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STAT3 signalling is required for leptin regulation of energy balance but not reproduction
Abstract
Secretion of leptin from adipocytes communicates body energy status to the brain by activating the leptin receptor long form (LRb). LRb regulates energy homeostasis and neuroendocrine function; the absence of LRb in db/db mice results in obesity, impaired growth, infertility and diabetes. Tyr 1138 of LRb mediates activation of the transcription factor STAT3 during leptin action. To investigate the contribution of STAT3 signalling to leptin action in vivo, we replaced the gene encoding the leptin receptor (lepr) in mice with an allele coding for a replacement of Tyr 1138 in LRb with a serine residue (lepr(S1138)) that specifically disrupts the LRb-STAT3 signal. Here we show that, like db/db mice, lepr(S1138) homozygotes (s/s) are hyperphagic and obese. However, whereas db/db mice are infertile, short and diabetic, s/s mice are fertile, long and less hyperglycaemic. Furthermore, hypothalamic expression of neuropeptide Y (NPY) is elevated in db/db mice but not s/s mice, whereas the hypothalamic melanocortin system is suppressed in both db/db and s/s mice. LRb-STAT3 signalling thus mediates the effects of leptin on melanocortin production and body energy homeostasis, whereas distinct LRb signals regulate NPY and the control of fertility, growth and glucose homeostasis.
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“Recent evidence from transgenic animal models suggests that, in addition to the STAT3 signaling system, a distinct and parallel signal transduction pathway exists that regulates hypothalamic neuropeptide Y (NPY) and controls fertility, most likely through activation of extracellular signal-related kinase (ERK) and PI3K kinase (55).”
From The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men (2003) · cites this paper as [55]
In the citing paper
“Mice with homozygous knock-in substitution of LepRb tyrosine residue Tyr1138”
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 Bates et al., 2003
In the citing paper
“Mice bearing a mutant LepRb gene in which Tyr1138 is replaced by a serine residue (s/s mice) are unable to recruit STAT3 and are characterized by hyperphagia, obesity (14) and reduced energy expenditure (12)”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [14]
In the citing paper
“suggesting that the Tyr1138 →STAT3 pathway plays a crucial role in the regulation of regulation of energy homeostasis (12, 14).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [14]
In the citing paper
“However, the phenotype of these s/s mice does not completely mimic that of either ob/ob or db/db mice with respect to glucose metabolism, immune function or reproduction (13, 14), implying that other LepRb signals must also contribute to leptin action.”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [14]
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Gong, N., Jönsson, E., & Björnsson, B. T. (2015) · Journal of Molecular Endocrinology · doi:10.1530/jme-15-0279 · Cited by 49
Neuronal Rap1 Regulates Energy Balance, Glucose Homeostasis, and Leptin Actions
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“Further, cellular leptin sensitivity, as demonstrated by leptininduced phosphorylation of STAT3, a marker of activated leptin signaling (Bates et al., 2003; Gao et al., 2004; Metlakunta et al., 2008; Vaisse et al., 1996), was significantly enhanced in Rap1ΔCNS mice but absent in controls under HFD condition (Figure 4C…”
BackgroundLeptin 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 54
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“protein tyrosine phosphatase 2), MAPK (mitogen-activated protein kinase), JAK2 (Janus kinase 2) STAT3 (signal transducer and activator of transcription 3), AMPK (5′ adenosine monophosphate activated protein kinase) ACC (acetyl-CoA carboxylase), IRS (insulin receptor substrate), and P13 K (phosphatidylinositol 3-kinase…”
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“However, the role of neuronal STAT3 signaling on reproduction is leptin receptor independent (Bates et al., 2003); therefore, STAT3 is mediating nonleptinergic signals in the brain to impact reproductive function.”
Wu, S., Wang, Y., Ning, Y., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041035 · Cited by 47
“Numerous findings [14,15,38,39] suggest that STAT3 influences muscle and adipose tissue growth.”
BackgroundSelf-citationMetabolic control of puberty: 60 years in the footsteps of Kennedy and Mitra’s seminal work
Anderson, G. M., Hill, J. W., Kaiser, U. B., Navarro, V. M., Ong, K. K., Perry, J. R. B., Prévot, V., Tena‐Sempere, M., & Elias, C. F. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00919-z · Cited by 55
“In LepRb–STAT3 knockout mice 168,169 , or mice with a mutated LepRb that precludes STAT3 phosphorylation 170 , puberty onset and oestrous cycles are normal despite moderate obesity.”
Hosoi, T., Yamaguchi, R., Noji, K., Matsuo, S., Baba, S., Toyoda, K., Suezawa, T., Kayano, T., Tanaka, S., & Ozawa, K. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201303227 · Cited by 48
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“For this purpose, we assessed the capacity of leptin to induce the phosphorylation of STAT3 (pSTAT3), which depends on the long LepR isoform (Bates et al., 2003).”
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Dopytalska, K., Baranowska-Bik, A., Roszkiewicz, M., Bik, W., & Walecka, I. (2020) · Lipids in Health and Disease · doi:10.1186/s12944-020-01391-8 · Cited by 47
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“Bates et al. (2003) developed the s/s mouse, in which the leptin receptor does not contain the Y1138 phosphorylation site that is required for leptin-induced STAT3 phosphorylation.26 Due to the disrupted leptin receptor-STAT3 signaling, this mouse is hyperphagic and obese.4 Another mouse generated…”
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“The mTOR kinase also phosphorylates the signal transducer and activator of transcription 3, a transcription factor critically implicated in the actions of leptin on energy balance regulation((31)).”
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“STAT3 is activated downstream of leptin signaling, and is a critical signaling molecule which promotes many of the physiological effects of leptin [67-69].”
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“Leptin is an adipokine, a cytokine-like molecule produced by adipose tissue, which regulates appetite through JAK/STAT signalling of the hypothalamus in the setting of changes in adipose levels.(10,11) As rLIF induces cachexia-associated adipose loss, the reduction of adipose leptin compensates for rLIF’s anorexic eff…”
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“These results suggested that PI3K in POMC neurons exclusively mediate the acute anorexigenic effects of leptin, while the long-term effects of leptin to regulate energy expenditure and glucose balance may be mediated by the other prevalent signaling pathways [57,61–63].”
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Can faulty antennae increase adiposity? The link between cilia proteins and obesity
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“In the hypothalamus, binding of leptin to the leptin receptor isoform LRb causes phosphorylation of signal transducer and activator of transcription-3 (STAT3), which then activates POMC transcription (Bates et al. 2003).”
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“Bates et al. (2003) even showed that mice with disrupted LEPRb-STAT3 signalling were obese yet fertile.”
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“Given the previous finding that LepRb-mediated STAT3 signalling only appears to be critically required for the regulation of metabolic function [32], it seems other activators of STAT3 signalling in non-LepRb cells must be able to compensate for and thus safeguard reproductive function in the absence of LepRb-STAT3 si…”
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“In addition, SRC1 is also shown to interact with signal transducer and activator of trascription-3 (41), which is essential to mediate the antiobesity effects of leptin (42).”
BackgroundClusterin/ApoJ enhances central leptin signaling through Lrp2‐mediated endocytosis
Byun, K., Gil, S. Y., NamKoong, C., Youn, B., Huang, H., Shin, M., Kang, G. M., Kim, H., Lee, B., Kim, Y., et al. (2014) · EMBO Reports · doi:10.15252/embr.201338317 · Cited by 46
“Replacement of amino acid (Tyr1138 to Ser1138) in the long form leptin receptor (Leprb) that is critical for Stat3 activation caused severe obese phenotype as seen in Leprb-deficient mice [3].”
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 44
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“Thus, the relevant role of STAT3 in the effect of leptin in food intake has recently been demonstrated [40].”
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The central melanocortin system and human obesity
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“Among these, the Janus kinase 2 (Jak2)–signal transducer and activator of transcription 3 (Stat3) pathway represents the most critical one to feeding control (Bates et al., 2003; Baldini and Phelan, 2019).”
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“This step is required for STAT3 binding and activation, and the latter pathway has been found to be responsible for most of the biological effects of leptin within the central nervous system (20).”
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“Because Ob-Rb is the only isoform capable of activating all known transduction pathways in vivo attributed to leptin (Bates et al., 2003; Myers, 2004), our data indicate that the hypothalamus is the major site of leptin action in cattle as is the case in rodents (Ahima and Flier, 2000; Myers, 2004).”
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“[19,20].”
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“In fasted, lean animals the majority of circulating leptin is bound and this correlates with a minimal pSTAT3 signal in arcuate LepRb neurons at fasting (31).”
BackgroundIntegration of Circadian and Metabolic Control of Reproductive Function
Evans, M. C., & Anderson, G. M. (2018) · Endocrinology · doi:10.1210/en.2018-00691 · Cited by 41
Transcriptional and physiological roles for STAT proteins in leptin action
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Self-citationShin, S., You, I., Jeong, M., Bae, Y., Wang, X., Cawley, M. L., Han, A., & Lim, B. K. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01208-0 · Cited by 42
Shintani, T., Higashi, S., Suzuki, R., Takeuchi, Y., Ikaga, R., Yamazaki, T., Kobayashi, K., & Noda, M. (2017) · Scientific Reports · doi:10.1038/s41598-017-12070-7 · Cited by 40
Maffei, M., & Giordano, A. (2021) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09636-2 · Cited by 46
“Activation of the JAK2-STAT3 pathway in the hypothalamic neurons is essential for leptin to exert its full metabolic effect, as demonstrated by the hyperphagic and obese phenotypes found in mice where LepRb mutations at tyrosine 1138 prevent STAT3 activation [34] and in those lacking STAT3 in LepRb-bearing neurons [35…”
BackgroundRole of leptin in regulating appetite, neuroendocrine function, and bone remodeling
Cohen, M. M. (2006) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31099 · Cited by 42
Jhun, J. Y., Moon, S., Yoon, B. Y., Byun, J. K., Kim, E., Yang, E. J., Ju, J. H., Hong, Y. S., Min, J. K., Park, S. H., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078843 · Cited by 38
“STAT3 signaling is also required for leptin regulation of energy [33].”
BackgroundRole 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
“Nonetheless, mice with a selective lack of leptin-induced STAT3 signaling in LepRb-expressing cells showed an obese phenotype because of a hyperphagic state associated with a decrease in energy expenditure [78].”
BackgroundGarcía-Galiano, D., Borges, B., Donato, J., Allen, S. J., Bellefontaine, N., Wang, M., Zhao, J. J., Kozloff, K., Hill, J. W., & Elias, C. (2017) · JCI Insight · doi:10.1172/jci.insight.96728 · Cited by 33
“This is in line with the reduced body length of leptin signaling deficient mice and the lack of a growth phenotype following inactivation of STAT signaling in LR cells (23, 24).”
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 41
Ha, S., Baver, S. B., Huo, L., Gata, A., Hairston, J. E., Huntoon, N., Li, W., Zhang, T., Benecchi, E. J., Ericsson, M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077622 · Cited by 38
“Leptin-dependent phosphorylation of the STAT3 transcription factor is a highly specific CNS cellular marker for identification of LepRb-expressing neurons in vivo [19,30] and STAT3 activation by LepRb is critically important for normal energy balance regulation [31,32].”
BackgroundShp2 as a therapeutic target for leptin resistance and obesity
Feng, G. (2006) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.10.1.135 · Cited by 39
“The requirement for STAT3 in leptin signalling through LepRb in hypothalamus to control energy balance has been well documented [31-33].”
BackgroundNakata, M., Yamamoto, S., Okada, T., Gantulga, D., Okano, H., Ozawa, K., & Yada, T. (2016) · International Journal of Obesity · doi:10.1038/ijo.2015.201 · Cited by 39
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
“LepRb-mediated STAT3 signaling (LepRb→STAT3) is very important for many aspects of leptin action in vivo, as mice expressing a “knocked-in” mutant LepRb (Lepr; s/s mice) from within the endogenous Lepr locus fail to mediate leptin-stimulated STAT3 signaling and are hyperphagic, obese, and insulin resistant, in additio…”
BackgroundMethodSelf-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
Self-citationLeptin and the central control of feeding behavior
Pénicaud, L., Meillon, S., & Brondel, L. (2012) · Biochimie · doi:10.1016/j.biochi.2012.04.013 · Cited by 49
Leptin, 20years of searching for glucose homeostasis
Fernández-Formoso, G., Perez‐Sieira, S., González-Touceda, D., Diéguez, C., & Tovar, S. A. (2015) · Life Sciences · doi:10.1016/j.lfs.2015.02.008 · Cited by 39
Ma, W., Fuentes, G., Shi, X., Verma, C. S., Radda, G. K., & Han, W. (2014) · Biochemical Journal · doi:10.1042/bj20141109 · Cited by 36
Hepatitis C Virus Activates Bcl-2 and MMP-2 Expression through Multiple Cellular Signaling Pathways
Li, Y., Zhang, Q., Liu, Y., et al. (2012) · Journal of Virology · doi:10.1128/jvi.01136-12 · Cited by 37
“It has been reported that phosphorylation of STAT3 is regulated by the JNK and ERK signaling cascade (4, 9, 61).”
BackgroundHypothalamic redox balance and leptin signaling - Emerging role of selenoproteins
Gong, T., Torres, D. J., Berry, M. J., & Pitts, M. W. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.02.038 · Cited by 38
D’Occhio, M. J., Campanile, G., & Baruselli, P. S. (2020) · Biology of Reproduction · doi:10.1093/biolre/ioaa135 · Cited by 41
Leptin, Resistin, and Proprotein Convertase Subtilisin/Kexin Type 9
Macchi, C., Greco, M. F., Botta, M., Sperandeo, P., Dongiovanni, P., Valenti, L. V. C., Cicero, A. F. G., Borghi, C., Lupo, M. G., Romeo, S., et al. (2020) · American Journal Of Pathology · doi:10.1016/j.ajpath.2020.07.016 · Cited by 37
Hypothalamic Grb10 enhances leptin signalling and promotes weight loss
Liu, H., He, Y., Bai, J., Zhang, C., Zhang, F., Yang, Y., Luo, H., Yu, M., Liu, H., Tu, L., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-022-00701-x · Cited by 37
A novel form of ciliopathy underlies hyperphagia and obesity in Ankrd26 knockout mice
Acs, P. I., Bauer, P. O., Mayer, B., Bera, T. K., MacAllister, R., Mezey, É., & Pastan, I. H. (2014) · Brain Structure and Function · doi:10.1007/s00429-014-0741-9 · Cited by 38
“The phosphorylation of STAT3 (signal transducer and activator of transcription 3) following leptin activation has been well documented and accepted as a sign of intact leptin responsiveness in the ARC after leptin administration (Bates et al. 2003).”
InfluentialBo, E., Farinetti, A., Marraudino, M., Sterchele, D., Eva, C. E., Gotti, S., & Panzica, G. (2016) · Andrology · doi:10.1111/andr.12222 · Cited by 37
“These actions are, therefore, finalized to increase energy expenditure (Friedman & Halaas, 1998; Bates et al., 2003).”
BackgroundHomeostatic and pathogenic roles of the GM3 ganglioside
Inokuchi, J., Kanoh, H., Inamori, K., Nagafuku, M., Nitta, T., & Fukase, K. (2021) · FEBS Journal · doi:10.1111/febs.16076 · Cited by 38
Zoledronic 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
“The signaling deficits of s/s and l/l mice have been previously verified in the central nervous system [Bates et al., 2003; Bjornholm et al., 2007] and in peripheral macrophages [Mancuso et al.”
BackgroundMethodLeptin controls hair follicle cycling
Watabe, R., Yamaguchi, T., Kabashima‐Kubo, R., et al. (2014) · Experimental Dermatology · doi:10.1111/exd.12335 · Cited by 36
Is leptin resistance the cause or the consequence of diet-induced obesity?
de Git, K. C. G., Peterse, C., Beerens, S., Luijendijk, M. C. M., van der Plasse, G., la Fleur, S. E., & Adan, R. A. H. (2018) · International Journal of Obesity · doi:10.1038/s41366-018-0111-4 · Cited by 40
Cuvelier, E., Méquinion, M., Leghay, C., Sibran, W., Stiévenard, A., Sarchione, A., Bonte, M.-A., Vanbesien-Mailliot, C., Viltart, O., Saitoski, K., et al. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00321 · Cited by 40
“In vivo studies have provided evidence indicating that STAT3 activation in the hypothalamus is critical to the regulation of food intake and energy balance, particularly in the functioning of leptin (Bates et al., 2003; Buettner et al., 2006).”
BackgroundGuillebaud, F., Duquenne, M., Djelloul, M., Clément, P., Poirot, K., Roussel, G., Seddik, R., Lanfray, D., Morin, F., Jean, A., et al. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-01944-z · Cited by 35
“Based on our data, it is tempting to speculate that endozepines could modulate leptin sensitivity in the ARC in response to feeding by both increasing the shuttling of circulating leptin via the activation of the LepR-ERK signaling pathway in tanycytes [15, 68] and upregulating the expression of LepRb in the hypothala…”
BackgroundInfluentialHypothalamic Malonyl-Coenzyme A and the Control of Energy Balance
Wolfgang, M. J., & Lane, M. D. (2008) · Molecular Endocrinology · doi:10.1210/me.2007-0538 · Cited by 37
Leptin inhibits rosiglitazone-induced adipogenesis in murine primary adipocytes
Rhee, S. D., Sung, Y.-Y., Jung, W. H., & Cheon, H. G. (2008) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.08.018 · Cited by 34
Kaelin, C. B., Gong, L., Xu, A. W., Yao, F., Hockman, K., Morton, G. J., Schwartz, M. W., Barsh, G. S., & MacKenzie, R. G. (2006) · Molecular Endocrinology · doi:10.1210/me.2006-0107 · Cited by 35
“Many Agrp neurons also express the leptin receptor (18), leptin administration causes a rapid accumulation of pStat3 in Agrp neurons (19), mice with mutated leptin receptors that cannot bind Stat3 are obese with elevated Agrp mRNA (20), and consensus sites for pStat binding exist in the 5 flanking region of Agrp (21).”
BackgroundSelf-citationStructure and Function of Bone Marrow Adipocytes
de Paula, F. J. A., & Rosen, C. J. (2017) · Comprehensive physiology · doi:10.1002/cphy.c170010 · Cited by 39
“The effects of leptin start with the activation of JAK2 leading to STAT3 phosphorylation which, after translocation to the nucleus, will act as a transcription factor for phospho-STAT3 target genes (22,252).”
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
Self-citationPan, 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
“Interestingly, however, although the lack of leptin or LepRb throughout the body increased Agrp andNpy expression many-fold (11), the expression of these genes was not dysregulated in LepRbKO mice.”
BackgroundSelf-citationKokkorakis, M., Katsarou, A., Katsiki, N., & Mantzoros, C. S. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155689 · Cited by 35
Is 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
Metadata
- Authors
- 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., Neel, B. G., Schwartz, M. W., & Myers, M. G.
- Affiliations
- Joslin Diabetes Center (US)
- Beth Israel Deaconess Medical Center (US)
- University of Washington (US)
- Corresponding author
- Myers, Martin G.
- ORCID
- Venue
- Nature
- Published
- 2003-02
- Volume
- 421
- Issue
- 6925
- Pages
- 856-859
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2103270369
- Semantic Scholar
- 25ab9d73ec0d0c8fc3c6ec167cccbfe002d52c52
- Cited by
- 1,010
- References
- 25
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 19 · 2023: 21 · 2022: 34 · 2021: 35 · 2020: 50 · 2019: 32 · 2018: 46 · 2017: 35 · 2016: 48 · 2015: 52 · 2014: 66 · 2013: 67 · 2012: 54
- FWCI
- 20.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- STAT3 signaling, leptin, leptin receptor, energy homeostasis, obesity, fertility, neuropeptide Y, melanocortin system, hypothalamus, glucose homeostasis, db/db mice, hyperphagia, insulin resistance
- MeSH terms
- Alleles, alpha-MSH, Animals, Blood Glucose, Body Weight, Cell Line, Diabetes Mellitus, DNA-Binding Proteins, Energy Metabolism, Female, Homeostasis, Humans, Infertility, Male, Neuropeptide Y, Obesity, Phenotype, Receptors, Cell Surface, Reproduction, RNA, Messenger, Signal Transduction, Trans-Activators, Leptin, Estrous Cycle, STAT3 Transcription Factor, Mice, Receptors, Leptin
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