The Long Form of the Leptin Receptor Regulates STAT5 and Ribosomal Protein S6 via Alternate Mechanisms
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The action of leptin via the long form of its receptor (LepRb) is central to the control of body energy homeostasis and neuroendocrine function, but the mechanisms by which LepRb regulates intracellular signaling have remained incompletely understood. Here we demonstrate that leptin stimulates the phosphorylation of STAT5 and ribosomal protein S6 in the hypothalamic arcuate nucleus in mice. In cultured cells, we investigate the mechanisms by which leptin regulates each of these pathways. Our analysis reveals a dominant role for LepRb Tyr(1077) (which we demonstrate to be phosphorylated during receptor activation) and a secondary role for LepRb Tyr(1138) in the acute phosphorylation of STAT5a and STAT5b. Tyr(1138) and STAT3 attenuate STAT5-dependent transcription over the long-term, however. In contrast, Tyr(985) (the LepRb phosphorylation site required for ERK activation) mediates the phosphorylation of the ribosomal S6 kinase (RSK) and S6, as well as cap-dependent translation. Thus, these data demonstrate the phosphorylation of Tyr(1077) on LepRb during receptor activation, substantiate the hypothalamic regulation of STAT5 and S6 by leptin, and define the alternate LepRb signaling pathways that mediate each of these signals and their effects in cultured cells. Dissecting the contributions of these individual pathways to leptin action will be important for our ultimate understanding of the processes that regulate energy balance in vivo.
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Phosphorylation of Tyr1077 and Tyr1138 promotes recruitment, phosphorylation, and transcriptional activation of STAT5.
“Phosphorylation of Tyr1077 and Tyr1138 promote the recruitment, phosphorylation and transcriptional activation of STAT5 (71)”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [71]
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
Prevalence of Overweight and Obesity in the United States, 1999-2004
Ogden, C. L., Carroll, M. D., Curtin, L. R., McDowell, M. A., Tabak, C. J., & Flegal, K. M. (2006) · JAMA · doi:10.1001/jama.295.13.1549 · Cited by 8,720 · see citing works
Darnell, J. E., Kerr, L. M., & Stark, G. R. (1994) · Science · doi:10.1126/science.8197455 · Cited by 6,080 · see citing works
Leptin and the regulation of body weight in mammals
Friedman, J. M., & Halaas, J. L. (1998) · Nature · doi:10.1038/27376 · Cited by 5,405 · see citing works
Identification and expression cloning of a leptin receptor, OB-R.
Tartaglia, L. A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G. J., Campfield, L. A., Clark, F. T., Deeds, J., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90151-5 · Cited by 3,496 · see citing works
Role of leptin in the neuroendocrine response to fasting
Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996) · Nature · doi:10.1038/382250a0 · Cited by 3,117 · see citing works
Zhong, Z., Wen, Z., & Darnell, J. E. (1994) · Science · doi:10.1126/science.8140422 · Cited by 2,070 · see citing works
Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
Minokoshi, Y., Kim, Y.-B., Peroni, O. D., Fryer, L. G. D., Müller, C., Carling, D., & Kahn, B. B. (2002) · Nature · doi:10.1038/415339a · Cited by 2,053 · see citing works
SH2 and SH3 Domains: Elements that Control Interactions of Cytoplasmic Signaling Proteins
Koch, C. A., Anderson, D. H., Moran, M. F., Ellis, C. A., & Pawson, T. J. (1991) · Science · doi:10.1126/science.1708916 · Cited by 1,868 · see citing works
AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus
Minokoshi, Y., Alquier, T., Furukawa, N., Kim, Y.-B., Lee, A., Xue, B., Mu, J., Foufelle, F., Ferré, P., Birnbaum, M. J., et al. (2004) · Nature · doi:10.1038/nature02440 · Cited by 1,637 · see citing works
Lifetime risk for diabetes mellitus in the United States
Narayan, K. M. V. (2003) · JAMA · doi:10.1001/jama.290.14.1884 · Cited by 1,515 · see citing works
Hypothalamic mTOR Signaling Regulates Food Intake
Cota, D., Proulx, K., Smith, K. A. B., Kozma, S. C., Thomas, G., Woods, S. C., & Seeley, R. J. (2006) · Science · doi:10.1126/science.1124147 · Cited by 1,278 · see citing works
Holz, M. K., Ballif, B. A., Gygi, S. P., & Blenis, J. (2005) · Cell · doi:10.1016/j.cell.2005.10.024 · Cited by 1,262 · see citing works
Fingar, D. C., & Blenis, J. (2004) · Oncogene · doi:10.1038/sj.onc.1207542 · Cited by 1,250 · see citing works
Self-citationLeptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice.
Vaisse, C., Halaas, J. L., Horvath, C. M., Darnell, J. E., Stoffel, M., & Friedman, J. M. (1996) · Nature Genetics · doi:10.1038/ng0996-95 · Cited by 1,086 · see citing works
Phenotypes of Mouse diabetes and Rat fatty Due to Mutations in the OB (Leptin) Receptor
Chua, S. C., Chung, W. K., Wu-Peng, X. S., Zhang, Y., Liu, S.-M., Tartaglia, L. A., & Leibel, R. L. (1996) · Science · doi:10.1126/science.271.5251.994 · Cited by 1,071 · see citing works
STAT3 signalling is required for leptin regulation of energy balance but not reproduction
Bates, S. H., Stearns, W. H., Dundon, T. A., Schubert, M., Tso, A. W. K., Wang, Y., Banks, A. S., Lavery, H. J., Haq, A. K., Maratos-Flier, E., et al. (2003) · Nature · doi:10.1038/nature01388 · Cited by 1,010 · see citing works
Self-citationTwo defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity
El-Haschimi, K., Pierroz, D. D., Hileman, S. M., Bjørbæk, C., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9842 · Cited by 887 · see citing works
The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors.
Baumann, H., Morella, K. K., White, D. W., Dembski, M., Bailon, P., Kim, H., Lai, C. F., & Tartaglia, L. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8374 · Cited by 810 · see citing works
Activation of Downstream Signals by the Long Form of the Leptin Receptor
Banks, A. S., Davis, S. M., Bates, S. H., & Myers, M. G. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.19.14563 · Cited by 797 · see citing works
Self-citationDefective STAT signaling by the leptin receptor in diabetic mice.
Ghilardi, N., Ziegler, S., Wiestner, A. C., Stoffel, R., Heim, M. H., & Skoda, R. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.13.6231 · Cited by 793 · see citing works
Ribosomal protein S6 phosphorylation: from protein synthesis to cell size
Ruvinsky, I., & Meyuhas, O. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.04.003 · Cited by 780 · see citing works
Roux, P. P., Ballif, B. A., Anjum, R., Gygi, S. P., & Blenis, J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405659101 · Cited by 750 · see citing works
Roux, P. P., Shahbazian, D., Vu, H., Holz, M. K., Cohen, M. S., Taunton, J., Sonenberg, N., & Blenis, J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700906200 · Cited by 749 · see citing works
Pende, M., Um, S. H., Mieulet, V., Sticker, M., Goss, V. L., Mestan, J., Mueller, M., Fumagalli, S., Kozma, S. C., & Thomas, G. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.8.3112-3124.2004 · Cited by 743 · see citing works
Region-Specific Leptin Resistance within the Hypothalamus of Diet-Induced Obese Mice
Münzberg, H., Flier, J. S., & Bjørbæk, C. (2004) · Endocrinology · doi:10.1210/en.2004-0726 · Cited by 737 · see citing works
Self-citationFetal Anemia and Apoptosis of Red Cell Progenitors in Stat5a−/−5b−/− Mice
Socolovsky, M., Fallon, A. E. J., Wang, S., Brugnara, C., & Lodish, H. F. (1999) · Cell · doi:10.1016/s0092-8674(00)81013-2 · Cited by 695 · see citing works
Selective deletion of leptin receptor in neurons leads to obesity
Cohen, P., Zhao, C., Cai, X., Montez, J. M., Rohani, S., Feinstein, P. G., Mombaerts, P., & Friedman, J. M. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13914 · Cited by 657 · see citing works
Key enzyme in leptin-induced anorexia
Niswender, K. D., Morton, G. J., Stearns, W. H., Rhodes, C. J., Myers, M. G., & Schwartz, M. W. (2001) · Nature · doi:10.1038/35101657 · Cited by 585 · see citing works
Self-citationSelective deletion of leptin receptor in neurons leads to obesity
Cohen, P., Zhao, C., Cai, X., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200113914 · Cited by 554 · see citing works
SOCS3 Mediates Feedback Inhibition of the Leptin Receptor via Tyr985
Bjørbæk, C., Lavery, H. J., Bates, S. H., Olson, R. K., Davis, S. M., Flier, J. S., & Myers, M. G. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m007577200 · Cited by 537 · see citing works
Self-citationUnraveling the central nervous system pathways underlying responses to leptin
Elmquist, J. K., Maratos-Flier, E., Saper, C. B., & Flier, J. S. (1998) · Nature Neuroscience · doi:10.1038/2164 · Cited by 520 · see citing works
Leptin Receptor Signaling and the Regulation of Mammalian Physiology
Myers, M. G. (2004) · Recent Progress in Hormone Research · doi:10.1210/rp.59.1.287 · Cited by 458 · see citing works
Self-citationPI3K integrates the action of insulin and leptin on hypothalamic neurons
Xu, A. W. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200524301 · Cited by 420 · see citing works
Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasis
Elmquist, J. K., Coppari, R., Balthasar, N., Ichinose, M., & Lowell, B. B. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20786 · Cited by 388 · see citing works
Proliferation, But Not Growth, Blocked by Conditional Deletion of 40 S Ribosomal Protein S6
Volarević, S., Stewart, M. J., Ledermann, B., Zilbermann, F., Terracciano, L., Montini, E., Grompe, M., Kozma, S. C., & Thomas, G. (2000) · Science · doi:10.1126/science.288.5473.2045 · Cited by 372 · see citing works
Divergent Roles of SHP-2 in ERK Activation by Leptin Receptors
Bjørbæk, C., Buchholz, R. M., Davis, S. M., Bates, S. H., Pierroz, D. D., Gu, H., Neel, B. G., Myers, M. G., & Flier, J. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007439200 · Cited by 364 · see citing works
Self-citationFunctional Roles of STAT Family Proteins: Lessons from Knockout Mice
Akira, S. (1999) · Stem Cells · doi:10.1002/stem.170138 · Cited by 349 · see citing works
CIS3/SOCS-3 Suppresses Erythropoietin (EPO) Signaling by Binding the EPO Receptor and JAK2
Sasaki, A. T., Yasukawa, H., Shouda, T., Kitamura, T., Đikić, I., & Yoshimura, A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003456200 · Cited by 341 · see citing works
Plum, L. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27123 · Cited by 326 · see citing works
Leptin Receptor (OB-R) Signaling
White, D. W., Kuropatwinski, K. K., Devos, R., Baumann, H., & Tartaglia, L. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.7.4065 · Cited by 293 · see citing works
Leptin receptor action and mechanisms of leptin resistance
Münzberg, H., Björnholm, M., Bates, S. H., & Myers, M. G. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-4432-1 · Cited by 261 · see citing works
Self-citationRegulation of Jak Kinases by Intracellular Leptin Receptor Sequences
Kloek, C. E., Haq, A. K., Dunn, S. L., Lavery, H. J., Banks, A. S., & Myers, M. G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205148200 · Cited by 233 · see citing works
Self-citationGeneral nature of the STAT3-activated anti-inflammatory response.
El Kasmi, K. C., Holst, J., Coffre, M., Mielke, L., de Pauw, A., Lhocine, N., Smith, A. M., Rutschman, R., Kaushal, D., Shen, Y., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.11.7880 · Cited by 225 · see citing works
Self-citationLeptin Receptor Signaling and Action in the Central Nervous System
Leshan, R. L., Björnholm, M., Münzberg, H., & Myers, M. G. (2006) · Obesity · doi:10.1038/oby.2006.310 · Cited by 221 · see citing works
Self-citationMonogenic Human Obesity Syndromes
Farooqi, I. S. (2004) · Recent Progress in Hormone Research · doi:10.1210/rp.59.1.409 · Cited by 170 · see citing works
Dunn, S. L., Björnholm, M., Bates, S., Chen, Z., Seifert, M. M., & Myers, M. G. (2005) · Molecular Endocrinology · doi:10.1210/me.2004-0353 · Cited by 169 · see citing works
Self-citationBanks, W. A. (2004) · Peptides · doi:10.1016/j.peptides.2004.02.014 · Cited by 153 · see citing works
Transgenic Complementation of Leptin-Receptor Deficiency
Kowalski, T. J., Liu, S.-M., Leibel, R. L., & Chua, S. C. (2001) · Diabetes · doi:10.2337/diabetes.50.2.425 · Cited by 150 · see citing works
Identification of the Y985 and Y1077 motifs as SOCS3 recruitment sites in the murine leptin receptor
Eyckerman, S., Broekaert, D., Verhee, A., Vandekerckhove, J. S., & Tavernier, J. H. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)02205-5 · Cited by 142 · see citing works
LRb-STAT3 Signaling Is Required for the Neuroendocrine Regulation of Energy Expenditure by Leptin
Bates, S. H., Dundon, T. A., Seifert, M., Carlson, M., Maratos-Flier, E., & Myers, M. G. (2004) · Diabetes · doi:10.2337/diabetes.53.12.3067 · Cited by 139 · see citing works
Self-citationPleiotropy of leptin receptor signalling is defined by distinct roles of the intracellular tyrosines
Hekerman, P., Zeidler, J., Bamberg‐Lemper, S., Knobelspies, H., Lavens, D., Tavernier, J., Joost, H., & Becker, W. (2004) · The FEBS Journal · doi:10.1111/j.1432-1033.2004.04391.x · Cited by 129 · see citing works
Cellular Warriors at the Battle of the Bulge
Marx, J. (2003) · Science · doi:10.1126/science.299.5608.846 · Cited by 121 · see citing works
Bergad, P. L., Shih, H., Towle, H. C., Schwarzenberg, S. J., & Berry, S. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.42.24903 · Cited by 117 · see citing works
Leptin as a Therapeutic Agent--Trials and Tribulations
Mantzoros, C. S., & Flier, J. S. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.11.7062 · Cited by 115 · see citing works
Tyrosine Phosphorylation of Jak2 in the JH2 Domain Inhibits Cytokine Signaling
Feener, E. P., Rosario, F., Dunn, S. L., Stancheva, Z. S., & Myers, M. G. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.11.4968-4978.2004 · Cited by 113 · see citing works
Self-citationStructure of the Mouse Stat 3/5 Locus: Evolution from Drosophila to Zebrafish to Mouse
Miyoshi, K., Cui, Y., Riedlinger, G., Robinson, P. R., Lehoczky, J. A., Zon, L. I., Oka, T., Dewar, K., & Hennighausen, L. G. (2001) · Genomics · doi:10.1006/geno.2000.6433 · Cited by 67 · see citing works
A complex interaction pattern of CIS and SOCS2 with the leptin receptor
Lavens, D., Montoye, T., Piessevaux, J., Zabeau, L., Vandekerckhove, J. S., Gevaert, K., Becker, W. B., Eyckerman, S., & Tavernier, J. H. (2006) · Journal of Cell Science · doi:10.1242/jcs.02947 · Cited by 60 · see citing works
Rizk, N. M., Stammsen, D., Preibisch, G., & Eckel, J. (2001) · Endocrinology · doi:10.1210/endo.142.7.8225 · Cited by 35 · see citing works
Leading Causes of Death in the United States
Tierney, E. F. (2006) · JAMA · doi:10.1001/jama.295.4.383-a · Cited by 28 · see citing works
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Mechanisms of leptin action and leptin resistance.
Myers, M. G., Cowley, M. A., & Münzberg, H. (2008) · Annual Review of Physiology · doi:10.1146/annurev.physiol.70.113006.100707 · Cited by 1,074 · see citing works
Self-citationObesity and leptin resistance: distinguishing cause from effect
Myers, M. G., Leibel, R. L., Seeley, R. J., & Schwartz, M. W. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.08.002 · Cited by 906 · see citing works
Self-citationThe cellular and molecular bases of leptin and ghrelin resistance in obesity
Cui, H., López, M., & Rahmouni, K. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.222 · Cited by 482 · see citing works
Recent advances in understanding leptin signaling and leptin resistance
Morris, D. L., & Rui, L. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00274.2009 · Cited by 467 · see citing works
Leptin signaling and leptin resistance
Zhou, Y., & Rui, L. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0263-5 · Cited by 417 · see citing works
Leptin Indirectly Regulates Gonadotropin-Releasing Hormone Neuronal Function
Quennell, J. H., Mulligan, A. C., Tups, A., Liu, X., Phipps, S. J., Kemp, C. J., Herbison, A. E., Grattan, D. R., & Anderson, G. M. (2009) · Endocrinology · doi:10.1210/en.2008-1693 · Cited by 385 · see citing works
Leptin and the Central Nervous System Control of Glucose Metabolism
Morton, G. J., & Schwartz, M. W. (2011) · Physiological Reviews · doi:10.1152/physrev.00007.2010 · Cited by 338 · see citing works
“Recent evidence suggests that leptin is capable of activating STAT5 in the hypothalamic arcuate nucleus (ARC) in vivo (126), in addition to cultured cells (71), raising the possibility that LepRb-STAT5 signaling contributes to the physiological actions of leptin.”
BackgroundInfluentialAdipokines and the Peripheral and Neural Control of Energy Balance
Ahima, R. S., & Lazar, M. A. (2008) · Molecular Endocrinology · doi:10.1210/me.2007-0529 · Cited by 314 · see citing works
The Role of Leptin and Adiponectin in Obesity-Associated Cognitive Decline and Alzheimer’s Disease
Forny‐Germano, L., Felice, F. G. D., & Vieira, M. N. N. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.01027 · Cited by 298 · see citing works
Leptin revisited: its mechanism of action and potential for treating diabetes
Coppari, R., & Bjørbæk, C. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3757 · Cited by 295 · see citing works
Leptin signalling pathways in hypothalamic neurons
Kwon, O., Kim, K. W., & Kim, M. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2133-1 · Cited by 283 · see citing works
Cross-talk between estrogen and leptin signaling in the hypothalamus
Gao, Q., & Horváth, T. L. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00733.2007 · Cited by 249 · see citing works
Evolution of Leptin Structure and Function
Denver, R. J., Bonett, R. M., & Boorse, G. C. (2011) · Neuroendocrinology · doi:10.1159/000328435 · Cited by 236 · see citing works
Leptin receptor signaling and the regulation of mammalian physiology
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Self-citationLeptin resistance in obesity: An epigenetic landscape
Crujeiras, A. B., Carreira, M. C., Fernández, B. C., Andrade, S., Amil, M., & Casanueva, F. F. (2015) · Life Sciences · doi:10.1016/j.lfs.2015.05.003 · Cited by 223 · see citing works
Altered hypothalamic function in diet-induced obesity
Velloso, L. A., & Schwartz, M. W. (2011) · International Journal of Obesity · doi:10.1038/ijo.2011.56 · Cited by 220 · see citing works
Ribosomal Protein S6 Phosphorylation in the Nervous System: From Regulation to Function
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Obesity as a Risk Factor for Dementia and Alzheimer’s Disease: The Role of Leptin
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Hypothalamic ERK Mediates the Anorectic and Thermogenic Sympathetic Effects of Leptin
Rahmouni, K., Sigmund, C. D., Haynes, W. G., & Mark, A. L. (2008) · Diabetes · doi:10.2337/db08-0822 · Cited by 207 · see citing works
Molecular and neural mediators of leptin action
Robertson, S., Leinninger, G. M., & Myers, M. G. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.04.005 · Cited by 186 · see citing works
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Wauman, J. (2011) · Frontiers in bioscience · doi:10.2741/3885 · Cited by 179 · see citing works
Distribution of prolactin‐responsive neurons in the mouse forebrain
Brown, R. S. E., Kokay, I. C., Herbison, A. E., & Grattan, D. R. (2009) · The Journal of Comparative Neurology · doi:10.1002/cne.22208 · Cited by 174 · see citing works
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Oswal, A., & Yeo, G. S. H. (2009) · Obesity · doi:10.1038/oby.2009.228 · Cited by 164 · see citing works
Farr, O. M., Tsoukas, M. A., & Mantzoros, C. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.07.004 · Cited by 146 · see citing works
Wada, N., Hirako, S., Takenoya, F., Kageyama, H., Okabe, M., & Shioda, S. (2014) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2014.09.002 · Cited by 145 · see citing works
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Self-citationYarandi, S., Hebbar, G., Sauer, C. G., Cole, C. R., & Ziegler, T. R. (2010) · Nutrition · doi:10.1016/j.nut.2010.07.004 · Cited by 132 · see citing works
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Emerging roles of JAK–STAT signaling pathways in adipocytes
Richard, A. J., & Stephens, J. M. (2011) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2011.03.007 · Cited by 108 · see citing works
Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia
Han, X., Ghaemi, M. S., Ando, K., Peterson, L. S., Ganio, E. A., Tsai, A. S., Gaudilliere, D. K., Stelzer, I. A., Einhaus, J. F., Bertrand, B., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01305 · Cited by 100 · see citing works
Role of Adipokines Signaling in the Modulation of T Cells Function
Procaccini, C., Rosa, V. D., Galgani, M., Carbone, F., Rocca, C. L., Formisano, L., & Matarese, G. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00332 · Cited by 99 · see citing works
Lee, J.-Y., Muenzberg, H., Gavrilova, O., Reed, J. A., Berryman, D., Villanueva, E. C., Louis, G. W., Leinninger, G. M., Bertuzzi, S., Seeley, R. J., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001639 · Cited by 90 · see citing works
Self-citationDiet-Induced Obesity and the Mechanism of Leptin Resistance
Engin, A. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_16 · Cited by 87 · see citing works
Central Regulation of Metabolism by Protein Tyrosine Phosphatases
Tsou, R. C., & Bence, K. K. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00192 · Cited by 85 · see citing works
Villanueva, E. C., Münzberg, H., Cota, D., Leshan, R. L., Kopp, K., Ishida-Takahashi, R., Jones, J. C., Fingar, D. C., Seeley, R. J., & Myers, M. G. (2009) · Endocrinology · doi:10.1210/en.2009-0642 · Cited by 81 · see citing works
Self-citationSun, Y., Yang, Y., Qin, Z., Cai, J., Guo, X.-M., Tang, Y., Wan, J., Su, D., & Liu, X. (2016) · Diabetes · doi:10.2337/db15-1193 · Cited by 78 · see citing works
Ladyman, S. R., Fieldwick, D., & Grattan, D. R. (2012) · Reproduction · doi:10.1530/rep-12-0112 · Cited by 77 · see citing works
Emerging role of leptin in rheumatoid arthritis
Tian, G., Liang, J.-N., Wang, Z.-Y., & Zhou, D. (2014) · Clinical & Experimental Immunology · doi:10.1111/cei.12372 · Cited by 70 · see citing works
Insulin Receptor Substrate 4 Couples the Leptin Receptor to Multiple Signaling Pathways
Wauman, J., de Smet, A.-S., Catteeuw, D., Belsham, D. D., & Tavernier, J. H. (2007) · Molecular Endocrinology · doi:10.1210/me.2007-0414 · Cited by 70 · see citing works
Roumaud, P., & Martin, L. J. (2015) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2015-0046 · Cited by 69 · see citing works
Jiang, L., You, J., Yu, X., Gonzalez, L., Yu, Y., Wang, Q. A., Yang, G., Li, W., Cai, L., & Liu, Y. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804589105 · Cited by 62 · see citing works
Patterson, C. M., Villanueva, E. C., Greenwald-Yarnell, M. L., Rajala, M. W., Gonzalez, I. E., Saini, N., Jones, J. C., & Myers, M. G. (2012) · Molecular Metabolism · doi:10.1016/j.molmet.2012.05.001 · Cited by 60 · see citing works
Self-citationObesity impairs lactation performance in mice by inducing prolactin resistance
Buonfiglio, D. D. C., Ramos-Lobo, A. M., Freitas, V. M., Zampieri, T. T., Nagaishi, V. S., Magalhães, M., Cipolla‐Neto, J., Cella, N., & Donato, J. (2016) · Scientific Reports · doi:10.1038/srep22421 · Cited by 60 · see citing works
LRb signals act within a distributed network of leptin‐responsive neurones to mediate leptin action
Leinninger, G. M., & Myers, M. G. (2008) · Acta Physiologica · doi:10.1111/j.1748-1716.2007.01784.x · Cited by 56 · see citing works
Self-citationErichsen, J. M., Fadel, J. R., & Reagan, L. P. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108877 · Cited by 56 · see citing works
Physiological Models of Leptin Resistance
Tups, A. (2009) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2009.01916.x · Cited by 54 · see citing works
López, H. S., Lanuza, E., Agustín‐Pavón, C., & Martínez‐Garciá, F. (2016) · Brain Structure and Function · doi:10.1007/s00429-016-1254-5 · Cited by 54 · see citing works
STAT3 activation by leptin receptor is essential for TNBC stem cell maintenance
Thiagarajan, P. S., Zheng, Q., Bhagrath, M., Mulkearns-Hubert, E. E., Myers, M. G., Lathia, J. D., & Reizes, O. (2017) · Endocrine Related Cancer · doi:10.1530/erc-16-0349 · Cited by 52 · see citing works
Self-citationLeptin in normal physiology and leptin resistance
Li, S., & Li, X. (2015) · 中国科学通报：英文版 · doi:10.1007/s11434-015-0951-4 · Cited by 51 · see citing works
Chemical and Hormonal Effects on STAT5b-Dependent Sexual Dimorphism of the Liver Transcriptome
Oshida, K., Waxman, D. J., & Corton, J. C. (2016) · PLoS ONE · doi:10.1371/journal.pone.0150284 · Cited by 50 · see citing works
Leptin Signaling in the Control of Metabolism and Appetite: Lessons from Animal Models
Barrios-Correa, A. A., Estrada, J. A., & Contreras, I. (2018) · Journal of Molecular Neuroscience · doi:10.1007/s12031-018-1185-0 · Cited by 51 · see citing works
Leptin signaling and leptin resistance
Liu, J., Lai, F., Hou, Y., & Zheng, R. (2022) · Medical Review · doi:10.1515/mr-2022-0017 · Cited by 55 · see citing works
Óvilo, C., Fernández, A., Fernández, A. I., Folch, J. M., Varona, L., Benítez, R., Núñez, Y., Rodríguez, C., & Silio, L. F. (2010) · Mammalian Genome · doi:10.1007/s00335-010-9307-1 · Cited by 48 · see citing works
Hindlet, P., Bado, A., Kamenický, P., Deloménie, C., Bourasset, F., Nazaret, C., Farinotti, R., & Buyse, M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m805564200 · Cited by 47 · see citing works
Signaling Pathways Induced by Leptin during Epithelial–Mesenchymal Transition in Breast Cancer
Olea‐Flores, M., Juárez-Cruz, J. C., Catalán, M. A. M., Padilla‐Benavides, T., & Navarro‐Tito, N. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113493 · Cited by 47 · see citing works
Ladyman, S. R., & Grattan, D. R. (2013) · JAK-STAT · doi:10.4161/jkst.23675 · Cited by 48 · see citing works
Leptin-Activity Modulators and Their Potential Pharmaceutical Applications
Greco, M., Santo, M. D., Comandé, A., Belsito, E. L., Andò, S., Liguori, A., & Leggio, A. (2021) · Biomolecules · doi:10.3390/biom11071045 · Cited by 46 · see citing works
Leptin, neuroinflammation and obesity
Dragano, N. R. V., Haddad-Tovolli, R., & Velloso, L. A. (2017) · Frontiers of hormone research · doi:10.1159/000452908 · Cited by 45 · see citing works
Evans, M. C., Lord, R. A., & Anderson, G. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179210 · Cited by 44 · see citing works
Protective Effects of Melatonin against Obesity‐Induced by Leptin Resistance
Suriyagandhi, V., & Nachiappan, V. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113598 · Cited by 44 · see citing works
Landry, D. A., Sormany, F., Haché, J., Roumaud, P., & Martin, L. J. (2017) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-017-3017-x · Cited by 43 · see citing works
Gove, M. E., Rhodes, D., Pini, M., van Baal, J. W. P. M., Sennello, J. A., Fayad, R., Cabay, R. J., Myers, M. G., & Fantuzzi, G. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0808508 · Cited by 42 · see citing works
Self-citationGlucose Enhances Leptin Signaling through Modulation of AMPK Activity
Su, H., Jiang, L., Carter‐Su, C., & Rui, L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031636 · Cited by 41 · see citing works
Transcriptional and physiological roles for STAT proteins in leptin action
Pan, W. W., Allison, M. B., Sabatini, P. V., Rupp, A. C., Adams, J. M., Patterson, C. M., Jones, J. C., Olson, D. P., & Myers, M. G. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.01.007 · Cited by 41 · see citing works
Self-citationMarwarha, G., Prasanthi, J. R. P., Schommer, J., Dasari, B., & Ghribi, O. (2011) · Molecular Neurodegeneration · doi:10.1186/1750-1326-6-41 · Cited by 40 · see citing works
New Actors Driving the Epithelial–Mesenchymal Transition in Cancer: The Role of Leptin
Olea‐Flores, M., Juárez-Cruz, J. C., Zuñiga‐Eulogio, M. D., Acosta, E., García-Rodríguez, E., Zacapala-Gómez, A. E., Catalán, M. A. M., Ortiz‐Ortiz, J., Ortuño‐Pineda, C., & Navarro‐Tito, N. (2020) · Biomolecules · doi:10.3390/biom10121676 · Cited by 39 · see citing works
Mancuso, P., Peters-Golden, M. L., Goel, D., Goldberg, J., Brock, T. G., Greenwald-Yarnell, M. L., & Myers, M. G. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001470 · Cited by 38 · see citing works
Self-citationDefining the Transcriptional Targets of Leptin Reveals a Role for Atf3 in Leptin Action
Allison, M. B., Pan, W. W., MacKenzie, A., Patterson, C. M., Shah, K., Barnes, T. M., Cheng, W., Rupp, A. C., Olson, D. P., & Myers, M. G. (2018) · Diabetes · doi:10.2337/db17-1395 · Cited by 38 · see citing works
Self-citationPharmacogenetics of Leptin in Antipsychotic-Associated Weight Gain and Obesity-Related Complications
Lee, A. K., & Bishop, J. R. (2011) · Pharmacogenomics · doi:10.2217/pgs.11.45 · Cited by 38 · see citing works
Pan, W. W., Adams, J. M., Allison, M. B., Patterson, C. M., Flak, J. N., Jones, J. C., Strohbehn, G. W., Trevaskis, J. L., Rhodes, C. J., Olson, D. P., et al. (2018) · Endocrinology · doi:10.1210/en.2017-03259 · Cited by 35 · see citing works
Self-citationLópez-Gambero, A. J., Rosell‐Valle, C., Vera, D. M., Navarro, J. A., Vargas, A., Rivera, P., Sanjuan, C., de Fonseca, F. R., & Suárez, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105365 · Cited by 35 · see citing works
Functional Consequences of the Human Leptin Receptor (LEPR) Q223R Transversion
Stratigopoulos, G., LeDuc, C. A., Matsuoka, N., Gutman, R., Rausch, R. N., Robertson, S., Myers, M. G., Chung, W. K., Chua, S. C., & Leibel, R. L. (2008) · Obesity · doi:10.1038/oby.2008.489 · Cited by 33 · see citing works
Self-citationIs sprint exercise a leptin signaling mimetic in human skeletal muscle?
Guerra, B., Olmedillas, H., Guadalupe‐Grau, A., Ponce‐González, J. G., Morales‐Álamo, D., Fuentes, T., Chapinal, E., Fernández‐Pérez, L., de Pablos-Velasco, P. L., Santana, A., et al. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00805.2010 · Cited by 34 · see citing works
Gastric Leptin and Tumorigenesis: Beyond Obesity
Inagaki‐Ohara, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112622 · Cited by 34 · see citing works
The Mechanism of Leptin Resistance in Obesity and Therapeutic Perspective
Engin, A. (2024) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-63657-8_16 · Cited by 37 · see citing works
Obesity and the Ageing Brain: Could Leptin Play a Role in Neurodegeneration?
Doherty, G. H. (2011) · Current Gerontology and Geriatrics Research · doi:10.1155/2011/708154 · Cited by 32 · see citing works
Jejunal Leptin-PI3K Signaling Lowers Glucose Production
Rasmussen, B. A., Breen, D. M., Duca, F. A., Côté, C. D., Zadeh‐Tahmasebi, M., Filippi, B., & Lam, T. K. T. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.11.014 · Cited by 32 · see citing works
Rivera, P., Ramírez-López, M. T., Vargas, A., Decara, J. M., Vázquez, M., Arco, R., de Heras, R. G., Argente, J., de Fonseca, F. R., Chowen, J. A., et al. (2018) · Acta Physiologica · doi:10.1111/apha.13244 · Cited by 31 · see citing works
Identification of STAT target genes in adipocytes
Zhao, P., & Stephens, J. M. (2013) · JAK-STAT · doi:10.4161/jkst.23092 · Cited by 31 · see citing works
You, J., Yu, Y., Jiang, L., Li, W., Yu, X., Gonzalez, L., Yang, G., Ke, Z., Li, W., Cai, L., et al. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.01307-09 · Cited by 31 · see citing works
Robertson, S., Ishida-Takahashi, R., Tawara, I., Hu, J., Patterson, C. M., Jones, J. C., Kulkarni, R. N., & Myers, M. G. (2010) · Diabetes · doi:10.2337/db09-1556 · Cited by 30 · see citing works
Self-citationBarnes, M. J., Primeaux, S. D., & Bray, G. A. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00030.2008 · Cited by 31 · see citing works
Mechanism of attenuation of leptin signaling under chronic ligand stimulation
Knobelspies, H., Zeidler, J., Hekerman, P., Bamberg‐Lemper, S., & Becker, W. (2010) · BMC Biochemistry · doi:10.1186/1471-2091-11-2 · Cited by 35 · see citing works
Cui, M. Y., Hu, C. K., Pelletier, C., Dziuba, A., Slupski, R. H., Li, C., & Denver, R. J. (2014) · Endocrinology · doi:10.1210/en.2014-1301 · Cited by 29 · see citing works
Brain STAT5 signaling and behavioral control
Furigo, I. C., Ramos-Lobo, A. M., Frazão, R., & Donato, J. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.04.019 · Cited by 29 · see citing works
PI3K signaling: A key pathway in the control of sympathetic traffic and arterial pressure by leptin
Harlan, S. M., & Rahmouni, K. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.03.004 · Cited by 29 · see citing works
Leptin Signaling and Action in Birds
Ohkubo, T., & Adachi, H. (2008) · The Journal of Poultry Science · doi:10.2141/jpsa.45.233 · Cited by 27 · see citing works
Mancuso, P., Myers, M. G., Goel, D., Serezani, C. H., O’Brien, E., Goldberg, J., Aronoff, D. M., & Peters-Golden, M. L. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200465 · Cited by 26 · see citing works
Self-citationThe role of leptin in central nervous system diseases
Li, X., Yan, H., Guo, Y., & Wang, D. (2016) · Neuroreport · doi:10.1097/wnr.0000000000000546 · Cited by 26 · see citing works
The hypothalamic ventral premammillary nucleus: A key site in leptin's regulation of reproduction.
Leshan, R., & Pfaff, D. (2014) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2014.08.008 · Cited by 28 · see citing works
Cardiovascular and Sympathetic Effects of Disrupting Tyrosine 985 of the Leptin Receptor
Harlan, S. M., Morgan, D. A., Dellsperger, D. J., Myers, M. G., Mark, A. L., & Rahmouni, K. (2011) · Hypertension · doi:10.1161/hypertensionaha.110.166538 · Cited by 24 · see citing works
Self-citationLiu, J., Yang, X., Yu, S., & Zheng, R. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-1286-1_7 · Cited by 24 · see citing works
Buntin, J. D., & Buntin, L. (2014) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2014.02.006 · Cited by 23 · see citing works
- Authors
- Gong, Y., Ishida-Takahashi, R., Villanueva, E. C., Fingar, D. C., Münzberg, H., & Myers, M. G.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Myers, Martin G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 282
- Issue
- 42
- Pages
- 31019-31027
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2065186264
- Cited by
- 173
- References
- 59
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 13 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 8 · 2016: 14 · 2015: 12 · 2014: 14 · 2013: 12 · 2012: 7
- FWCI
- 4.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk078135-03)
- National Cancer Institute (P30CA046592)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK20572, R01 DK57768, R01 DK78135, R01DK057768, R01-DK-56731, R01DK056731)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, STAT5, ribosomal protein S6, receptor tyrosine phosphorylation, STAT3, RSK, cap-dependent translation, ERK signaling, hypothalamic arcuate nucleus, energy homeostasis, neuroendocrine regulation
- MeSH terms
- Animals, Arcuate Nucleus of Hypothalamus, Cell Line, Energy Metabolism, Humans, Nerve Tissue Proteins, Phosphorylation, Protein Processing, Post-Translational, RNA Caps, Transcription, Genetic, Ribosomal Protein S6 Kinases, Protein Isoforms, Leptin, MAP Kinase Signaling System, Ribosomal Protein S6, Extracellular Signal-Regulated MAP Kinases, STAT3 Transcription Factor, STAT5 Transcription Factor, Mice, Receptors, Leptin
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