Mice lacking inhibitory leptin receptor signals are lean with normal endocrine function
Open accessAbstract
The adipose-derived hormone, leptin, acts via its receptor (LRb) to convey the status of body energy stores to the brain, decreasing feeding and potentiating neuroendocrine energy expenditure. The failure of high levels of leptin in most obese individuals to promote weight loss defines a state of diminished responsiveness to increased leptin, termed leptin resistance. Leptin stimulates the phosphorylation of several tyrosine residues on LRb to mediate leptin action. We homologously replaced LRb in mice with a receptor with a mutation in one of these sites (Tyr985) in order to examine its role in leptin action and signal attenuation in vivo. Mice homozygous for this mutation are neuroendocrinologically normal, but females demonstrate decreased feeding, decreased expression of orexigenic neuropeptides, protection from high-fat diet-induced obesity, and increased leptin sensitivity in a sex-biased manner. Thus, leptin activates autoinhibitory signals via LRb Tyr985 to attenuate the anti-adiposity effects of leptin, especially in females, potentially contributing to leptin insensitivity in obesity.
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Tyr985 attenuates leptin action in vivo, presumably by serving as the SOCS-3 binding site.
“These results support data from cultured cells (22) suggesting that Tyr985 attenuates leptin action in vivo, presumably by serving as the SOCS-3 binding site (24).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [24]
Mice with LepRb Tyr985 mutation (l/l) have a lean phenotype characterized by reduced food intake and adiposity and increased leptin sensitivity.
“mutation of Tyr985 in these (l/l) mice resulted in a lean phenotype characterized by reduced food intake and adiposity, and increased leptin sensitivity (24).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [24]
Mutation of LRb Tyr985 prevents SOCS-3 action on the leptin receptor and results in mice that display increased leptin sensitivity, are lean, and are resistant to diet-induced obesity.
“mutation of LRb Tyr985 prevents SOCS-3 action on the leptin receptor and thereby results in mice which display increased leptin sensitivity, are lean and are resistant to DIO (24).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [24]
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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
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
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
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
Leptin 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
Identification of SOCS-3 as a Potential Mediator of Central Leptin Resistance
Bjørbæk, C., Elmquist, J. K., Frantz, J. D., Shoelson, S. E., & Flier, J. S. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80062-3 · Cited by 1,014 · 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 · cited 20× · see citing works
“Although the effects of Tyr985 and other sensitizers of leptin signaling are most easily and commonly studied by examining the regulation of STAT3 signaling, the increased suppression of AgRP and NPY mRNA expression in the l/l animals also suggests the importance of Tyr985 in attenuating STAT3-independent signals, sin…”
BackgroundMethodInfluentialSelf-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
Self-citationPTP1B Regulates Leptin Signal Transduction In Vivo
Zabolotny, J. M., Bence, K. K., Stricker‐Krongrad, A., Haj, F. G., Wang, Y., Minokoshi, Y., Kim, Y., Elmquist, J. K., Tartaglia, L. A., Kahn, B. B., et al. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00148-x · Cited by 816 · 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-citationDhillon, H., Zigman, J. M., Ye, C., Lee, C. E., McGovern, R. A., Tang, V., Kenny, C. D., Christiansen, L. M., White, R. D., Edelstein, E. A., et al. (2006) · Neuron · doi:10.1016/j.neuron.2005.12.021 · Cited by 791 · 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-citationSelective 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
Mori, H., Hanada, R., Hanada, T., Aki, D., Mashima, R., Nishinakamura, H., Torisu, T., Chien, K. R., Yasukawa, H., & Yoshimura, A. (2004) · Nature Medicine · doi:10.1038/nm1071 · Cited by 651 · see citing works
Neuronal PTP1B regulates body weight, adiposity and leptin action
Bence, K. K., Delibegovic, M., Xue, B., Gorgun, C. Z., Hotamisligil, G. S., Neel, B. G., & Kahn, B. B. (2006) · Nature Medicine · doi:10.1038/nm1435 · Cited by 633 · 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
Gonadal Hormones Determine Sensitivity to Central Leptin and Insulin
Clegg, D. J., Brown, L. M., Woods, S. C., & Benoit, S. C. (2006) · Diabetes · doi:10.2337/diabetes.55.04.06.db05-1339 · Cited by 552 · 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-citationHoward, J. K., Cave, B. J., Oksanen, L. J., Tzameli, I., Bjørbæk, C., & Flier, J. S. (2004) · Nature Medicine · doi:10.1038/nm1072 · Cited by 490 · 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-citationCoppari, R., Ichinose, M., Lee, C. E., Pullen, A. E., Kenny, C. D., McGovern, R. A., Tang, V., Liu, S. M., Ludwig, T., Chua, S. C., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.004 · Cited by 457 · see citing works
Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake
Kitamura, T., Feng, Y., Kitamura, Y., Chua, S. C., Xu, A. W., Barsh, G. S., Rossetti, L., & Accili, D. (2006) · Nature Medicine · doi:10.1038/nm1392 · Cited by 449 · see citing works
Gao, Q., Mezei, G., Nie, Y., Rao, Y., Choi, C. S., Bechmann, I., Leranth, C., Toran-Allerand, D., Priest, C. A., Roberts, J. L., et al. (2007) · Nature Medicine · doi:10.1038/nm1525 · Cited by 416 · 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
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-citationCIS3/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
Diverse Biochemical Properties of Shp2 Mutants
Keilhack, H., David, F. S., McGregor, M. J., Cantley, L. C., & Neel, B. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504699200 · Cited by 299 · 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
Shp-2 Tyrosine Phosphatase: Signaling One Cell or Many
Feng, G.-S. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4668 · Cited by 285 · see citing works
Neuronal Shp2 tyrosine phosphatase controls energy balance and metabolism
Zhang, E. E., Chapeau, E. A., Hagihara, K., & Feng, G. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405041101 · Cited by 263 · 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 260 · see citing works
Self-citationThe role of leptin receptor signaling in feeding and neuroendocrine function
Bates, S. H., & Myers, M. G. (2003) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2003.10.003 · Cited by 239 · see citing works
Self-citationSuppressor of Cytokine Signaling 3 Is a Physiological Regulator of Adipocyte Insulin Signaling
Shi, H., Tzameli, I., Bjørbæk, C., & Flier, J. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403886200 · Cited by 223 · see citing works
Li, C., & Friedman, J. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.17.9677 · Cited by 177 · see citing works
Enhancing leptin response by preventing SH2-containing phosphatase 2 interaction with Ob receptor
Carpenter, L. R., Farruggella, T. J., Symes, A. J., Karow, M. L., Yancopoulos, G. D., & Stahl, N. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6061 · Cited by 175 · see citing works
Monogenic 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
Banks, W. A. (2004) · Peptides · doi:10.1016/j.peptides.2004.02.014 · Cited by 153 · see citing works
Dunn, S. L., Björnholm, M., Bates, S. H., Chen, Z., Seifert, M. M., & Myers, M. G. (2004) · Molecular Endocrinology · doi:10.1210/me.2004-0353 · Cited by 151 · see citing works
Self-citationTransgenic 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
Gender Differences in the Control of Energy Homeostasis
Woods, S. C., Gotoh, K., & Clegg, D. J. (2003) · Experimental Biology and Medicine · doi:10.1177/153537020322801012 · Cited by 144 · 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
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
盛, 裕. (2006) · Medical Entomology and Zoology · Cited by 58 · see citing works
Transcriptional Regulation of Agouti-Related Protein (Agrp) in Transgenic Mice
Kaelin, C. B., Xu, A. W., Lu, X., & Barsh, G. S. (2004) · Endocrinology · doi:10.1210/en.2004-0956 · Cited by 45 · see citing works
Pleiotropy of leptin receptor signalling is defined by distinct roles of the intracellular tyrosines
Hekerman, P., Zeidler, J., Bamberg‐Lemper, S., et al. (2004) · FEBS Journal · doi:10.1111/j.1742-4658.2004.04391.x · Cited by 38 · see citing works
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Galić, S., Oakhill, J. S., & Steinberg, G. R. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.08.018 · Cited by 1,597 · see citing works
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
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Izquierdo, A. G., Crujeiras, A. B., Casanueva, F. F., & Carreira, M. C. (2019) · Nutrients · doi:10.3390/nu11112704 · Cited by 525 · 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
Structure, production and signaling of leptin
Münzberg, H., & Morrison, C. D. (2014) · Metabolism · doi:10.1016/j.metabol.2014.09.010 · Cited by 455 · see citing works
Self-citationLeptin 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
Unsaturated fatty acids revert diet-induced hypothalamic inflammation in obesity
Cintra, D. E., Ropelle, E. R., Moraes, J. C., Pauli, J. R., Morari, J., de Souza, C. T., Grimaldi, R., Stahl, M., Carvalheira, J. B., Saad, M. J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030571 · Cited by 381 · see citing works
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BackgroundResultInfluentialHyperleptinemia Is Required for the Development of Leptin Resistance
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20 YEARS OF LEPTIN: Role of leptin in human reproductive disorders
Chou, S. H.-H., & Mantzoros, C. S. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0245 · Cited by 107 · see citing works
Pedroso, J. A. B., Buonfiglio, D. D. C., Cardinali, L. I., Furigo, I. C., Ramos-Lobo, A. M., Tirapegui, J., Elias, C. F., & Donato, J. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.06.001 · Cited by 102 · see citing works
MECHANISMS IN ENDOCRINOLOGY: The endocrine role of the skeleton: background and clinical evidence
Theiler‐Schwetz, V., Pieber, T. R., & Obermayer-Pietsch, B. M. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0030 · Cited by 102 · see citing works
Leptin-Signaling Pathways and Leptin Resistance
Münzberg, H. (2009) · Forum of nutrition/Bibliotheca Nutritio et dieta · doi:10.1159/000264400 · Cited by 100 · see citing works
Self-citationArteaga‐Solis, E., Zee, T., Emala, C. W., Vinson, C., Wess, J., & Karsenty, G. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.004 · Cited by 97 · see citing works
Functional Implications of Limited Leptin Receptor and Ghrelin Receptor Coexpression in the Brain
Perelló, M., Scott, M. M., Sakata, I., Lee, C. E., Chuang, J., Osborne-Lawrence, S., Rovinsky, S. A., Elmquist, J., & Zigman, J. (2012) · The Journal of comparative neurology · doi:10.1002/cne.22690 · Cited by 91 · see citing works
Leptin resensitisation: a reversion of leptin-resistant states
Andreoli, M. F., Donato, J., Çakır, I., & Perelló, M. (2019) · Journal of Endocrinology · doi:10.1530/joe-18-0606 · Cited by 95 · see citing works
Leptin Stimulates Both JAK2-dependent and JAK2-independent Signaling Pathways
Jiang, L., Li, Z., & Rui, L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805545200 · Cited by 94 · see citing works
Molière, S., Jaulin, A., Tomasetto, C., & Dali‐Youcef, N. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310649 · Cited by 93 · see citing works
Modulation of Leptin Resistance by Protein Tyrosine Phosphatases
St‐Pierre, J., & Tremblay, M. L. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.02.004 · Cited by 88 · see citing works
Vagal control of satiety and hormonal regulation of appetite
Owyang, C., & Heldsinger, A. (2011) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm.2011.17.4.338 · 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
Central Leptin Receptor Action and Resistance in Obesity
Bjørbæk, C. (2009) · Journal of Investigative Medicine · doi:10.2310/jim.0b013e3181bb0d49 · Cited by 86 · see citing works
Leptin Induces Hippocampal Synaptogenesis via CREB-Regulated MicroRNA-132 Suppression of p250GAP
Dhar, M., Zhu, M., Impey, S., Lambert, T. J., Bland, T., Karatsoreos, I. N., Nakazawa, T., Appleyard, S. M., & Wayman, G. A. (2014) · Molecular Endocrinology · doi:10.1210/me.2013-1332 · Cited by 82 · 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-citationMorrison, C. D., Huypens, P., Stewart, L. K., & Gettys, T. W. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.09.005 · Cited by 80 · see citing works
Tanida, M., Yamamoto, N., Morgan, D. A., Kurata, Y., Shibamoto, T., & Rahmouni, K. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.1828-14.2015 · Cited by 80 · see citing works
Bone Remodeling and Energy Metabolism: New Perspectives
de Paula, F. J. A., & Rosen, C. J. (2013) · Bone Research · doi:10.4248/br201301005 · Cited by 79 · see citing works
Structural insights into the mechanism of leptin receptor activation
Saxton, R. A., Caveney, N. A., Moya-Garzón, M. D., Householder, K. D., Rodriguez, G. E., Burdsall, K. A., Long, J. Z., & García, K. C. (2023) · Nature Communications · doi:10.1038/s41467-023-37169-6 · Cited by 81 · see citing works
Development of Diabesity in Mice with Neuronal Deletion of Shp2 Tyrosine Phosphatase
Krajewska, M., Banares, S., Zhang, E. E., Huang, X., Scadeng, M., Jhala, U. S., Feng, G.-S., & Krajewski, S. (2008) · The American Journal of Pathology · doi:10.2353/ajpath.2008.070594 · Cited by 72 · see citing works
Leptin receptor modulation of adiposity and fertility
Israel, D. D., & Chua, S. C. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2009.07.004 · Cited by 72 · see citing works
Wang, Y., Wan, R., & Hu, C. (2023) · Molecular Medicine · doi:10.1186/s10020-023-00702-w · Cited by 71 · see citing works
Tsou, R. C., Zimmer, D. J., Jonghe, B. C. D., & Bence, K. K. (2012) · Endocrinology · doi:10.1210/en.2012-1548 · Cited by 70 · see citing works
New Pharmacological Perspectives for the Leptin Receptor in the Treatment of Obesity
Roujeau, C., Jockers, R., & Dam, J. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00167 · Cited by 70 · 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
Townsend, K. L., Lorenzi, M. M., & Widmaier, E. P. (2008) · Endocrine · doi:10.1007/s12020-008-9070-1 · Cited by 61 · 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-citationAn Osteoblast‐dependent Mechanism Contributes to the Leptin Regulation of Insulin Secretion
Hinoi, E., Gao, N., Jung, D. Y., Yadav, V. K., Yoshizawa, T., Kajimura, D., Myers, M. G., Chua, S. C., Wang, Q., Kim, J. K., et al. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05061.x · Cited by 59 · see citing works
Self-citationSeoane‐Collazo, P., Martínez‐Sánchez, N., Milbank, E., & Contreras, C. (2020) · Nutrients · doi:10.3390/nu12020472 · Cited by 58 · see citing works
Münzberg, H. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.04.020 · Cited by 57 · see citing works
Self-citationNeuroendocrine Regulation of Metabolism
Cornejo, M. P., Hentges, S. T., Maliqueo, M. A., Coirini, H., Becú‐Villalobos, D., & Elias, C. F. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12395 · Cited by 57 · 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-citationPhenotypic effects of an induced mutation of the ObRa isoform of the leptin receptor
Li, Z., Ceccarini, G., Eisenstein, M., Tan, K., & Friedman, J. M. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.07.007 · Cited by 55 · see citing works
Co-dependence of bone and energy metabolisms
Wei, J., & Ducy, P. F. (2010) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2010.05.021 · Cited by 53 · see citing works
Palanivel, R., Fullerton, M. D., Galić, S., Honeyman, J. E., Hewitt, K., Jørgensen, S. B., & Steinberg, G. R. (2012) · Diabetologia · doi:10.1007/s00125-012-2665-3 · Cited by 51 · see citing works
Kamitakahara, A. K., Bouyer, K., Wang, C.-Y., & Simerly, R. B. (2017) · The Journal of Comparative Neurology · doi:10.1002/cne.24327 · Cited by 51 · see citing works
Leptin Keeps Working, Even in Obesity
Myers, M. G. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.017 · Cited by 51 · see citing works
Self-citationCellular Insulin Resistance Disrupts Leptin-Mediated Control of Neuronal Signaling and Transcription
Nazarians-Armavil, A., Menchella, J. A., & Belsham, D. D. (2013) · Molecular Endocrinology · doi:10.1210/me.2012-1338 · Cited by 47 · see citing works
Towards a serotonin-dependent leptin roadmap in the brain
Oury, F., & Karsenty, G. (2011) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2011.04.006 · Cited by 49 · see citing works
Leptin resistance and the response to positive energy balance
Morrison, C. D. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.04.009 · Cited by 49 · see citing works
Heldsinger, A. A., Grabauskas, G., Song, I., & Owyang, C. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.198945 · Cited by 44 · see citing works
Nestor, C. C., Kelly, M. J., & Rønnekleiv, O. K. (2013) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2013-0050 · Cited by 46 · see citing works
Li, Y., Wu, X., Zhou, S.-Y., & Owyang, C. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00356.2010 · Cited by 43 · see citing works
RetractedDetermination of the half-life of circulating leptin in the mouse
Burnett, L. C., Skowronski, A. A., Rausch, R., LeDuc, C. A., & Leibel, R. L. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.238 · Cited by 40 · see citing works
Relationships between Bone Turnover and Energy Metabolism
Fernandes, T., Gonçalves, L. M. L., & Brito, J. (2017) · Journal of Diabetes Research · doi:10.1155/2017/9021314 · 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-citationRole of the adipocyte-derived hormone leptin in reproductive control
García-Galiano, D., Allen, S. J., & Elias, C. F. (2014) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2014-0017 · Cited by 40 · see citing works
García-Galiano, D., Borges, B. C., Donato, J., Allen, S. J., Bellefontaine, N., Wang, M., Zhao, J. J., Kozloff, K. M., Hill, J. W., & Elias, C. F. (2017) · JCI Insight · doi:10.1172/jci.insight.96728 · Cited by 39 · see citing works
Drug targeting of leptin resistance
Santoro, A. N., Raso, G. M., & Meli, R. (2015) · Life Sciences · doi:10.1016/j.lfs.2015.05.012 · Cited by 41 · see citing works
Defining 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-citationZoledronic acid inhibits macrophage SOCS3 expression and enhances cytokine production
Scheller, E. L., Hankenson, K. D., Reuben, J. S., & Krebsbach, P. H. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.23267 · Cited by 36 · see citing works
Leptin Function and Regulation
Zhang, Y., & Chua, S. C. (2018) · Comprehensive physiology · doi:10.1002/j.2040-4603.2018.tb00002.x · Cited by 35 · see citing works
CNTF: a target therapeutic for obesity-related metabolic disease?
Matthews, V. B., & Febbraio, M. A. (2008) · Journal of Molecular Medicine · doi:10.1007/s00109-007-0286-y · Cited by 35 · 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-citationFunctional 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-citationInteraction of glucose sensing and leptin action in the brain
Li, R. J. W., Zhang, S., & Lam, T. K. T. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101011 · Cited by 34 · 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-citationHistory and future of leptin: Discovery, regulation and signaling
Münzberg, H., Heymsfield, S. B., Berthoud, H., & Morrison, C. D. (2024) · Metabolism · doi:10.1016/j.metabol.2024.156026 · Cited by 36 · see citing works
Self-citationMechanism 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
- Authors
- Björnholm, M., Münzberg, H., Leshan, R. L., Villanueva, E. C., Bates, S. H., Louis, G. W., Jones, J. C., Ishida-Takahashi, R., Bjørbaek, C., & Myers, M. G.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Myers, Martin G.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-05-01
- Volume
- 117
- Issue
- 5
- Pages
- 1354-1360
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1838925
- OpenAlex
- W2109717216
- Cited by
- 183
- References
- 48
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 3 · 2021: 3 · 2020: 11 · 2019: 7 · 2018: 8 · 2017: 13 · 2016: 3 · 2015: 8 · 2014: 17 · 2013: 16 · 2012: 17
- FWCI
- 7.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Svenska Sällskapet för Medicinsk Forskning
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK56731, R37DK056731, DK 57768, R01DK057768, R01DK056731)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- leptin, leptin receptor, leptin resistance, obesity, high-fat diet-induced obesity, feeding behavior, orexigenic peptides, sex differences, neuroendocrine regulation, energy homeostasis
- MeSH terms
- Animals, Endocrine System, Female, Male, Mice, Inbred C57BL, Obesity, Receptors, Cell Surface, Sensitivity and Specificity, Sex Factors, Thinness, Tyrosine, Signal Transduction, Amino Acid Substitution, Leptin, Mice, Receptors, Leptin
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