H., & Kim, K. H. (2020) · Plants · doi:10.3390/plants9091219 · Cited by 156 · see citing works
Biological plausibility linking sleep apnoea and metabolic dysfunction
Gileles‐Hillel, A., Gozal, D., & Gozal, D. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.22 · Cited by 148 · see citing works
Gout and Diet: A Comprehensive Review of Mechanisms and Management
Zhang, Y., Chen, S., Yuan, M., Xu, Y., & Xu, H. (2022) · Nutrients · doi:10.3390/nu14173525 · Cited by 164 · see citing works
Esteve, M. (2020) · Frontiers in Nutrition · doi:10.3389/fnut.2020.00111 · Cited by 142 · see citing works
Gérard, C., & Brown, K. A. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.09.014 · Cited by 136 · see citing works
Oxygenation of adipose tissue: A human perspective
Lempesis, I. G., van Meijel, R. L. J., Manolopoulos, K. N., & Goossens, G. H. (2019) · Acta Physiologica · doi:10.1111/apha.13298 · Cited by 138 · see citing works
Innate Immune Cells in the Adipose Tissue in Health and Metabolic Disease
Michailidou, Z., Gomez-Salazar, M. A., & Alexaki, V. I. (2021) · Journal of Innate Immunity · doi:10.1159/000515117 · Cited by 137 · see citing works
Lipid metabolism dysfunction induced by age-dependent DNA methylation accelerates aging
Li, X., Wang, J.-Q., Wang, L.-Y., Gao, Y., Feng, G.-H., Li, G., Zou, J., Yu, M., Li, Y., Liu, C., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00964-6 · Cited by 120 · see citing works
Killion, E. A., Reeves, A. R., ElAzzouny, M. A., Yan, Q.-W., Surujon, D., Griffin, J. D., Bowman, T. A., Wang, C., Matthan, N. R., Klett, E. L., et al. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.01.012 · Cited by 132 · see citing works
Decreased Adipose Tissue Oxygenation Associates with Insulin Resistance in Individuals with Obesity
Cifarelli, V., Beeman, S. C., Smith, G. I., Yoshino, J., Morozov, D., Beals, J. W., Kayser, B. D., Watrous, J. D., Jain, M., Patterson, B. W., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci141828 · Cited by 132 · see citing works
Insulin resistance, glucose intolerance and diabetes mellitus in obstructive sleep apnoea.
Kent, B. D., McNicholas, W. T., & Ryan, S. (2015) · PubMed Central · doi:10.3978/j.issn.2072-1439.2015.08.11 · Cited by 130 · see citing works
Engin, A. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_13 · Cited by 124 · see citing works
Inflammation‐mediated metabolic regulation in adipose tissue
Xu, S., Lu, F., Gao, J., & Yuan, Y. (2024) · Obesity Reviews · doi:10.1111/obr.13724 · Cited by 129 · see citing works
Ahechu, P., Zozaya, G., Martí, P., Hernández-Lizoáin, J. L., Baixauli, J., Unamuno, X., Frühbeck, G., & Catalán, V. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02918 · Cited by 129 · see citing works
Li, K., Xu, K., He, Y., Yang, Y., Tan, M., Mao, Y., Zou, Y., Feng, Q., Luo, Z. Y., & Cai, K. (2023) · ACS Nano · doi:10.1021/acsnano.2c10893 · Cited by 122 · see citing works
Obesity: A neuroimmunometabolic perspective
Larabee, C. M., Neely, O. C., & Domingos, A. I. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0283-6 · Cited by 123 · see citing works
Sex-based differences in insulin resistance
Gado, M., Tsaousidou, E., Bornstein, S. R., & Perakakis, N. (2024) · Journal of Endocrinology · doi:10.1530/joe-23-0245 · Cited by 125 · see citing works
HIF-1α in Myeloid Cells Promotes Adipose Tissue Remodeling Toward Insulin Resistance
Takikawa, A., Mahmood, A., Nawaz, A., Kado, T., Okabe, K., Yamamoto, S., Aminuddin, A., Senda, S., Tsuneyama, K., Ikutani, M., et al. (2016) · Diabetes · doi:10.2337/db16-0012 · Cited by 117 · see citing works
Abildgaard, J., Ploug, T., Al-Saoudi, E., Wagner, T., Thomsen, C., Ewertsen, C., Bzorek, M., Pedersen, B. K., Pedersen, A. T., & Lindegaard, B. (2021) · Scientific Reports · doi:10.1038/s41598-021-94189-2 · Cited by 116 · see citing works
Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis
Ouyang, X., Han, S., Zhang, J., Dioletis, E., Németh, B. T., Pacher, P., Feng, D., Bataller, R. A., Cabezas, J., Stärkel, P., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.01.007 · Cited by 115 · see citing works
Knockdown of ANT2 reduces adipocyte hypoxia and improves insulin resistance in obesity
Seo, J. B., Riopel, M., Cabrales, P., Huh, J. Y., Bandyopadhyay, G. K., Andreyev, A. Y., Murphy, A. N., Beeman, S. C., Smith, G. I., Klein, S., et al. (2018) · Nature Metabolism · doi:10.1038/s42255-018-0003-x · Cited by 113 · see citing works
Self-citationGruber, T., Pan, C., Contreras, R. E., Wiedemann, T., Morgan, D. A., Skowronski, A. A., Lefort, S., Murat, C. D. B., Thuc, O. L., Legutko, B., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.04.007 · Cited by 110 · see citing works
Epigenetic reprogramming in metabolic disorders: nutritional factors and beyond
Cheng, Z., Zheng, L., & Almeida, F. A. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2017.10.004 · Cited by 114 · see citing works
Caputo, T., Gilardi, F., & Desvergne, B. (2017) · FEBS Letters · doi:10.1002/1873-3468.12742 · Cited by 111 · see citing works
Macronutrients and the Adipose-Liver Axis in Obesity and Fatty Liver
Duwaerts, C. C., & Maher, J. J. (2019) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2019.02.001 · Cited by 109 · see citing works
Adipose tissue as a key player in obstructive sleep apnoea
Ryan, S., Arnaud, C., Fitzpatrick, S. F., Gaucher, J., Tamisier, R., & Pépin, J. (2019) · European Respiratory Review · doi:10.1183/16000617.0006-2019 · Cited by 107 · see citing works
Gabryelska, A., Karuga, F. F., Szmyd, B. M., & Białasiewicz, P. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.01035 · Cited by 106 · see citing works
Sharma, M., Boytard, L., Hadi, T., Koelwyn, G. J., Simon, R., Ouimet, M. I., Seifert, L., Spiro, W., Yan, B., Hutchison, S. B., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-62272-9 · Cited by 105 · see citing works
Paglialunga, S., Ludzki, A. C., Root-McCaig, J., & Holloway, G. P. (2015) · Diabetologia · doi:10.1007/s00125-015-3531-x · Cited by 104 · see citing works
Body composition and breast cancer risk and treatment: mechanisms and impact
Iwase, T., Wang, X., Shrimanker, T. V., Kolonin, M. G., & Ueno, N. T. (2021) · Breast Cancer Research and Treatment · doi:10.1007/s10549-020-06092-5 · Cited by 104 · see citing works
Glyoxalase 1 Modulation in Obesity and Diabetes
Rabbani, N., & Thornalley, P. J. (2019) · Antioxidants & Redox Signaling · doi:10.1089/ars.2017.7424 · Cited by 102 · see citing works
Inflammation, dysregulated metabolism and aromatase in obesity and breast cancer
Zahid, H., Simpson, E. R., & Brown, K. A. (2016) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2016.11.003 · Cited by 100 · see citing works
Warbrick, I., & Rabkin, S. W. (2019) · Obesity Reviews · doi:10.1111/obr.12828 · Cited by 97 · see citing works
Critical Role of Matrix Metalloproteinase 14 in Adipose Tissue Remodeling during Obesity
Li, X., Zhao, Y., Chen, C., Yang, L., Lee, H.-H., Wang, Z., Zhang, N., Kolonin, M. G., An, Z., Ge, X., et al. (2020) · Molecular and Cellular Biology · doi:10.1128/mcb.00564-19 · Cited by 100 · see citing works
Aging adipose: Depot location dictates age-associated expansion and dysfunction
Bank, H. C. V., Kirsh, C., & Simcox, J. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101259 · Cited by 100 · see citing works
Hong, H., Han, H., Wang, L., Cao, W., Hu, M., Li, J., Wang, J., Yang, Y., Xu, X., Li, G., et al. (2025) · Cell Death and Differentiation · doi:10.1038/s41418-024-01436-w · Cited by 100 · see citing works
Lin, Y., Bai, M., Wang, S., Chen, L., Li, Z., Li, C., Cao, P., & Chen, Y. (2022) · Diabetes · doi:10.2337/db21-0535 · Cited by 99 · see citing works
Hypoxia in Obesity and Diabetes: Potential Therapeutic Effects of Hyperoxia and Nitrate
Norouzirad, R., González‐Muniesa, P., & Ghasemi, A. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/5350267 · Cited by 96 · see citing works
Gaspar, J. M., & Velloso, L. A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00813 · Cited by 94 · see citing works
Miao, H., Chen, L., Hao, L., Zhang, X., Chen, Y., Ruan, Z., & Liang, H. (2015) · Scientific Reports · doi:10.1038/srep13092 · Cited by 96 · see citing works
Sleep Apnea and Sleep Habits: Relationships with Metabolic Syndrome
Borel, A. (2019) · Nutrients · doi:10.3390/nu11112628 · Cited by 93 · see citing works
Obesity promotes the expansion of metastasis-initiating cells in breast cancer
Bousquenaud, M., Fico, F., Solinas, G., Rüegg, C., & Santamaria‐Martínez, A. (2018) · Breast Cancer Research · doi:10.1186/s13058-018-1029-4 · Cited by 91 · see citing works
Dicarbonyl Stress at the Crossroads of Healthy and Unhealthy Aging
Nigro, C., Leone, A., Fiory, F., Prevenzano, I., Nicolò, A., Mirra, P., Bèguinot, F., & Miele, C. (2019) · Cells · doi:10.3390/cells8070749 · Cited by 91 · see citing works
The ambiguous role of obesity in oncology by promoting cancer but boosting antitumor immunotherapy
Assumpção, J. A. F., Pasquarelli-do-Nascimento, G., Viegas, M. S., Bonamino, M., & Magalhães, K. G. (2022) · Journal of Biomedical Science · doi:10.1186/s12929-022-00796-0 · Cited by 94 · see citing works
Hypoxia Potentiates Palmitate-induced Pro-inflammatory Activation of Primary Human Macrophages
Snodgrass, R. G., Boß, M., Zezina, E. A., Weigert, A., Dehne, N., Fleming, I., Brüne, B., & Namgaladze, D. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.686709 · Cited by 90 · see citing works
Pathologic HIF1α signaling drives adipose progenitor dysfunction in obesity
Shao, M., Hepler, C., Zhang, Q., Shan, B., Vishvanath, L., Henry, G. H., Zhao, S., An, Y., Wu, Y., Strand, D. W., et al. (2021) · Cell stem cell · doi:10.1016/j.stem.2020.12.008 · Cited by 86 · see citing works
Adipose Tissue Macrophage Polarization in Healthy and Unhealthy Obesity
Ruggiero, A. D., Key, C.-C. C., & Kavanagh, K. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.625331 · Cited by 89 · see citing works
- Authors
- Lee, Y. S., Kim, J.-W., Osborne, O., Oh, D. Y., Sasik, R., Schenk, S., Chen, A., Chung, H., Murphy, A., Watkins, S. M., Quehenberger, O., Johnson, R. S., & Olefsky, J. M.
- Affiliations
- University of California San Diego (US)
- University of Cambridge (GB)
- Corresponding author
- Johnson, Randall S.
- Olefsky, Jerrold M.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 157
- Issue
- 6
- Pages
- 1339-1352
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4114226
- OpenAlex
- W2023289992
- Cited by
- 598
- References
- 51
- Citations by year
- 2026: 45 · 2025: 51 · 2024: 59 · 2023: 64 · 2022: 65 · 2021: 70 · 2020: 57 · 2019: 37 · 2018: 39 · 2017: 39 · 2016: 34 · 2015: 27 · 2014: 11
- FWCI
- 27.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Aging
- Wellcome Trust
- National Institutes of Health (DK-074868, P01-DK054441, DK-063491, DK-033651)
- National Institute of Child Health and Human Development (R01AG043120, R24HD050837)
- American Diabetes Association
- 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
- HIF-1α, adipose tissue hypoxia, adipose tissue inflammation, insulin resistance, obesity, high-fat diet, uncoupled respiration, ANT2, saturated fatty acids, mitochondrial respiration, glucose tolerance
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Animals, Fatty Acids, Inflammation, Insulin Resistance, Nitric Oxide, Obesity, Oxygen, Cell Hypoxia, Adipocytes, Mice, Knockout, Lactic Acid, Adenine Nucleotide Translocator 2, Mice, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit, Diet, High-Fat
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