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Adiponectin Inhibits Tumor Necrosis Factor-α–Induced Vascular Inflammatory Response via Caveolin-Mediated Ceramidase Recruitment and Activation
Open accessAbstract
Rationale: Anti-inflammatory and vascular protective actions of adiponectin are well recognized. However, many fundamental questions remain unanswered. Objective: The current study attempted to identify the adiponectin receptor subtype responsible for adiponectin’s vascular protective action and investigate the role of ceramidase activation in adiponectin anti-inflammatory signaling. Methods and Results: Adiponectin significantly reduced tumor necrosis factor (TNF)α–induced intercellular adhesion molecule-1 expression and attenuated TNFα-induced oxidative/nitrative stress in human umbilical vein endothelial cells. These anti-inflammatory actions were virtually abolished by adiponectin receptor 1 (AdipoR1-), but not AdipoR2-, knockdown (KD). Treatment with adiponectin significantly increased neutral ceramidase (nCDase) activity (3.7-fold; P <0.01). AdipoR1-KD markedly reduced globular adiponectin–induced nCDase activation, whereas AdipoR2-KD only slightly reduced. More importantly, small interfering RNA-mediated nCDase-KD markedly blocked the effect of adiponectin on TNFα-induced intercellular adhesion molecule-1 expression. AMP-activated protein kinase-KD failed to block adiponectin-induced nCDase activation and modestly inhibited adiponectin anti-inflammatory effect. In contrast, in caveolin-1 KD (Cav1-KD) cells, >87% of adiponectin-induced nCDase activation was lost. Whereas adiponectin treatment failed to inhibit TNFα-induced intercellular adhesion molecule-1 expression, treatment with sphingosine-1-phosphate or SEW (sphingosine-1-phosphate receptor agonist) remained effective in Cav1-KD cells. AdipoR1 and Cav1 colocalized and coprecipitated in human umbilical vein endothelial cells. Adiponectin treatment did not affect this interaction. There is weak basal Cav1/nCDase interaction, which significantly increased after adiponectin treatment. Knockout of AdipoR1 or Cav1 abolished the inhibitory effect of adiponectin on leukocyte rolling and adhesion in vivo. Conclusions: These results demonstrate for the first time that adiponectin inhibits TNFα-induced inflammatory response via Cav1-mediated ceramidase recruitment and activation in an AdipoR1-dependent fashion.
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“Elevated TNF directly inhibits adiponectin63, arresting muscle protein synthesis and mitochondrial processes64.”
From Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies (2018) · cites this paper as [63]
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Cites
Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., et al. (2002) · Nature Medicine · doi:10.1038/nm788 · Cited by 4,238
Cloning of adiponectin receptors that mediate antidiabetic metabolic effects
Yamauchi, T., Kamon, J., Ito, Y., Tsuchida, A., Yokomizo, T., Kita, S., Sugiyama, T., Miyagishi, M., Hara, K., Tsunoda, M., et al. (2003) · Nature · doi:10.1038/nature01705 · Cited by 3,176
Adiponectin and Adiponectin Receptors
Kadowaki, T., & Yamauchi, T. (2005) · Endocrine Reviews · doi:10.1210/er.2005-0005 · Cited by 2,634
Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus
Buse, J. B., Ginsberg, H. N., Bakris, G. L., Clark, N. G., Costa, F., Eckel, R., Fonseca, V., Gerstein, H. C., Grundy, S., Nesto, R. W., et al. (2007) · Diabetes Care · doi:10.2337/dc07-9917 · Cited by 1,055
Adiponectin Stimulates Production of Nitric Oxide in Vascular Endothelial Cells
Chen, H., Montagnani, M., Funahashi, T., Shimomura, I., & Quon, M. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307878200 · Cited by 995
Shibata, R., Sato, K., Pimentel, D. R., Takemura, Y., Kihara, S., Ohashi, K., Funahashi, T., Ouchi, N., & Walsh, K. (2005) · Nature Medicine · doi:10.1038/nm1295 · Cited by 982
Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin
Holland, W. L., Miller, R. A., Wang, Z. V., Sun, K., Barth, B. M., Bui, H. H., Davis, K. E., Bikman, B. T., Halberg, N., Rutkowski, J. M., et al. (2011) · Nature Medicine · doi:10.1038/nm.2277 · Cited by 892
Diabetes and Endothelial Dysfunction: A Clinical Perspective
Calles-Escandón, J., & Cipolla, M. J. (2001) · Endocrine Reviews · doi:10.1210/edrv.22.1.0417 · Cited by 657
Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus
Buse, J. B., Ginsberg, H. N., Bakris, G. L., Clark, N. G., Costa, F., Eckel, R. H., Fonseca, V. A., Gerstein, H. C., Grundy, S. M., Nesto, R. W., et al. (2006) · Circulation · doi:10.1161/circulationaha.106.179294 · Cited by 634
Combs, T. P., Pajvani, U. B., Berg, A. H., Lin, Y., Jelicks, L. A., Laplante, M., Nawrocki, A. R., Rajala, M. W., Parlow, A. F., Cheeseboro, L., et al. (2004) · Endocrinology · doi:10.1210/en.2003-1068 · Cited by 545
AMPK: A Key Sensor of Fuel and Energy Status in Skeletal Muscle
Hardie, D. G., & Sakamoto, K. (2006) · Physiology · doi:10.1152/physiol.00044.2005 · Cited by 536
Tao, L., Gao, E., Jiao, X., Yuan, Y., Li, S., Christopher, T. A., Lopez, B. L., Koch, W. J., Chan, L., Goldstein, B. J., et al. (2007) · Circulation · doi:10.1161/circulationaha.106.666941 · Cited by 452
Self-citationTNFα in atherosclerosis, myocardial ischemia/reperfusion and heart failure
Kleinbongard, P., Heusch, G., & Schulz, R. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.05.002 · Cited by 415
Theilmeier, G., Schmidt, C., Herrmann, J., Keul, P., Schäfers, M. A., Herrgott, I., Mersmann, J., Larmann, J., Hermann, S., Stypmann, J., et al. (2006) · Circulation · doi:10.1161/circulationaha.105.607135 · Cited by 414
Caveolin, Caveolae, and Endothelial Cell Function
Frank, P. G., Woodman, S. E., Park, D. S., & Lisanti, M. P. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000070546.16946.3a · Cited by 386
PAQR Proteins: A Novel Membrane Receptor Family Defined by an Ancient7-Transmembrane Pass Motif
Tang, Y., Hu, T., Arterburn, M., Boyle, B., Bright, J. M., Emtage, P. C. R., & Funk, W. D. (2005) · Journal of Molecular Evolution · doi:10.1007/s00239-004-0375-2 · Cited by 381
Hypoadiponectinemia Is Associated with Impaired Endothelium-Dependent Vasodilation
Tan, K. C. B., Xu, A., Chow, W.-S., Lam, M. C., Ai, V. H. G., Tam, S., & Lam, K. S. L. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031012 · Cited by 356
Hypoadiponectinemia Is Closely Linked to Endothelial Dysfunction in Man
Shimabukuro, M., Higa, N., Asahi, T., Oshiro, Y., Takasu, N., Tagawa, T., Ueda, S., Shimomura, I., Funahashi, T., & Matsuzawa, Y. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021883 · Cited by 349
T-cadherin is critical for adiponectin-mediated cardioprotection in mice
Denzel, M. S., Scimia, M. C., Zumstein, P., Walsh, K. X., Ruiz‐Lozano, P., & Ranscht, B. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43464 · Cited by 345
Caveolae, caveolins, and cavins: complex control of cellular signalling and inflammation
Chidlow, J. H., & Sessa, W. C. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq075 · Cited by 310
Adiponectin and cardiovascular health: an update
Hui, X. H., Lam, K. S., Vanhoutte, P. M., & Xu, A. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01395.x · Cited by 295
Protective vascular and myocardial effects of adiponectin
Goldstein, B. J., Scalia, R. G., & Ma, X. L. (2008) · Nature Clinical Practice Cardiovascular Medicine · doi:10.1038/ncpcardio1398 · Cited by 295
Self-citationOuedraogo, R., Gong, Y., Berzins, B., Wu, X., Mahadev, K., Hough, K., Chan, L., Goldstein, B. J., & Scalia, R. G. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29623 · Cited by 265
Self-citationMurata, T., Lin, M. I., Huang, Y., Yu, J., Bauer, P. M., Giordano, F. J., & Sessa, W. C. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062340 · Cited by 246
Keul, P., Lucke, S., Lipinski, K. V. W., Bode, C., Gräler, M. H., Heusch, G., & Levkau, B. (2010) · Circulation Research · doi:10.1161/circresaha.110.235028 · Cited by 233
Fernandez-Hernando, C. F., Yu, J., Suárez, Y., Rahner, C., Dávalos, A., Lasunción, M. A., & Sessa, W. C. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.06.003 · Cited by 192
Sphingosine 1-phosphate levels in plasma and HDL are altered in coronary artery disease
Sattler, K., Elbasan, Ş., Keul, P., Elter-Schulz, M., Bode, C., Gräler, M. H., Bröcker‐Preuß, M., Budde, T., Erbel, R., Heusch, G., et al. (2010) · Basic Research in Cardiology · doi:10.1007/s00395-010-0112-5 · Cited by 192
Tao, L., Gao, E., Bryan, N. S., Qu, Y., Liu, H., Hu, A., Christopher, T. A., Lopez, B. L., Yodoi, J., Koch, W. J., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402941101 · Cited by 190
Self-citationEndothelial-specific expression of caveolin-1 impairs microvascular permeability and angiogenesis
Bauer, P. M., Yu, J., Chen, Y., Hickey, R. P., Bernatchez, P. N., Looft‐Wilson, R. C., Huang, Y., Giordano, F. J., Stan, R. V., & Sessa, W. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406092102 · Cited by 169
Bruce, C. R., Mertz, V. A., Heigenhauser, G. J. F., & Dyck, D. J. (2005) · Diabetes · doi:10.2337/diabetes.54.11.3154 · Cited by 165
Altered Mitochondrial Function and Metabolic Inflexibility Associated with Loss of Caveolin-1
Asterholm, I. W., Mundy, D. I., Weng, J., Anderson, R. G. W., & Scherer, P. E. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.01.004 · Cited by 157
Gonzalez, E., Nagiel, A., Lin, A. J., Golan, D. E., & Michel, T. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407051200 · Cited by 140
Wang, Y., Gao, E., Tao, L., Lau, W. B., Yuan, Y., Goldstein, B. J., Lopez, B. L., Christopher, T. A., Tian, R., Koch, W. J., et al. (2009) · Circulation · doi:10.1161/circulationaha.108.815043 · Cited by 136
Self-citationRatajczak, P. (2003) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00660-0 · Cited by 132
Fujioka, D., Kawabata, K.-I., Saito, Y., Kobayashi, T., Nakamura, T., Kodama, Y., Takano, H., Obata, J.-E., Kitta, Y., Umetani, K., et al. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00987.2005 · Cited by 115
Wang, Y., Lau, W. B., Gao, E., Tao, L., Yuan, Y., Li, R., Wang, X., Koch, W. J., & Ma, X. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00663.2009 · Cited by 108
Self-citationCeramide: Physiological and pathophysiological aspects
Schenck, M., Carpinteiro, A., Grassmé, H., Lang, F. J. W., & Gulbins, E. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2007.03.031 · Cited by 104
Tamura, D. Y., Moore, E. E., Johnson, J. L., Zallen, G. S., Aiboshi, J., & Silliman, C. C. (1998) · Surgery · doi:10.1016/s0039-6060(98)70147-3 · Cited by 90
Razani, B., & Lisanti, M. P. (2001) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2001.281.4.c1241 · Cited by 87
Bedia, C., Camacho, L., Abad, J. L., Fabriàs, G., & Levade, T. (2010) · Journal of Lipid Research · doi:10.1194/jlr.d010033 · Cited by 69
Adiponectin Receptor Signaling: A New Layer to the Current Model
Kadowaki, T., & Yamauchi, T. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.01.012 · Cited by 65
Ceramide: A Novel Player in Reactive Oxygen Species-Induced Signaling?
Dumitru, C. A., Zhang, Y., Li, X., & Gulbins, E. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1692 · Cited by 64
Kupchak, B. R., Garitaonandia, I., Villa, N., Smith, J. L., & Lyons, T. J. (2009) · Biochemistry · doi:10.1021/bi9006258 · Cited by 58
Tani, M., Igarashi, Y., & Ito, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506827200 · Cited by 50
Adipokines and vascular disease in diabetes
Goldstein, B. J., & Scalia, R. G. (2007) · Current Diabetes Reports · doi:10.1007/s11892-007-0006-6 · Cited by 49
Self-citationWang, Y., Tao, L., Yuan, Y., Lau, W. B., Li, R., Lopez, B. L., Christopher, T. A., Tian, R., & Ma, X.-L. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90975.2008 · Cited by 47
Self-citationEssential Role of Caveolin-3 in Adiponectin Signalsome Formation and Adiponectin Cardioprotection
Wang, Y., Wang, X., Jasmin, J.-F., Lau, W. B., Li, R., Yuan, Y., Yi, W., Chuprun, K. J., Lisanti, M. P., Koch, W. J., et al. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.242164 · Cited by 46
Self-citationAdiponectin identified as an agonist for PAQR3/RKTG using a yeast-based assay system
Garitaonandia, I., Smith, J. L., Kupchak, B. R., & Lyons, T. J. (2009) · Journal of Receptors and Signal Transduction · doi:10.1080/10799890902729456 · Cited by 36
Targeting adiponectin for cardioprotection
Ouchi, N., Shibata, R., & Walsh, K. X. (2006) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.10.4.573 · Cited by 33
Hypoadiponectinemia is Associated With Coronary Artery Spasm in Men
Maruyoshi, H., Kojima, S., Otsuka, F., Funahashi, T., Kaikita, K., Sugiyama, S., Sakamoto, T., Yoshimura, M., Shimomura, I., & Ogawa, H. (2005) · Circulation Journal · doi:10.1253/circj.69.1154 · Cited by 29
Aromatic residues of Caveolin-1 binding motif of α-hemolysin are essential for membrane penetration
Pany, S., & Krishnasastry, M. V. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.08.132 · Cited by 10
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Metadata
- Authors
- Wang, Y., Wang, X., Lau, W. B., Yuan, Y., Booth, D., Li, J.-J., Scalia, R., Preston, K., Gao, E., Koch, W., & Ma, X.-L.
- Affiliations
- Thomas Jefferson University (US)
- From the Department of Emergency Medicine (Y.W., X.W., W.B.L., Y.Y., J.-J.L., X.-L.M.) and Department of Pathology (D.B.), Thomas Jefferson University, Philadelphia, PA; and Department of Physiology, Cardiovascular Research Center (R.S., K.P.) and Center for Translational Medicine (E.G., W.K.), Temple University, Philadelphia, PA.
- Venue
- Circulation Research
- Published
- 2014-02-28
- Volume
- 114
- Issue
- 5
- Pages
- 792-805
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC3961763
- OpenAlex
- W2081966889
- Cited by
- 104
- References
- 51
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 8 · 2023: 9 · 2022: 9 · 2021: 11 · 2020: 12 · 2019: 7 · 2018: 9 · 2017: 12 · 2016: 11 · 2015: 4 · 2014: 4
- FWCI
- 7.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The Medicine Forum (submittedVersion)
- Funders
- National Institutes of Health (1s10od010408-01)
- National Heart, Lung, and Blood Institute (T32HL091804, HL 63828, R01HL063828, R01HL096686, P01HL108806, HL-096686)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK096521, R01DK064344)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- adiponectin, TNF-α, caveolin-1, neutral ceramidase, AdipoR1, AdipoR2, endothelial inflammation, ICAM-1, sphingosine-1-phosphate, AMPK, leukocyte adhesion, vascular inflammation, anti-inflammatory signaling, human umbilical vein endothelial cells
- MeSH terms
- Enzyme Activation, Humans, Tumor Necrosis Factor-alpha, Vasculitis, Signal Transduction, Reactive Oxygen Species, Reactive Nitrogen Species, RNA, Small Interfering, Leukocyte Rolling, Endothelial Cells, Caveolin 1, Adiponectin, Receptors, Adiponectin, Ceramidases, Gene Knockdown Techniques, Human Umbilical Vein Endothelial Cells
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