Critical role of STAT3 in leptin's metabolic actions
Open accessAbstract
Leptin has pleiotropic effects on glucose homeostasis and feeding behavior. Here, we validate the use of a cell-permeable phosphopeptide that blocks STAT3 activation in vivo. The combination of this biochemical approach with stereotaxic surgical techniques allowed us to pinpoint the contribution of hypothalamic STAT3 to the acute effects of leptin on food intake and glucose homeostasis. Leptin's ability to acutely reduce food intake critically depends on intact STAT3 signaling. Likewise, hypothalamic signaling of leptin through STAT3 is required for the acute effects of leptin on liver glucose fluxes. Lifelong obliteration of STAT3 signaling via the leptin receptor in mice (s/s mice) results in severe hepatic insulin resistance that is comparable to that observed in db/db mice, devoid of leptin receptor signaling. Our results demonstrate that the activation of the hypothalamic STAT3 pathway is an absolute requirement for the effects of leptin on food intake and hepatic glucose metabolism.
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The ability of hypothalamic leptin to regulate food intake, glucose metabolism and reproductive function requires intact STAT3 signaling.
“while the ability of hypothalamic leptin to regulate food intake, glucose metabolism and reproductive function requires intact STAT3 signaling”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [28]
Infusion of leptin directly into the mediobasal hypothalamus during a euglycemic-hyperinsulinemic clamp suppresses expression of key de novo lipogenic enzymes in white adipose tissue and activates lipolysis and suppresses free fatty acid uptake into this tissue.
“Infusion of leptin directly into the mediobasal hypothalamus during an euglycemic-hyperinsulinemic clamp suppressed the expression of key de novo lipogenic enzymes in WAT and also activated lipolysis and suppressed FFA uptake into this tissue (28).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [28]
The effects of leptin on adipose tissue metabolism are STAT3-independent and appear to involve hypothalamic PI3K and sympathetic nervous system outflow.
“these effects of leptin on adipose tissue metabolism are STAT3-independent, appearing instead to involve hypothalamic PI3K and SNS outflow (28).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [28]
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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
Leptin receptor signaling: pathways to leptin resistance
Wauman, J. (2011) · Frontiers in bioscience · doi:10.2741/3885 · Cited by 179 · see citing works
“Biochemical blockage of STAT3 activation has pinpointed the essential role of STAT3 for the acute effects of leptin on food intake and glucose homeostasis (119).”
BackgroundThe Leptin Receptor Complex: Heavier Than Expected?
Wauman, J., Zabeau, L., & Tavernier, J. H. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00030 · Cited by 178 · see citing works
German, J., Kim, F., Schwartz, G. J., Havel, P. J., Rhodes, C. J., Schwartz, M. W., & Morton, G. J. (2009) · Endocrinology · doi:10.1210/en.2009-0445 · Cited by 164 · see citing works
Oswal, A., & Yeo, G. S. H. (2009) · Obesity · doi:10.1038/oby.2009.228 · Cited by 164 · see citing works
Acute Humanin Therapy Attenuates Myocardial Ischemia and Reperfusion Injury in Mice
Muzumdar, R. H., Huffman, D. M., Calvert, J. W., Jha, S. K., Weinberg, Y., Cui, L., Nemkal, A., Atzmon, G., Klein, L., Gundewar, S., et al. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.205997 · Cited by 164 · see citing works
Human IL6 enhances leptin action in mice
Sadagurski, M., Norquay, L., Farhang, J., D’Aquino, K. E., Copps, K. D., & White, M. F. (2009) · Diabetologia · doi:10.1007/s00125-009-1580-8 · Cited by 161 · see citing works
“We investigated the STAT3 to SOCS3 signalling cascade in the hypothalamus of wild-type and hIL6 mice, where this pathway plays an important role in regulating expression of Pomc and Agrp [35].”
BackgroundLeptin brain entry via a tanycytic LepR–EGFR shuttle controls lipid metabolism and pancreas function
Duquenne, M., Folgueira, C., Bourouh, C., Millet, M., Silva, A. J., Clasadonte, J., Imbernón, M., Fernandois, D., Martínez‐Corral, I., Kusumakshi, S., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00432-5 · Cited by 161 · see citing works
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“For example, STAT-3 mediates the effect of leptin on food intake, hepatic glucose production, and gonadotropin secretion [15], whereas control of lipogenesis in adipose tissue, induction of arterial intima formation by leptin, increase of absorption of peptides, and proinflammatory effects of leptin in the colon and l…”
BackgroundThe pleiotropic roles of leptin in metabolism, immunity, and cancer
de Candia, P., Prattichizzo, F., Garavelli, S., Alviggi, C., Cava, A. L., & Matarese, G. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20191593 · Cited by 132 · see citing works
Vascular biology of metabolic syndrome
Vykoukal, D. M., & Davies, M. G. (2011) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2011.01.003 · Cited by 128 · see citing works
Transcriptional Basis for Rhythmic Control of Hunger and Metabolism within the AgRP Neuron
Cedernaes, J., Huang, W., Ramsey, K. M., Waldeck, N. J., Cheng, L., Marcheva, B., Omura, C., Kobayashi, Y., Peek, C. B., Levine, D. C., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.023 · Cited by 126 · see citing works
“043) in arcuate nucleus (Buettner et al., 2006) (Figure S4F).”
Neuronal regulation of homeostasis by nutrient sensing
Lam, T. K. T. (2010) · Nature Medicine · doi:10.1038/nm0410-392 · Cited by 125 · see citing works
Central insulin and leptin-mediated autonomic control of glucose homeostasis
Marino, J. S., Xu, Y., & Hill, J. W. (2011) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2011.03.001 · Cited by 123 · see citing works
Integrative neurobiology of energy homeostasis-neurocircuits, signals and mediators
Sánchez-Lasheras, C., Könner, A. C., & Brüning, J. C. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.08.002 · Cited by 120 · see citing works
“However, more recent studies on leptin signaling in the mediobasal hypothalamus in a model of induced STAT3 inactivation resulted in a strong reduction of gluconeogenesis after icv injection of leptin that was dependent on STAT3 activation [34].”
BackgroundDeletion of leptin signaling in vagal afferent neurons results in hyperphagia and obesity
de Lartigue, G., Ronveaux, C. C., & Raybould, H. E. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.06.003 · Cited by 117 · see citing works
“In the current study, we test the hypothesis that leptin resistance in VAN is an initiating factor in the development of hyperphagia and obesity.”
BackgroundHackl, M. T., Fürnsinn, C., Schuh, C. M., Krššák, M., Carli, F., Guerra, S., Freudenthaler, A., Baumgartner-Parzer, S. M., Helbich, T. H., Luger, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10684-1 · Cited by 117 · see citing works
Self-citationRing, L. E., & Zeltser, L. M. (2010) · Journal of Clinical Investigation · doi:10.1172/jci41985 · Cited by 115 · see citing works
Piper, M. L., Unger, E. K., Myers, M. G., & Xu, A. W. (2007) · Molecular Endocrinology · doi:10.1210/me.2007-0389 · Cited by 113 · see citing works
Self-citationCD36-Facilitated Fatty Acid Uptake Inhibits Leptin Production and Signaling in Adipose Tissue
Hajri, T., Hall, A. M., Jensen, D. R., Pietka, T. A., Drover, V. A., Tao, H., Eckel, R., & Abumrad, N. A. (2007) · Diabetes · doi:10.2337/db06-1699 · Cited by 111 · see citing works
“STAT3 phosphorylation (p-STAT3), a sensitive indicator of leptin activity (4,34,35) was 10-fold higher in CD36 / compared with wild-type tissue, whereas total STAT3 content was similar (Fig.”
BackgroundCNS Regulation of Glucose Homeostasis
Lam, C., Chari, M., & Lam, T. K. T. (2009) · Physiology · doi:10.1152/physiol.00003.2009 · Cited by 110 · see citing works
Engineered commensals for targeted nose-to-brain drug delivery
Shen, H., Aggarwal, N., Cui, B., Foo, G. W., He, Y., Srivastava, S. K., Li, S., Seah, M. Z. X., Wun, K. S., Ling, H., et al. (2025) · Cell · doi:10.1016/j.cell.2025.01.017 · Cited by 113 · see citing works
Role of AMP‐Activated Protein Kinase in the Control of Appetite
Kola, B. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01745.x · Cited by 109 · see citing works
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
Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake
Tan, H. L., Yin, L., Tan, Y., Ivanov, J., Plucińska, K., Ilanges, A., Herb, B. R., Wang, P., Kosse, C., Cohen, P., et al. (2024) · Nature · doi:10.1038/s41586-024-08108-2 · Cited by 106 · see citing works
“We found synchronized oIPSCs after light activation in approximately 81% of AGRP/NPY neurons (25 of 31) with a rapid onset and a latency of 5.12 ms (Fig.”
InfluentialAkt isoforms and glucose homeostasis – the leptin connection
Hay, N. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.09.003 · Cited by 99 · see citing works
“One possibility is that leptin suppresses hepatic expression of gluconeogenic genes through Stat3 activation via a mechanism independent of insulin and Akt in the liver.”
BackgroundTargeting the CNS to treat type 2 diabetes
Sandoval, D. A., Obici, S., & Seeley, R. J. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2874 · Cited by 100 · see citing works
“In support of this, pharmacological blockade of hypothalamic STAT3 signalling blocked leptin-induced anorexia and changes in hepatic glucose fluxes in rat”
BackgroundCôté, S. C., Gagné-Ouellet, V., Guay, S., Allard, C., Houde, A., Perron, P., Baillargeon, J., Gaudet, D., Guérin, R., Brisson, D., et al. (2016) · Clinical Epigenetics · doi:10.1186/s13148-016-0239-9 · Cited by 79 · see citing works
“binding sites that regulate leptin signaling, for example, at these two loci [51].”
BackgroundGhrelin and lipid metabolism: key partners in energy balance
Varela, L., Vazquez, M. J., Cordido, F., Nogueiras, R., Vidal‐Puig, A., Diéguez, C., & López, M. (2010) · Journal of Molecular Endocrinology · doi:10.1677/jme-10-0068 · Cited by 93 · see citing works
“…ghrelin on feeding and peripheral lipogenesis or a common mechanism for hormonal signals modulating both processes, such as leptin (Pocai et al. 2005b, Buettner et al. 2006, 2008), insulin (Obici et al. 2002a,b, Pocai et al. 2005a, Plum et al. 2006, Koch et al. 2008), melanocortins (Nogueiras et…”
Morton, G. J., Blevins, J. E., Kim, F., Matsen, M. E., & Figlewicz, D. P. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90865.2008 · Cited by 90 · see citing works
“A “knock-in” mouse model in which LepRb (a mutant for Tyr(1138)) replaces endogenous lepr to specifically disrupt lepr-STAT signaling is characterized by hyperphagia and obesity (3), whereas leptin’s ability to acutely reduce food intake depends on intact STAT3 signaling (9).”
BackgroundThe role of the endocannabinoid system in lipogenesis and fatty acid metabolism
Vettor, R., & Pagano, C. (2009) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2008.10.002 · Cited by 88 · see citing works
Amylin-Induced Central IL-6 Production Enhances Ventromedial Hypothalamic Leptin Signaling
Foll, C. L., Johnson, M. D., Dunn-Meynell, A. A., Boyle, C. N., Lutz, T. A., & Levin, B. E. (2014) · Diabetes · doi:10.2337/db14-0645 · Cited by 87 · see citing works
“We postulated that amylin interacts with leptin signaling by causing cells within the VMH to produce IL-6, which is known to phosphorylate STAT3, a common downstream mediator of leptin signaling (35,36), via its IL-6R complex.”
BackgroundHypothalamic AMP-Activated Protein Kinase Regulates Glucose Production
Yang, C. S., Lam, C. K. L., Chari, M., Cheung, G. W. C., Kokorovic, A., Gao, S., Leclerc, I., Rutter, G. A., & Lam, T. K. T. (2010) · Diabetes · doi:10.2337/db10-0221 · Cited by 86 · see citing works
Münzberg, H., Jobst, E. E., Bates, S. H., Jones, J. C., Villanueva, E. C., Leshan, R. L., Björnholm, M., Elmquist, J. K., Sleeman, M. W., Cowley, M. A., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3168-06.2007 · Cited by 86 · see citing works
“, 2006), as well as in the regulation of reproduction, growth, immune function, and glucose homeostasis (Bates et al., 2003, 2005; Dunn et al., 2005; Buettner et al., 2006).”
Self-citationIntranasal Leptin Relieves Sleep-disordered Breathing in Mice with Diet-induced Obesity
Berger, S., Pho, H., Curado, T. F., Bevans‐Fonti, S., Younas, H., Shin, M., Jun, J. C., Anokye‐Danso, F., Ahima, R. S., Enquist, L. W., et al. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201805-0879oc · Cited by 83 · see citing works
Peripheral cannabinoid-1 receptor blockade restores hypothalamic leptin signaling
Tam, J., Szanda, G., Drori, A., Liu, Z., Çınar, R., Kashiwaya, Y., Reitman, M. L., & Kunos, G. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.06.010 · Cited by 78 · see citing works
“This is compatible with the role of pSTAT3 signaling in the metabolic effects of endogenous leptin, as proposed previously [33,34].”
BackgroundRoman, E. A. F. R., Reis, D., Romanatto, T., Maimoni, D., Ferreira, E. A., Santos, G. A., Torsoni, A. S., Velloso, L. A., & Torsoni, M. A. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.08.007 · Cited by 71 · see citing works
Côté, C. D., Zadeh‐Tahmasebi, M., Rasmussen, B. A., Duca, F. A., & Lam, T. K. T. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.o114.556068 · Cited by 71 · see citing works
“Leptin binds to the hypothalamic Ob-Rb and activates downstream effectors STAT3 via Jak-2 (86, 87) and PI3K through phosphorylation of insulin receptor substrate (88) to regulate glucose homeostasis.”
BackgroundShort Term Voluntary Overfeeding Disrupts Brain Insulin Control of Adipose Tissue Lipolysis
Scherer, T., Lindtner, C., Zieliński, E., O’Hare, J., Filatova, N., & Buettner, C. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.307348 · Cited by 70 · see citing works
Self-citationThe subfornical organ: a central nervous system site for actions of circulating leptin
Smith, P., Chambers, A. P., Price, C. J., Ho, W., Hopf, C., Sharkey, K. A., & Ferguson, A. V. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90858.2008 · Cited by 70 · see citing works
Targeting Intermediary Metabolism in the Hypothalamus as a Mechanism to Regulate Appetite
Lopaschuk, G. D., Ussher, J. R., & Jaswal, J. S. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002428 · Cited by 68 · see citing works
“The STAT3 pathway has been shown to be necessary for leptin-induced hypophagia (Buettner et al., 2006) (section III.”
BackgroundInterleukin-17A increases leptin production in human bone marrow mesenchymal stem cells
Noh, M. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.12.010 · Cited by 68 · see citing works
Wu, D., Yang, M., Chen, Y., Jia, Y., Ma, Z. A., Boden, G. H., Li, L., & Yang, G. (2014) · Diabetes · doi:10.2337/db13-0899 · Cited by 66 · see citing works
Perinatal Maternal Fat Intake Affects Metabolism and Hippocampal Function in the Offspring
Walker, C., Naef, L., D’Asti, E., Long, H., Xu, Z., Moreau, A., & Azeddine, B. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1418.023 · Cited by 65 · see citing works
Toda, C., Shiuchi, T., Kageyama, H., Okamoto, S., Coutinho, E. A., Sato, T., Okamatsu‐Ogura, Y., Yokota, S., Takagi, K., Tang, L., et al. (2013) · Diabetes · doi:10.2337/db12-1629 · Cited by 63 · see citing works
“Furthermore, intracerebroventricular injection of a STAT3 inhibitor suppressed leptin-induced enhancement of insulin sensitivity in the liver, and abolishment of Ob-Rb–dependent STAT3 signaling (in s/smice) results in pronounced hepatic insulin resistance (32).”
BackgroundRegulation of lipid metabolism by energy availability: a role for the central nervous system
Nogueiras, R., López, M., & Diéguez, C. (2009) · Obesity Reviews · doi:10.1111/j.1467-789x.2009.00669.x · Cited by 62 · see citing works
“Interestingly, central leptin does not require signal transducer and activator of transcription 3 (STAT3) signalling for the control of adipose tissue metabolism, even though STAT3 is crucial for the ability of leptin to suppress hepatic glucose production and food intake (59).”
BackgroundAlmeida, S. M., Furtado, J., Mascarenhas, P., Ferraz, M. E., Ferreira, J. C., Monteiro, M. P., Vilanova, M., & Ferraz, F. P. (2018) · Endocrine · doi:10.1007/s12020-018-1587-3 · Cited by 61 · see citing works
Briançon, N., McNay, D. E. G., Maratos–Flier, E., & Flier, J. S. (2010) · Diabetes · doi:10.2337/db10-0481 · Cited by 60 · see citing works
“Interestingly, the Socs-3 gene is a target for signal transducer and activator of transcription (STAT) 3, which is a crucial mediator of leptin signaling (24).”
BackgroundEvidence for Central Regulation of Glucose Metabolism
Carey, M., Kehlenbrink, S., & Hawkins, M. A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.r113.506782 · Cited by 57 · see citing works
Al‐Khalaf, H. H., Al‐Harbi, B., Alsayed, A., Arafah, M., Tulbah, A. M., Jarman, A. T., Almohanna, F., & Aboussekhra, A. (2018) · Molecular and Cellular Biology · doi:10.1128/mcb.00332-18 · Cited by 58 · see citing works
“Interestingly, the levels of both basal and active forms of the AKT and STAT3 proteins, the downstream effectors of the IL-8 signaling (16), were higher in all (100%) CAAs than in TCAs (Fig.”
BackgroundSeoane‐Collazo, P., Martínez‐Sánchez, N., Milbank, E., & Contreras, C. (2020) · Nutrients · doi:10.3390/nu12020472 · Cited by 58 · 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
“…infertile and demonstrate decreased linear growth, s/s mice exhibit greatly improved glucose tolerance compared with db/db mice, retain relatively normal gonad function and demonstrate increased linear growth compared with wild-type animals (Bates et al. 2003, 2004, 2005, Buettner et al. 2006).”
BackgroundSelf-citationThe emerging role of lactate as a mediator of exercise-induced appetite suppression
McCarthy, S. F., Islam, H., & Hazell, T. J. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00256.2020 · Cited by 54 · see citing works
Control of T Cell Metabolism by Cytokines and Hormones
Bishop, E. L., Gudgeon, N. H., & Dimeloe, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.653605 · Cited by 53 · see citing works
Leptin Signaling Suppression in Macrophages Improves Immunometabolic Outcomes in Obesity
Monteiro, L. D. B., Prodonoff, J. S., de Aguiar, C. F., Corrêa‐da‐Silva, F., Castoldi, Â., Bakker, N. V. T., Davanzo, G. G., Castelucci, B. G., Pereira, J. A. D. S., Curtis, J. D., et al. (2022) · Diabetes · doi:10.2337/db21-0842 · Cited by 53 · see citing works
Foxc2 coordinates inflammation and browning of white adipose by leptin-STAT3-PRDM16 signal in mice
Gan, L., Liu, Z., Feng, F., Wu, T., Luo, D., Hu, C. Y., & Sun, C. (2017) · International Journal of Obesity · doi:10.1038/ijo.2017.208 · Cited by 52 · see citing works
Enhancement of Hypothalamic STAT3 Acetylation by Nuclear Receptor Nur77 Dictates Leptin Sensitivity
Chen, Y., Wu, R., Chen, H., Xiao, Q., Wang, W., He, J., Li, X., Yu, X., Li, L., Wang, P., et al. (2015) · Diabetes · doi:10.2337/db14-1206 · Cited by 51 · see citing works
“STAT3 is a critical component for leptin-activated signal pathways in the hypothalamus (22).”
BackgroundBless, E., Reddy, T., Acharya, K. D., Beltz, B., & Tetel, M. (2014) · Journal of neuroendocrinology · doi:10.1111/jne.12206 · Cited by 49 · see citing works
Changes in insulin sensitivity during leptin replacement therapy in leptin-deficient patients
Paz-Filho, G., Esposito, K. F., Hurwitz, B. E., Sharma, A. M., Dong, C., Andreev, V., Delibaşı, T., Erol, H. K., Ayala, A. R., Wong, M., et al. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90450.2008 · 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
Central signalling cross‐talk between insulin and leptin in glucose and energy homeostasis
Boucsein, A., Kamstra, K., & Tups, A. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12944 · Cited by 46 · see citing works
Ladyman, S. R., & Grattan, D. R. (2013) · JAK-STAT · doi:10.4161/jkst.23675 · Cited by 48 · see citing works
Li, M.-G., Ding, G., Chen, X., Lu, X.-P., Dong, L., Dong, M.-Y., Yang, X., Lu, X.-E., & Huang, H. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0978 · Cited by 47 · see citing works
Melanocortin control of energy balance: evidence from rodent models
Jonghe, B. C. D., Hayes, M. R., & Bence, K. K. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0707-5 · Cited by 47 · see citing works
Leptin in farm animals: where are we and where can we go?
Wylie, A. R. G. (2010) · animal · doi:10.1017/s1751731110001540 · Cited by 45 · see citing works
“As a class I cytokine receptor, ObR has no intrinsic kinase but instead uses Janus kinase (JAK) to phosphorylate STAT3, one of the family of Signal Transducers and Activators of Transcription, and an essential molecular component of the leptin signalling pathway (Buettner et al., 2006).”
BackgroundThree questions about leptin and immunity
Fantuzzi, G. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2008.10.007 · Cited by 45 · see citing works
“This same central pathway also regulates some of leptin-induced peripheral effects, such as hepatic insulin resistance ( Buettner et al., 2006 ).”
Johnson, C., Drummer, C., Virtue, A. T., Gao, T., Wu, S., Ibáñez-Hernández, M. Á., Singh, L., Wang, H., & Yang, X. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01297 · Cited by 45 · see citing works
“Moreover, T cell-mediated STAT3 promoted insulin resistance and obesity (Priceman et al., 2013) while leptin (satiety hormone) signaling relied on downstream STAT3 signaling (Buettner et al., 2006).”
BackgroundHypothalamic control of energy and glucose metabolism
Sisley, S. R., & Sandoval, D. A. (2011) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-011-9189-x · Cited by 44 · see citing works
“Genetic, viral or pharmacologic disruptions of hypothalamic STAT3 cause hyperphagia, obesity, and attenuate leptin-induced decreases in food intake [31, 32].”
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
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
“In another study in female rats, hypothalamic injection of a phosphopeptide inhibitor of STAT3 activation blocked the mid-cycle surge of luteinizing hormone (LH) that drives ovulation in females [39].”
BackgroundYang, M., Qiu, S., He, Y., Li, L., Wu, T., Ding, N., Li, F., Zhao, A. Z., & Yang, G. (2021) · Diabetologia · doi:10.1007/s00125-021-05384-9 · 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
“Although signaling through STAT3 mediates leptin’s effects on food intake, hepatic glucose production, and gonadotropin secretion [22], control of adipose tissue lipogenesis and arterial neointima formation by leptin is STAT3-independent [23, 24].”
BackgroundSelf-citationInsulin and glucagon signaling in the central nervous system
Filippi, B., Abraham, M. A., Yue, J. T. Y., & Lam, T. K. T. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-013-9258-4 · Cited by 42 · see citing works
“While multiple studies focusing on the CNS regulation of glucose homeostasis have confirmed that peripheral hormones such as insulin (see section above), leptin [114, 115], glucagon-like peptide-1 (GLP-1) [116] can signal in the brain to lower GP whereas central resistin [117] increases hepatic glucose production, ver…”
BackgroundLeptin resistance and desensitization of hypophagia during prolonged inflammatory challenge
Borges, B. C., Rorato, R. C., Avraham, Y., da Silva, L. E. C. M., de Castro, M., Vorobiav, L., Berry, E. M., Antunes-Rodrigues, J., & Elias, L. L. K. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00558.2010 · Cited by 41 · see citing works
Lee, Y.-H., Hsu, H.-C., Kao, P.-C., Shiao, Y., Yeh, S. H., Shie, F., Hsu, S.-M., Yeh, C.-W., Liu, H., Yang, S., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082333 · Cited by 37 · see citing works
“Hypothalamic leptin-receptor expressing neurons are mainly localized in the arcuate nucleus (ARC), ventromedial hypothalamus (VMH), and dorsomedial hypothalamus (DMH) in the mediobasal hypothalamus (MBH) [9,10].”
Background
- Authors
- Buettner, C., Pocai, A., Muse, E. D., Etgen, A. M., Myers, M. G., & Rossetti, L.
- Affiliations
- Albert Einstein College of Medicine (US)
- University of Michigan (US)
- Corresponding author
- Rossetti, Luciano
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 4
- Issue
- 1
- Pages
- 49-60
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3638026
- OpenAlex
- W2018642386
- Semantic Scholar
- c7871398d1131ca4a3e2b252cac205c9307d536d
- Cited by
- 228
- References
- 60
- Citations by year
- 2026: 3 · 2025: 17 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 17 · 2020: 11 · 2019: 10 · 2018: 14 · 2017: 10 · 2016: 9 · 2015: 9 · 2014: 14 · 2013: 19 · 2012: 10
- FWCI
- 5.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- National Institute of Mental Health (R37MH041414)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK045024, R01DK048321, R37DK048321, R01DK057768, P60DK020541)
- 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
- STAT3, leptin, hypothalamus, dietary intake, glucose homeostasis, hepatic insulin resistance, leptin receptor, hepatic glucose metabolism, db/db mice
- MeSH terms
- Animals, Appetite Regulation, Female, Glucose, Insulin Resistance, Luteinizing Hormone, Liver, Male, Mice, Inbred C57BL, Signal Transduction, Rats, Sprague-Dawley, Mice, Knockout, Leptin, STAT3 Transcription Factor, Mice, Rats
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 ›
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