Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity
Abstract
Leptin is an adipocyte-derived hormone that plays a key role in energy homeostasis, yet resistance to leptin is a feature of most cases of obesity in humans and rodents. In vitro analysis suggested that the suppressor of cytokine signaling-3 (Socs3) is a negative-feedback regulator of leptin signaling involved in leptin resistance. To determine the functional significance of Socs3 in vivo, we generated neural cell-specific SOCS3 conditional knockout mice using the Cre-loxP system. Compared to their wild-type littermates, Socs3-deficient mice showed enhanced leptin-induced hypothalamic Stat3 tyrosine phosphorylation as well as pro-opiomelanocortin (POMC) induction, and this resulted in a greater body weight loss and suppression of food intake. Moreover, the Socs3-deficient mice were resistant to high fat diet-induced weight gain and hyperleptinemia, and insulin-sensitivity was retained. These data indicate that Socs3 is a key regulator of diet-induced leptin as well as insulin resistance. Our study demonstrates the negative regulatory role of Socs3 in leptin signaling in vivo, and thus suppression of Socs3 in the brain is a potential therapy for leptin-resistance in obesity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
SOCS3 regulates leptin/pY-Jak2/pY-STAT3 signaling in the hypothalamus, causing leptin resistance.
“SOCS3 also regulates leptin/pY-Jak2/pY-STAT3 signaling in the hypothalamus, causing leptin resistance”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Mori et al., 2004
SOCS-3 induced via the IKKβ-NFκβ pathway during cellular inflammation can contribute to leptin resistance and has been implicated in the pathogenesis of diet-induced obesity.
“Since SOCS-3 can also be induced via the IKKβ-NFκβ pathway during cellular inflammation, this mechanism can contribute to leptin resistance in this setting (211) and has been implicated in the pathogenesis of diet-induced obesity (DIO) (87, 119, 211).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [119]
Neuron-specific SOCS-3 conditional knockout mice exhibit a similar phenotype of increased leptin sensitivity and protection from obesity.
“neuron-specific SOCS-3 conditional knockout mice exhibit a similar phenotype (119)”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [119]
Suppressor of cytokine signalling 3 deficiency enhances leptin signalling and reduces adiposity in mice maintained on a high-fat diet.
“Suppressor of cytokine signalling 3 (SOCS3) deficiency also enhanced leptin signalling and reduced adiposity in mice maintained on an HFD150.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [150]
SOCS3 deficiency increases leptin sensitivity and attenuates obesity development in mice fed a high fat diet.
“SOCS3 deficiency increases leptin sensitivity and attenuates obesity development in mice fed a high fat diet111.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [111]
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
Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans
Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., Ohannesian, J. P., Marco, C. C., McKee, L. J., Bauer, T. L., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602013340503 · Cited by 6,326 · 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
Role of Brain Insulin Receptor in Control of Body Weight and Reproduction
Brüning, J. C., Gautam, D., Burks, D. J., Gillette, J., Schubert, M., Orban, P. C., Klein, R., Krone, W., Müller-Wieland, D., & Kahn, C. R. (2000) · Science · doi:10.1126/science.289.5487.2122 · Cited by 2,235 · see citing works
Elchebly, M., Payette, P., Michaliszyn, E., Cromlish, W., Collins, S., Loy, A. L., Normandin, D., Cheng, A., Himms-Hagen, J., Chan, C.-C., et al. (1999) · Science · doi:10.1126/science.283.5407.1544 · Cited by 2,210 · see citing works
Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety
Tronche, F., Kellendonk, C., Kretz, O., Gass, P., Anlag, K., Orban, P. C., Bock, R., Klein, R., & Schütz, G. (1999) · Nature Genetics · doi:10.1038/12703 · Cited by 1,841 · see citing works
Ahima, R. S., & Flier, J. S. (2000) · Annual Review of Physiology · doi:10.1146/annurev.physiol.62.1.413 · Cited by 1,428 · see citing works
Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons
Woods, S. C., Lotter, E. C., McKay, L. D., & Porte, D. (1979) · Nature · doi:10.1038/282503a0 · Cited by 1,114 · see citing works
Cerebrospinal fluid leptin levels: Relationship to plasma levels and to adiposity in humans
Schwartz, M. W., Peskind, E., Raskind, M., Boyko, E. J., & Porte, D. (1996) · Nature Medicine · doi:10.1038/nm0596-589 · Cited by 1,014 · 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 1× · see citing works
“Stat3 is apparently essential for leptin regulation of energy balanc”
BackgroundSOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2
Rui, L., Yuan, M., Frantz, D., Shoelson, S., & White, M. F. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200444200 · Cited by 904 · see citing works
PTP1B 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
Defective 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
IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages
Yasukawa, H., Ohishi, M., Mori, H., Murakami, M., Chinen, T., Aki, D., Hanada, T., Takeda, K., Akira, S., Hoshijima, M., et al. (2003) · Nature Immunology · doi:10.1038/ni938 · Cited by 771 · see citing works
Self-citationSuppressors of cytokine signalling (SOCS) in the immune system
Alexander, W. S. (2002) · Nature reviews. Immunology · doi:10.1038/nri818 · Cited by 645 · see citing works
Zhu, Y., Romero‐Ortega, M. I., Ghosh, P., Ye, Z., Charnay, P., Rushing, E. J., Marth, J. D., & Parada, L. F. (2001) · Genes & Development · doi:10.1101/gad.862101 · Cited by 606 · see citing works
Negative Regulation of Cytokine Signaling Pathways
Yasukawa, H., Sasaki, A. T., & Yoshimura, A. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.143 · Cited by 596 · see citing works
Self-citationAttenuation of Leptin Action and Regulation of Obesity by Protein Tyrosine Phosphatase 1B
Cheng, A., Uetani, N., Simoncic, P. D., Chaubey, V. P., Lee-Loy, A., McGlade, C. J., Kennedy, B. P., & Tremblay, M. L. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00149-1 · Cited by 539 · 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
SOCS-3 Is an Insulin-induced Negative Regulator of Insulin Signaling
Emanuelli, B., Peraldi, P., Filloux, C., Sawka‐Verhelle, D., Hilton, D. J., & OBBERGHEN, E. V. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.21.15985 · Cited by 468 · see citing works
Regulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice
Thornton, J. E., Cheung, C. C., Clifton, D. K., & Steiner, R. A. (1997) · Endocrinology · doi:10.1210/endo.138.11.5651 · Cited by 437 · see citing works
Gao, Q., Wolfgang, M. J., Neschen, S., Morino, K., Horvath, T. L., Shulman, G. I., & Fu, X.-Y. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0303992101 · Cited by 385 · see citing works
Münzberg, H., Huo, L., Nillni, E. A., Hollenberg, A. N., & Bjørbæk, C. (2003) · Endocrinology · doi:10.1210/en.2002-221037 · Cited by 328 · see citing works
Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3
Roberts, A. W., Robb, L., Rakar, S., Hartley, L., Cluse, L., Nicola, N. A., Metcalf, D., Hilton, D. J., & Alexander, W. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161271798 · Cited by 300 · see citing works
Ebihara, K., Ogawa, Y., Masuzaki, H., Shintani, M., Miyanaga, F., Aizawa‐Abe, M., Hayashi, T., Hosoda, K., Inoue, G., Yoshimasa, Y., et al. (2001) · Diabetes · doi:10.2337/diabetes.50.6.1440 · Cited by 240 · 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
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
Kimura, A., Kinjyo, I., Matsumura, Y., Mori, H., Mashima, R., Harada, M., Chien, K. R., Yasukawa, H., & Yoshimura, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c300496200 · Cited by 119 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Inflammation, stress, and diabetes
Wellen, K. E., & Hotamisligil, G. S. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25102 · Cited by 4,143 · see citing works
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882 · see citing works
Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms
Hall, J. E., do Carmo, J. M., da Silva, A. A., Wang, Z., & Hall, M. E. (2015) · Circulation Research · doi:10.1161/circresaha.116.305697 · Cited by 1,360 · see citing works
Hypothalamic IKKβ/NF-κB and ER Stress Link Overnutrition to Energy Imbalance and Obesity
Zhang, X., Zhang, G., Zhang, H., Karin, M., Bai, H., & Cai, D. (2008) · Cell · doi:10.1016/j.cell.2008.07.043 · Cited by 1,350 · see citing works
De Souza, C. T., Araujo, E. P., Bordin, S., Ashimine, R., Zollner, R. L., Boschero, A. C., Saad, M. J. A., & Velloso, L. A. (2005) · Endocrinology · doi:10.1210/en.2004-1520 · Cited by 1,171 · see citing works
The Human Obesity Gene Map: The 2005 Update
Rankinen, T., Zuberi, A., Chagnon, Y. C., Weisnagel, S. J., Argyropoulos, G., Walts, B., Pérusse, L., & Bouchard, C. (2006) · Obesity · doi:10.1038/oby.2006.71 · Cited by 1,119 · see citing works
Leptin and Obesity: Role and clinical implication.
Obradovic, M., Sudar-Milovanovic, E., Soskic, S., Essack, M., Arya, S., Stewart, A. J., Gojobori, T., & Isenovic, E. R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.585887 · Cited by 1,121 · see citing works
Makki, K., Froguel, P., & Wolowczuk, I. (2013) · ISRN Inflammation · doi:10.1155/2013/139239 · Cited by 1,085 · 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
Astrocyte reactivity and reactive astrogliosis: costs and benefits
Pekny, M., & Pekna, M. (2014) · Physiological Reviews · doi:10.1152/physrev.00041.2013 · Cited by 934 · see citing works
Diabetes, Obesity, and the Brain
Schwartz, M. W., & Porte, D. (2005) · Science · doi:10.1126/science.1104344 · Cited by 841 · see citing works
Leptin and the endocrine control of energy balance
Friedman, J. M. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0095-y · Cited by 661 · see citing works
Obesity, kidney dysfunction and hypertension: mechanistic links
Hall, J. E., do Carmo, J. M., da Silva, A. A., Wang, Z., & Hall, M. E. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0145-4 · Cited by 654 · see citing works
Leptin in Human Physiology and Pathophysiology
Mantzoros, C. S., Magkos, F., Brinkoetter, M., Sienkiewicz, E., Dardeno, T. A., Kim, S.-Y., Hamnvik, O.-P. R., & Koniaris, A. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00315.2011 · Cited by 593 · see citing works
SOCS3, a Major Regulator of Infection and Inflammation
Carow, B., & Rottenberg, M. E. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00058 · Cited by 555 · see citing works
Diet-Induced Obesity Causes Severe but Reversible Leptin Resistance in Arcuate Melanocortin Neurons
Enriori, P. J., Evans, A. E., Sinnayah, P., Jobst, E. E., Tonelli-Lemos, L., Billes, S. K., Glavas, M. M., Grayson, B. E., Perello, M., Nillni, E. A., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.02.004 · Cited by 552 · see citing works
Molecular and anatomical determinants of central leptin resistance
Münzberg, H., & Myers, M. G. (2005) · Nature Neuroscience · doi:10.1038/nn1454 · Cited by 550 · see citing works
Leptin, Obesity, and Leptin Resistance: Where Are We 25 Years Later
Izquierdo, A. G., Crujeiras, A. B., Casanueva, F. F., & Carreira, M. C. (2019) · Nutrients · doi:10.3390/nu11112704 · Cited by 525 · see citing works
Kleinridders, A., Schenten, D., Könner, A. C., Belgardt, B. F., Mauer, J., Okamura, T., Wunderlich, F. T., Medzhitov, R., & Brüning, J. C. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.08.013 · Cited by 483 · see citing works
Leptin and Insulin Act on POMC Neurons to Promote the Browning of White Fat
Dodd, G. T., Decherf, S., Loh, K., Simonds, S. E., Wiede, F., Balland, E., Merry, T. L., Münzberg, H., Zhang, Z.-Y., Kahn, B. B., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.022 · Cited by 398 · see citing works
Hypothalamic CaMKK2 Contributes to the Regulation of Energy Balance
Anderson, K. A., Ribar, T. J., Lin, F., Noeldner, P. K., Green, M. F., Muehlbauer, M. J., Witters, L. A., Kemp, B. E., & Means, A. R. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.02.011 · Cited by 385 · see citing works
Hormonal regulation of food intake
Stanley, S., Wynne, K., McGowan, B., & Bloom, S. (2005) · Physiological Reviews · doi:10.1152/physrev.00015.2004 · Cited by 372 · see citing works
Neurobiology of Feeding and Energy Expenditure
Gao, Q., & Horvath, T. L. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094324 · Cited by 346 · see citing works
Leptin and the maintenance of elevated body weight
Pan, W. W., & Myers, M. G. (2018) · Nature reviews. Neuroscience · doi:10.1038/nrn.2017.168 · Cited by 344 · 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
“Overexpression of IGFBP2 also reduced blood glucose levels in models of leptin and insulin resistance/deficiency including agouti, DIO, and STZ-induced diabetic mice.”
BackgroundInfluentialBharadwaj, U., Kasembeli, M. M., Robinson, P., & Tweardy, D. J. (2020) · Pharmacological Reviews · doi:10.1124/pr.119.018440 · Cited by 314 · see citing works
“SOCS3 also regulates leptin/pY-Jak2/pYSTAT3 signaling in the hypothalamus, causing leptin resistance (Bjorbaek et al., 1999; Howard et al., 2004; Mori et al., 2004; de Lartigue et al., 2011; Metlakunta et al., 2011).”
BackgroundMinireview: Inflammation and Obesity Pathogenesis: The Hypothalamus Heats Up
Thaler, J. P., & Schwartz, M. W. (2010) · Endocrinology · doi:10.1210/en.2010-0336 · Cited by 313 · see citing works
Hyperleptinemia Is Required for the Development of Leptin Resistance
Knight, Z. A., Hannan, K. S., Greenberg, M. L., & Friedman, J. M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011376 · Cited by 311 · see citing works
Kershaw, N. J., Murphy, J. M., Liau, N. P. D., Varghese, L. N., Laktyushin, A., Whitlock, E. L., Lucet, I. S., Nicola, N. A., & Babon, J. J. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2519 · Cited by 301 · see citing works
The adipocyte as an active participant in energy balance and metabolism
Badman, M. K., & Flier, J. S. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.058 · Cited by 256 · see citing works
Neuroinflammation and neurodegeneration in overnutrition-induced diseases
Cai, D. (2013) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.11.003 · Cited by 256 · see citing works
Schéle, E., Grahnemo, L., Anesten, F., Hallén, A., Bäckhed, F., & Jansson, J.-O. (2013) · Endocrinology · doi:10.1210/en.2012-2151 · Cited by 209 · see citing works
Mice lacking inhibitory leptin receptor signals are lean with normal endocrine function
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. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30688 · Cited by 183 · see citing works
Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons
de Lartigue, G., Barbier de la Serre, C., Espero, E., Lee, J., & Raybould, H. E. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00056.2011 · Cited by 179 · see citing works
Reed, A. S., Unger, E. K., Olofsson, L. E., Piper, M. L., Myers, M. G., & Xu, A. W. (2010) · Diabetes · doi:10.2337/db09-1024 · Cited by 176 · see citing works
Babon, J. J., McManus, E. J., Yao, S., DeSouza, D. P., Mielke, L. A., Sprigg, N. S., Willson, T. A., Hilton, D. J., Nicola, N. A., Baca, M., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.024 · Cited by 163 · see citing works
Won, J. C., Jang, P., Namkoong, C., Koh, E. H., Kim, S. K., Park, J., Lee, K., & Kim, M. (2009) · Obesity · doi:10.1038/oby.2009.194 · Cited by 153 · see citing works
Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis
Rahmouni, K. (2014) · Hypertension · doi:10.1161/hypertensionaha.114.00920 · Cited by 150 · see citing works
Brain Adipocytokine Action and Metabolic Regulation
Ahima, R. S., Qi, Y., Singhal, N. S., Jackson, M. B., & Scherer, P. E. (2006) · Diabetes · doi:10.2337/db06-s018 · Cited by 150 · see citing works
Social Isolation Affects the Development of Obesity and Type 2 Diabetes in Mice
Nonogaki, K., Nozue, K., & Oka, Y. (2007) · Endocrinology · doi:10.1210/en.2007-0296 · Cited by 115 · see citing works
SOCS3 and its role in associated diseases
Yin, Y., Liu, W., & Dai, Y. (2015) · Human Immunology · doi:10.1016/j.humimm.2015.09.037 · Cited by 113 · see citing works
Schwartz, M. W., & Niswender, K. D. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0906 · Cited by 93 · 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
Feed-forward mechanisms: Addiction-like behavioral and molecular adaptations in overeating
Alsiö, J., Olszewski, P. K., Levine, A. S., & Schiöth, H. B. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2012.01.002 · 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
Neuroendocrine and metabolic effects of adipocyte-derived hormones
Jackson, M. B., & Ahima, R. S. (2006) · Clinical Science · doi:10.1042/cs20050243 · Cited by 68 · 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
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
Adipokines in healthy skeletal muscle and metabolic disease
Coles, C. A. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-27511-6_6 · Cited by 39 · see citing works
Control of metabolic and cardiovascular function by the leptin–brain melanocortin pathway
do Carmo, J. M., da Silva, A. A., Dubinion, J., Sessums, P. O., Ebaady, S. H., Wang, Z., & Hall, J. E. (2013) · IUBMB Life · doi:10.1002/iub.1187 · Cited by 36 · see citing works
do Carmo, J. M., da Silva, A. A., Freeman, J. N., Wang, Z., Moak, S. P., Hankins, M. W., Drummond, H. A., & Hall, J. E. (2018) · Hypertension · doi:10.1161/hypertensionaha.118.11127 · Cited by 11 · see citing works
Guo, H., Wang, Y., Zhao, Z., & Shao, X. (2015) · Scandinavian Journal of Immunology · doi:10.1111/sji.12257 · Cited by 9 · see citing works
- Authors
- Mori, H., Hanada, R., Hanada, T., Aki, D., Mashima, R., Nishinakamura, H., Torisu, T., Chien, K. R., Yasukawa, H., & Yoshimura, A.
- Affiliations
- Kyushu University (JP)
- Kurume University (JP)
- University of California San Diego (US)
- Corresponding author
- Yoshimura, Akihiko
- ORCID
- Venue
- Nature Medicine
- Published
- 2004-06-20
- Volume
- 10
- Issue
- 7
- Pages
- 739-743
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2042621509
- Cited by
- 651
- References
- 29
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 19 · 2023: 15 · 2022: 20 · 2021: 20 · 2020: 11 · 2019: 25 · 2018: 21 · 2017: 21 · 2016: 36 · 2015: 38 · 2014: 41 · 2013: 38 · 2012: 46
- FWCI
- 15.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Health Sciences Foundation
- 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 › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- SOCS3, leptin resistance, leptin signaling, diet-induced obesity, hypothalamus, STAT3 tyrosine phosphorylation, proopiomelanocortin, hyperleptinemia, insulin resistance, energy homeostasis, dietary intake, weight loss
- MeSH terms
- Suppressor of Cytokine Signaling 3 Protein, Animals, Brain Chemistry, Dietary Fats, DNA-Binding Proteins, Eating, Female, Insulin Resistance, Male, Obesity, Phosphorylation, Repressor Proteins, Transcription Factors, Weight Loss, Trans-Activators, Leptin, STAT3 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review