Cited by 769Regulation of Appetite and ObesityHypothalamic control of reproductive hormonesAdipokines, Inflammation, and Metabolic Diseases

The DOI matches its Crossref record.

Proopiomelanocortin Neurons Are Direct Targets for Leptin in the Hypothalamus

Cheung, Clement C., Clifton, Donald K., Steiner, Robert A.·1997·Endocrinology

DOI 10.1210/endo.138.10.5570

Open this paper in CoChat — free account

Abstract

Leptin is a protein product of the obese (ob) gene, which is secreted by adipocytes and functions as a satiety factor to regulate food intake. The expression of the leptin receptor in several hypothalamic nuclei suggests that multiple neuronal subtypes are targets for leptin's action. Products of the proopiomelanocortin (POMC) gene are known to affect feeding behavior, and POMC neurons share a similar distribution with leptin receptor mRNA in the arcuate nucleus. We used double label in situ hybridization and computerized image analysis to test the hypothesis that POMC neurons coexpress the leptin receptor. Quantitative analysis confirmed that POMC neurons in the hypothalamus express leptin receptor mRNA. Based on this observation, we infer that POMC neurons and the products of the POMC gene may be part of the signaling pathway mediating leptin's action on feeding and perhaps other physiological functions.

Integrity signals

Registry

Crossref · 10.1210/endo.138.10.5570

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Sorted by citations

Items 201–300 of 749

Quantification of sleep behavior and of its impact on the cross-talk between the brain and peripheral metabolism
Hanlon, E. C., & Van Cauter, E. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1101338108 · Cited by 110
Leptin116–130 Stimulates Prolactin and Luteinizing Hormone Secretion in Fasted Adult Male Rats
González, L. C., Pinilla, L., Tena‐Sempere, M., & Aguilar, E. (1999) · Neuroendocrinology · doi:10.1159/000054479 · Cited by 109
Transcription Factor STAT3 in Leptin Target Neurons of the Rat Hypothalamus
Håkansson, M., & Meister, B. (1998) · Neuroendocrinology · doi:10.1159/000054392 · Cited by 108
Effects of In Vivo and In Vitro Administration of Ghrelin, Leptin and Neuropeptide Mediators on Pulsatile Gonadotrophin‐Releasing Hormone Secretion from Male Rat Hypothalamus Before and After Puberty
Lebrethon, M. C., Aganina, A., Fournier, M., Gérard, A., Parent, A., & Bourguignon, J.-P. (2006) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2006.01518.x · Cited by 109
Cognitive and autonomic determinants of energy homeostasis in obesity
Richard, D. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.103 · Cited by 113
Implications of leptin in neuroendocrine regulation of male reproduction
Landry, D. A., Cloutier, F., & Martin, L. J. (2013) · Reproductive Biology · doi:10.1016/j.repbio.2012.12.001 · Cited by 111
Fetal and perinatal programming of appetite
Cripps, R. L., Martin‐Gronert, M. S., & Ozanne, S. E. (2005) · Clinical Science · doi:10.1042/cs20040367 · Cited by 108
Relevance of animal models to human eating disorders and obesity
Casper, R. C., Sullivan, E. L., & Tecott, L. H. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1102-2 · Cited by 111
“A discrete central locus of leptin action on the melanocortin system was further suggested by neuroanatomical (Cheung et al. 1997) and pharmacological evidence (Kask et al.”
Background
Rho-kinase regulates energy balance by targeting hypothalamic leptin receptor signaling
Hu, H., Kong, D., Byun, K. H., Ye, C., Koda, S., Lee, D. H., Oh, B., Lee, S. W., Lee, B., Zabolotny, J. M., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3207 · Cited by 106
Neuromedin U and Neuromedin U receptor‐2 expression in the mouse and rat hypothalamus: effects of nutritional status
Graham, E. S., Turnbull, Y. D., Fotheringham, P., Nilaweera, K. N., Mercer, J. G., Morgan, P. J., & Barrett, P. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02079.x · Cited by 103
Gene variants and binge eating as predictors of comorbidity and outcome of treatment in severe obesity
Potoczna, N., Branson, R., Kral, J. G., Piec, G., Steffen, R., Ricklin, T. P., Hoehe, M. R., Lentes, K., & Horber, F. (2004) · Journal of Gastrointestinal Surgery · doi:10.1016/j.gassur.2004.09.032 · Cited by 103
Evidence for the Existence of Distinct Central Appetite, Energy Expenditure, and Ghrelin Stimulation Pathways as Revealed by Hypothalamic Site-Specific Leptin Gene Therapy
Bagnasco, M., Dube, M. G., Kalra, P. S., & Kalra, S. P. (2002) · Endocrinology · doi:10.1210/en.2002-220505 · Cited by 103
“(AgrP) and in proopiomelanocortin (POMC) neurons producing the anorexigenic peptide, -MSH (5, 6, 30, 31).”
Background
Activation of SOCS-3 Messenger Ribonucleic Acid in the Hypothalamus by Ciliary Neurotrophic Factor
Bjørbæk, C., Elmquist, J. K., El-Haschimi, K., Kelly, J., Ahima, R. S., Hileman, S. M., & Flier, J. S. (1999) · Endocrinology · doi:10.1210/endo.140.5.6736 · Cited by 107
Neuroendocrine mechanisms regulating food intake and body weight
McMinn, J. E., Baskin, D. G., & Schwartz, M. W. (2000) · Obesity Reviews · doi:10.1046/j.1467-789x.2000.00007.x · Cited by 97
“The long-form of the leptin receptor is also expressed by POMC neurones in the ARC (52), most of which also express another anorectic peptide, cocaine/amphetamine-regulated transcript (CART) (53).”
Background
Hypothalamic Gene Expression in Sheep for Cocaine- and Amphetamine-Regulated Transcript, Pro-Opiomelanocortin, Neuropeptide Y, Agouti-Related Peptide and Leptin Receptor and Responses to Negative Energy Balance
Adam, C. L., Archer, Z. A., Findlay, P. A., Thomas, E. L., & Marie, M. (2002) · Neuroendocrinology · doi:10.1159/000054716 · Cited by 99
Hypophysiotropic Thyrotropin-Releasing Hormone-Synthesizing Neurons in the Human Hypothalamus Are Innervated by Neuropeptide Y, Agouti-Related Protein, and -Melanocyte-Stimulating Hormone
Mihály, E., Fekete, C., Tatro, J. B., Liposits, Z., Stopa, E. G., & Lechan, R. M. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.7.6662 · Cited by 106
CNS Melanocortin System Involvement in the Regulation of Food Intake
Benoit, S. C., Schwartz, M. W., Baskin, D. G., Woods, S. C., & Seeley, R. J. (2000) · Hormones and Behavior · doi:10.1006/hbeh.2000.1588 · Cited by 100
Obesity: molecular bases of a multifactorial problem
Palou, A., Serra, F. A., Bonet, M. L., & Picó, C. (2000) · European Journal of Nutrition · doi:10.1007/s003940070017 · Cited by 99
“I Am I and My Bacterial Circumstances”: Linking Gut Microbiome, Neurodevelopment, and Depression
Lima‐Ojeda, J. M., Rupprecht, R., & Baghai, T. C. (2017) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2017.00153 · Cited by 104
“Also, the peptide hormone known as α-melanocyte stimulating hormone (α-MSH), an agonist of the MC4R (32), is produced by POMC neurons from the ARC (47).”
BackgroundInfluential
Ciliary neurotrophic factor improves diabetic parameters and hepatic steatosis and increases basal metabolic rate in db/db mice
Sleeman, M. W., Garcia, K., Liu, R., Murray, J. D., Malinova, L., Moncrieffe, M., Yancopoulos, G. D., & Wiegand, S. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2335926100 · Cited by 100
GABAergic Nature of Hypothalamic Leptin Target Neurones in the Ventromedial Arcuate Nucleus
Ovesjö, M., Gamstedt, M., Collin, M., & Meister, B. (2001) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2001.00662.x · Cited by 100
Distribution, function, and properties of leptin receptors in the brain
Funahashi, H., Yada, T., Suzuki, R., & Shioda, S. (2003) · International review of cytology · doi:10.1016/s0074-7696(05)24001-9 · Cited by 98
Stress, Neuropeptides, and Feeding Behavior: A Comparative Perspective
Carr, J. A. (2002) · Integrative and Comparative Biology · doi:10.1093/icb/42.3.582 · Cited by 99
“These findings, with evidence that leptin receptors are expressed within arcuate POMC neurons (Cheung et al., 1997; Håkansson et al., 1998), point to a critical role for melanocortins in regulating feeding behavior.”
Background
Central melanocortin system modulates energy intake and expenditure of obese and lean Zucker rats
Hwa, J. J., Ghibaudi, L., Gao, J., & Parker, E. M. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.281.2.r444 · Cited by 96
“Leptin activates neuropeptide Y (NPY)/agouti-related peptide (AGRP)containing neurons and proopiomelanocortin (POMC)/ cocaine- and amphetamine-regulated transcript (CART)-containing neurons of the ventromedial and ventrolateral arcuate nucleus, respectively (4, 9, 12), via activation of the long isoform of the leptin…”
Background
Hypoxia Inducible Factor as a Central Regulator of Metabolism – Implications for the Development of Obesity
Gaspar, J. M., & Velloso, L. A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00813 · Cited by 97
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.-C., Osborne-Lawrence, S. L., Rovinsky, S. A., Elmquist, J. K., & Zigman, J. M. (2011) · The Journal of Comparative Neurology · doi:10.1002/cne.22690 · Cited by 99
“With respect to leptin sensing, most NPY/AgRP neurons also express LepRb (Cheung et al., 1997).”
Background
Balancing ovulation and anovulation: integration of the reproductive and energy balance axes by neuropeptides
Evans, J. J., & Anderson, G. M. (2012) · Human Reproduction Update · doi:10.1093/humupd/dms004 · Cited by 101
Hypothalamic neuropeptide mechanisms for regulating energy balance: from rodent models to human obesity
Mercer, J. G., & Speakman, J. R. (2001) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(00)00053-1 · Cited by 94
Photoperiod Regulates Growth, Puberty and Hypothalamic Neuropeptide and Receptor Gene Expression in Female Siberian Hamsters1
Adam, C. L., Moar, K. M., Logie, T. J., et al. (2000) · Endocrinology · doi:10.1210/endo.141.12.7807 · Cited by 94
Neurobiology of overeating and obesity: The role of melanocortins and beyond
Pandit, R., de Jong, J. W., Vanderschuren, L. J. M. J., & Adan, R. A. H. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2011.01.034 · Cited by 95
“Both populations express the leptin receptor, project to other hypothalamic nuclei and have an opposing action on energy balance (Schwartz et al., 1996; Cheung et al., 1997).”
Background
Differential role of melanocortins in mediating leptin's central effects on feeding and reproduction
Hohmann, J. G., Teal, T. H., Clifton, D. K., Davis, J., Hruby, V. J., Han, G., & Steiner, R. A. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.278.1.r50 · Cited by 91
“In the rat and monkey, most neurons in the arcuate nucleus that express POMC also express leptin receptor (9, 16), and leptin treatment in ob/ob mice induces POMC gene expression (39, 46, 54).”
BackgroundSelf-citation
Melanocortin receptor signaling through mitogen-activated protein kinase in vitro and in rat hypothalamus
Daniels, D., Patten, C. S., Roth, J. D., Yee, D. K., & Fluharty, S. J. (2003) · Brain Research · doi:10.1016/s0006-8993(03)03162-7 · Cited by 92
Regulation of Hypothalamic Proopiomelanocortin by Leptin in Lean and Obese Rats
Körner, J., Chua, S. C., Williams, J. A., Leibel, R. L., & Wardlaw, S. L. (1999) · Neuroendocrinology · doi:10.1159/000054499 · Cited by 89
Central administration of α-melanocyte stimulating hormone inhibits fasting- and neuropeptide Y-induced feeding in neonatal chicks
Kawakami, S.-I., Bungo, T., Ando, R., Ohgushi, A., Shimojo, M., Masuda, Y., & Furuse, M. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00344-7 · Cited by 90
Saturated fatty acids and insulin resistance
Funaki, M. (2009) · The Journal of Medical Investigation · doi:10.2152/jmi.56.88 · Cited by 90
“Leptin also increases lipid oxidation in the liver and lipolysis in skeletal muscle and adipocytes to control wholebody energy balance (9, 10).”
Background
Actions of CCK in the controls of food intake and body weight: Lessons from the CCK-A receptor deficient OLETF rat
Bi, S., & Moran, T. H. (2002) · Neuropeptides · doi:10.1054/npep.2002.0895 · Cited by 88
Cloning and Distribution of Galanin-Like Peptide mRNA in the Hypothalamus and Pituitary of the Macaque
Cunningham, M. J., Scarlett, J. M., & Steiner, R. A. (2002) · Endocrinology · doi:10.1210/endo.143.3.8661 · Cited by 96
Self-citation
Leptin reduces Atlantic salmon growth through the central pro-opiomelanocortin pathway
Murashita, K., Jordal, A. O., Nilsen, T. O., Stefansson, S. O., Kurokawa, T., Björnsson, B. T., Moen, A. G., & Rønnestad, I. (2010) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2010.09.001 · Cited by 90
“POMC neurons in the hypothalamus contain the long form of leptin receptor (Cheung et al., 1997), and leptin raises mRNA levels of POMC (Schwartz et al.”
Background
The melanocortin receptors and their accessory proteins
Ramachandrappa, S., Gorrigan, R. J., Clark, A. J. L., & Chan, L. F. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00009 · Cited by 87
“MC4R is widely expressed in the central nervous system where it is abundant in several regions including the paraventricular nucleus (PVN) of the hypothalamus (Mountjoy et al., 1994).”
BackgroundInfluential
Neuroendocrine control of appetite and metabolism
Yoo, E.-S., Yu, J., & Sohn, J. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00597-9 · Cited by 92
Targeted deletion of melanocortin receptor subtypes 3 and 4, but not CART, alters nutrient partitioning and compromises behavioral and metabolic responses to leptin
Zhang, Y., Kilroy, G. E., Henagan, T. M., Prpic‐Uhing, V., Richards, W. G., Bannon, A. W., Mynatt, R. L., & Gettys, T. W. (2005) · The FASEB Journal · doi:10.1096/fj.05-3851com · Cited by 87
Peripheral tissue–brain interactions in the regulation of food intake
López, M., Tovar, S. A., Vazquez, M. J., Williams, L. M., & Diéguez, C. (2007) · Proceedings of The Nutrition Society · doi:10.1017/s0029665107005368 · Cited by 87
“GHS-R mRNA is expressed in neurons in the ARC co-expressing NPY and agouti-related peptide (AgRP; Guan et al. 1997; Tannenbaum et al. 1998; Willesen et al. 1999; Zigman et al. 2006), and the central administration of ghrelin increases the mRNA content of NPY and AgRP in the ARC in fed and fasting conditions (Kamegai e…”
BackgroundInfluential
Central Pro-opiomelanocortin Gene Delivery Results in Hypophagia, Reduced Visceral Adiposity, and Improved Insulin Sensitivity in Genetically Obese Zucker Rats
Li, G., Mobbs, C. V., & Scarpace, P. J. (2003) · Diabetes · doi:10.2337/diabetes.52.8.1951 · Cited by 88
Deletion of the Nhlh2 Transcription Factor Decreases the Levels of the Anorexigenic Peptides α Melanocyte-Stimulating Hormone and Thyrotropin-Releasing Hormone and Implicates Prohormone Convertases I and II in Obesity
Jing, E., Nillni, E. A., Sanchez, V. C., Stuart, R. C., & Good, D. J. (2004) · Endocrinology · doi:10.1210/en.2003-0834 · Cited by 85
The effects of Beta-Endorphin: state change modification
Veening, J. G., & Barendregt, H. P. (2015) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-12-3 · Cited by 89
“Most of the POMC-neurons express leptin receptors [86,87], while processing of the POMC-derived peptides is regulated by energy balance [87-90].”
Background
The leptin-dependent and -independent melanocortin signaling system: regulation of feeding and energy expenditure
Shimizu, H., Inoue, K., & Mori, M. (2007) · Journal of Endocrinology · doi:10.1677/joe-06-0144 · Cited by 88
“All POMC neurons do not express leptin receptors in the hypothalamus (Cheung et al. 1997, Munzberg et al. 2003), suggesting the existence of a leptin-unrelated melanocortin signaling system.”
BackgroundInfluential
Distribution of galanin messenger RNA-expressing cells in murine brain and their regulation by leptin in regions of the hypothalamus
Cheung, C. C., Hohmann, J. G., Clifton, D. K., & Steiner, R. A. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00012-4 · Cited by 85
“The following areas were included in the analysis: Arc, DMN and PeN.”
BackgroundMethodInfluentialSelf-citation
Pro‐Opiomelanocortin ( POMC ) Neurones, POMC ‐Derived Peptides, Melanocortin Receptors and Obesity: How Understanding of this System has Changed Over the Last Decade
Mountjoy, K. G. (2015) · Journal of Neuroendocrinology · doi:10.1111/jne.12285 · Cited by 91
Biased signaling at neural melanocortin receptors in regulation of energy homeostasis
Yang, L.-K., & Tao, Y. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.04.010 · Cited by 84
“Among these external stimuli, leptin is the most significant ligand, circulating at levels proportional to the body fat mass to act on the full-length leptin receptor (LepRb) highly expressed in first order neurons [58, 64], thus stimulating the POMC neurons to increase α-MSH production and suppressing AgRP neurons to…”
Background
Hypothalamic melanocortin neurons integrate signals of energy state
Cowley, M. A. (2003) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2003.08.087 · Cited by 86
TRAP-seq defines markers for novel populations of hypothalamic and brainstem LepRb neurons
Allison, M. B., Patterson, C. M., Krashes, M. J., Lowell, B. B., Myers, M. G., & Olson, D. P. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.01.012 · Cited by 81
Sexually different actions of leptin in proopiomelanocortin neurons to regulate glucose homeostasis
Shi, H., Strader, A. D., Sorrell, J. E., Chambers, J. B., Woods, S. C., & Seeley, R. J. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00704.2007 · Cited by 85
Enhanced Leptin Sensitivity, Reduced Adiposity, and Improved Glucose Homeostasis in Mice Lacking Exchange Protein Directly Activated by Cyclic AMP Isoform 1
Yan, J., Mei, F. C., Cheng, H., Lao, D. H., Hu, Y., Wei, J., Patrikeev, I., Hao, D., Stutz, S. J., Dineley, K. T., et al. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.01227-12 · Cited by 88
Developmental Programming of Energy Balance and Its Hypothalamic Regulation
Remmers, F., & de Waal, H. A. D. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0028 · Cited by 85
“Both of these populations coexpress receptors for peripheral signals, including those for leptin (40, 78, 79), insulin (80, 81), and ghrelin (82, 83).”
Background
A potential role for hypothalamomedullary POMC projections in leptin-induced suppression of food intake
Zheng, H., Patterson, L. M., Rhodes, C. J., Louis, G. W., Skibicka, K. P., Grill, H. J., Myers, M. G., & Berthoud, H. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00619.2009 · Cited by 84
Growth Hormone Overexpression in the Central Nervous System Results in Hyperphagia-Induced Obesity Associated With Insulin Resistance and Dyslipidemia
Bohlooly‐Y, M., Olsson, B., Bruder, C. E. G., Lindén, D., Sjögren, K., Bjursell, M., Egecioglu, E., Svensson, L., Brodin, P., Waterton, J. C., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.1.51 · Cited by 83
“Intracerebroventricular (ICV) injection of leptin decreases food intake and body weight (28) and may be acting through the proopiomelanocortin (POMC) and leptin receptor expressing-neurones in the hypothalamic arcuate nucleus (29).”
Background
Leptin in human reproduction
Messinis, I. E. (1999) · Human Reproduction Update · doi:10.1093/humupd/5.1.52 · Cited by 81
“This suggested that leptin is not the signal that triggers the onset of puberty, but rather it plays a permissive role, acting as a metabolic gate for puberty to progress (Cheung et al., 1997b).”
Background
Comparing the hypothalamic and extrahypothalamic actions of endogenous hyperleptinemia
Wang, Z.-W., Zhou, Y.-T., Kakuma, T., Lee, Y., Higa, M., Kalra, S. P., Dube, M. G., Kalra, P. S., & Unger, R. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.18.10373 · Cited by 81
Identifying the efferent projections of leptin‐responsive neurons in the dorsomedial hypothalamus using a novel conditional tracing approach
Gautron, L., Lazarus, M., Scott, M. M., Saper, C. B., & Elmquist, J. K. (2010) · The Journal of Comparative Neurology · doi:10.1002/cne.22323 · Cited by 81
“Accordingly, our group and many others have found that leptin receptors are expressed in multiple brain sites, any number of which could mediate the varied actions of leptin (Mercer et al., 1996; Cheung et al., 1997; Fei et al., 1997; Elmquist et al., 1998b).”
Background
Hypothalamic AMPK as a Mediator of Hormonal Regulation of Energy Balance
Wang, B., & Cheng, K. K. Y. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113552 · Cited by 87
Various Dietary Fats Differentially Change the Gene Expression of Neuropeptides Involved in Body Weight Regulation in Rats
Dziedzic, B., Szemraj, J., Bartkowiak, J., & Walczewska, A. (2007) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2007.01541.x · Cited by 81
Evidence for involvement of the melanocortin MC4 receptor in the effects of leptin on food intake and body weight
Kask, A., Rägo, L., Wikberg, J. E. S., & Schiöth, H. B. (1998) · European Journal of Pharmacology · doi:10.1016/s0014-2999(98)00699-2 · Cited by 82
Duodenal Lipid Sensing Activates Vagal Afferents to Regulate Non-Shivering Brown Fat Thermogenesis in Rats
Blouet, C., & Schwartz, G. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051898 · Cited by 81
“Prior studies demonstrated that intestinal infusions of MK329 were sufficient to block the ability of duodenal CCK to inhibit hepatic glucose production [36], but these studies did not preclude the possibility that the MK329 acted outside the lumen, at other peripheral or central CCKA receptor sites.”
Background
Molecular biology and physiology of the melanocortin system in fish: A review
Metz, J. R., Peters, J. J. M., & Flik, G. (2006) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2006.03.001 · Cited by 84
STZ-induced diabetes decreases and insulin normalizes POMC mRNA in arcuate nucleus and pituitary in rats
Kim, E., Grace, M. K., Welch, C. C., Billington, C. J., & Levine, A. S. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.5.r1320 · Cited by 81
“ventricular injection of leptin increases mRNA levels of POMC in the Arc of ob/ob mice (30, 33), and the leptin receptor is colocalized with POMC-containing neurons in the Arc (5, 15).”
Background
Effect of Fasting and Leptin Deficiency on Hypothalamic Neuropeptide Y Gene Transcription in Vivo Revealed by Expression of a lacZ Reporter Gene
Schwartz, M. W., Erickson, J. C., Baskin, D. G., & Palmiter, R. D. (1998) · Endocrinology · doi:10.1210/endo.139.5.6000 · Cited by 83
Changes in Hypothalamic Agouti-Related Protein (AGRP), but not α-MSH or Pro-Opiomelanocortin Concentrations in Dietary-Obese and Food-Restricted Rats
Harrold, J. A., Williams, G., & Widdowson, P. S. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0675 · Cited by 80
Role of Signal Transducer and Activator of Transcription 3 in Regulation of Hypothalamic trh Gene Expression by Leptin
Huo, L., Münzberg, H., Nillni, E. A., & Bjørbæk, C. (2004) · Endocrinology · doi:10.1210/en.2003-1242 · Cited by 78
The neuroanatomical function of leptin in the hypothalamus
van Swieten, M. M. H., Pandit, R., Adan, R. A. H., & Plasse, G. (2014) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2014.05.004 · Cited by 87
Divergent Leptin Signaling in Proglucagon Neurons of the Nucleus of the Solitary Tract in Mice and Rats
Huo, L., Gamber, K. M., Grill, H. J., & Bjørbæk, C. (2007) · Endocrinology · doi:10.1210/en.2007-0633 · Cited by 80
The pro-opiomelanocortin genes in rainbow trout (Oncorhynchus mykiss): duplications, splice variants, and differential expression
Leder, E. H., & Silverstein, J. T. (2006) · Journal of Endocrinology · doi:10.1677/joe.1.06283 · Cited by 79
“In mammals, POMC neurons in the hypothalamus contain the leptin receptor (Cheung et al. 1997).”
Authentic Cell-Specific and Developmentally Regulated Expression of Pro-Opiomelanocortin Genomic Fragments in Hypothalamic and Hindbrain Neurons of Transgenic Mice
Young, J. I., Otero, V., Cerdán, M. G., Falzone, T. L., Chan, E., Low, M. J., & Rubinstein, M. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-17-06631.1998 · Cited by 80
“Leptin receptors are expressed in POMC hypothalamic neurons (Cheung et al., 1997), and leptin-induced fasting is prevented by melanocortin receptor antagonists (Seeley et al., 1997).”
Neuroanatomical Framework of the Metabolic Control of Reproduction
Hill, J. W., & Elias, C. F. (2018) · Physiological Reviews · doi:10.1152/physrev.00033.2017 · Cited by 80
“However, control pair-fed mice showed delayed sexual maturation, suggesting that higher leptin levels in leptin-treated animals neutralized the delay in puberty caused by a state of negative energy balance (76, 77, 187).”
Background
Implications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction
Antonio Zorzano, A., & Claret, M. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00101 · Cited by 83
“Leptin and ghrelin are prototypical examples of metabolic signals of energy surfeit and deficit respectively, and POMC and AgRP neurons are direct targets of both hormones (Cheung et al., 1997; Elias et al., 1999; Willesen et al., 1999; Cowley et al., 2001).”
Background
Does body mass play a role in the regulation of food intake?
Speakman, J. R., Stubbs, R. J., & Mercer, J. G. (2002) · Proceedings of The Nutrition Society · doi:10.1079/pns2002194 · Cited by 79
Regulation of thermogenesis by the central melanocortin system
Fan, W., Voss-Andreae, A., Cao, W.-H., & Morrison, S. F. (2005) · Peptides · doi:10.1016/j.peptides.2004.11.033 · Cited by 77
Cell and Molecular Cell Biology of Melanin-Concentrating Hormone
Griffond, B., & Baker, B. I. (2002) · International review of cytology · doi:10.1016/s0074-7696(02)13016-6 · Cited by 78
Overeating of palatable food is associated with blunted leptin and ghrelin responses
Lindqvist, A., de la Cour, C. D., Stegmark, A., Håkanson, R., & Erlanson‐Albertsson, C. (2005) · Regulatory Peptides · doi:10.1016/j.regpep.2005.05.002 · Cited by 83
“Serum leptin increases after feeding and is thought to induce satiety by interfering with the release of neuropeptides, such as NPY [27,28] and proopiomelanocortin-derived peptides [29,30], from neurons in the hypothalamus.”
Background
Application of probiotics for sustainable and environment-friendly aquaculture management - A review
Amenyogbe, E. (2023) · Cogent Food & Agriculture · doi:10.1080/23311932.2023.2226425 · Cited by 84
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
“Peripheral CB1R blockade restores hypothalamic leptin sensitivity via POMC signaling Since leptin activates the anorexigenic POMC/CART neurons in the ARC [14,16], we next explored whether peripheral CB1R blockade affects this neuronal pathway.”
Background
Corticotropin-Releasing Hormone-Mediated Pathway of Leptin to Regulate Feeding, Adiposity, and Uncoupling Protein Expression in Mice
Masaki, T., Yoshimichi, G., Chiba, S., Yasuda, T., Noguchi, H., Kakuma, T., Sakata, T., & Yoshimatsu, H. (2003) · Endocrinology · doi:10.1210/en.2003-0301 · Cited by 77
“These peptides include neuropeptide Y (12), agouti-related protein (13), proopiomelanocortinderived peptide (14, 15), and CRH (16–19).”
Hypothalamic proopiomelanocortin (POMC) neurons have a cholinergic phenotype
Meister, B., Gömüç, B., Suarez, E., Ishii, Y., Dürr, K., & Gillberg, L. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05157.x · Cited by 75
“…Neuroscience Societies and Blackwell Publishing Ltd European Journal of Neuroscience, 24, 2731–2740 POMC neurons in the hypothalamic arcuate nucleus are activated by leptin and mediate part of leptin’s central actions to influence energy balance (Cheung et al., 1997; see Elmquist et al., 2005).”
Background
Review of the role of the nervous system in glucose homoeostasis and future perspectives towards the management of diabetes
Güemes, A., & Georgiou, P. (2018) · Bioelectronic Medicine · doi:10.1186/s42234-018-0009-4 · Cited by 79
Leptin Induces Phosphorylation of Neuronal Nitric Oxide Synthase in Defined Hypothalamic Neurons
Donato, J., Frazão, R., Fukuda, M., Vianna, C. R., & Elias, C. F. (2010) · Endocrinology · doi:10.1210/en.2010-0651 · Cited by 76
Downregulation of Fasting-Induced cAMP Response Element-Mediated Gene Induction by Leptin in Neuropeptide Y Neurons of the Arcuate Nucleus
Shimizu‐Albergine, M., Ippolito, D. L., & Beavo, J. A. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-04-01238.2001 · Cited by 76
“(Cheung et al., 1997; Håkansson et al., 1998), and POMC and NPY neurons are synaptically linked in the Arc (Horvath et al.”
Background
Attenuation of Diabetic Hyperphagia in Neuropeptide Y–Deficient Mice
Sindelar, D. K., Mystkowski, P., Marsh, D. J., Palmiter, R. D., & Schwartz, M. W. (2002) · Diabetes · doi:10.2337/diabetes.51.3.778 · Cited by 76
“These effects are likely mediated, at least in part, via direct stimulatory effects of leptin, since a majority of these neurons express the signaling form of the leptin receptor (OB-Rb) (27,28).”
Forebrain melanocortin signaling enhances the hindbrain satiety response to CCK-8
Blevins, J. E., Morton, G. J., Williams, D. L., Caldwell, D. W., Bastian, L. S., Wisse, B. E., Schwartz, M. W., & Baskin, D. G. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90544.2008 · Cited by 73
The role of intracerebroventricular administration of leptin in the stimulation of prothyrotropin releasing hormone neurons in the hypothalamic paraventricular nucleus
Perello, M., Stuart, R. C., & Nillni, E. A. (2006) · Endocrinology · doi:10.1210/en.2005-1533 · Cited by 74
Apelin and the proopiomelanocortin system: a new regulatory pathway of hypothalamic α-MSH release
Goazigo, A. R.-L., Bodineau, L., Mota, N. D., Jeandel, L., Chartrel, N., Knauf, C., Raad, C., Valet, P., & Llorens‐Cortés, C. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00090.2011 · Cited by 78
Oleamide and anandamide effects on food intake and sexual behavior of rats
Martı́nez-González, D., Bonilla‐Jaime, H., Morales-Otal, A., et al. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.03.080 · Cited by 74
Possible Integrative Actions of Leptin and Insulin Signaling in the Hypothalamus Targeting Energy Homeostasis
Thon, M., Hosoi, T., & Ozawa, K. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00138 · Cited by 75
The Orexigenic Activity of the Hypothalamic Neuropeptide 26RFa Is Mediated by the Neuropeptide Y and Proopiomelanocortin Neurons of the Arcuate Nucleus
Lectez, B. L. P., Jeandel, L., El-Yamani, F.-Z., et al. (2009) · Endocrinology · doi:10.1210/en.2008-1432 · Cited by 73
“Indeed, the leptin receptor has been detected on NPY (28) and POMC (29) neurons of the Arc, and the hormone is able to cross the blood-brain barrier (30).”
Background
Hypothalamic AMPK as a Regulator of Energy Homeostasis
Huynh, M. K. Q., Kinyua, A. W., Yang, D. J., & Kim, K. W. (2016) · Neural Plasticity · doi:10.1155/2016/2754078 · Cited by 78
“[4] C.”
Background
Voluntary exercise prevents the obese and diabetic metabolic syndrome of the melanocortin‐4 receptor knockout mouse
Haskell‐Luevano, C., Schaub, J. W., Andreasen, A., Haskell, K. R., Moore, M. C., Koerper, L. M., Rouzaud, F., Baker, H. V., Millard, W. J., Walter, G., et al. (2009) · The FASEB Journal · doi:10.1096/fj.08-109686 · Cited by 72
“Melanocortin agonist POMC-expressing neurons have been identified as coexpressing cocaine- and amphetamine-regulated transcript (CART) (41), the MC3R (42, 43), leptin receptors (44, 45), and the neuropeptide Y (NPY) Y1 receptor (46).”
Background
Leptin Regulates Growth Hormone-Releasing Factor, Somatostatin, and α-Melanocyte-Stimulating Hormone But Not Neuropeptide Y Release in Rat HypothalamusIn Vivo: Relation with Growth Hormone Secretion
Watanobe, H., & Habu, S. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-14-06265.2002 · Cited by 88
“The leptin-stimulated ␣-MSH release seems to be consistent with the reports that the ARC POMC neurons abundantly express leptin receptors (Cheung et al., 1997; Finn et al., 1998) and also that leptin upregulates POMC mRNA levels in the ARC (Schwartz et al., 1997; Thornton et al., 1997; Mizuno et…”
Result
Hypothalamic ER stress: A bridge between leptin resistance and obesity
Ramírez, S., & Claret, M. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.04.025 · Cited by 75
“ARC POMC and AgRP neurons express LepRb, and thus they are direct targets of leptin action [7,24,25].”
Background
Candidate gene polymorphisms in eating disorders
Hinney, A., Remschmidt, H., & Hebebrand, J. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00812-8 · Cited by 70
Kisspeptin and fertility
Hameed, S., Jayasena, C. N., & Dhillo, W. S. (2010) · Journal of Endocrinology · doi:10.1677/joe-10-0265 · Cited by 77
“One subpopulation expresses the orexigenic peptide neuropeptide Y (NPY), while another expresses the anorectic peptide a-melanocyte-stimulating hormone (a-MSH), which is derived from pro-opiomelanocortin (POMC; Cheung et al. 1997, Broberger et al. 1998).”
Background
N-acetylation of hypothalamic α-melanocyte-stimulating hormone and regulation by leptin
Guo, L., Münzberg, H., Stuart, R. C., Nillni, E. A., & Bjørbæk, C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403165101 · Cited by 71
An overview of obesity mechanisms in humans: Endocrine regulation of food intake, eating behaviour and common determinants of body weight
Theilade, S., Christensen, M., Vilsbøll, T., & Knop, F. K. (2021) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14270 · Cited by 74

Authors: Cheung, C. C., Clifton, D. K., & Steiner, R. A.
Affiliations: University of Washington (US)
Corresponding author: Steiner, Robert A.
ORCID: Steiner, Robert A.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 1997-10
Volume: 138
Issue: 10
Pages: 4489-4492
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/endo.138.10.5570
OpenAlex: W2129221666
Cited by: 769
References: 0
Citations by year: 2026: 2 · 2025: 9 · 2024: 5 · 2023: 9 · 2022: 7 · 2021: 14 · 2020: 12 · 2019: 14 · 2018: 14 · 2017: 18 · 2016: 15 · 2015: 24 · 2014: 20 · 2013: 30 · 2012: 34
FWCI: 15.45
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5t32gm007108-40)
National Institute of General Medical Sciences (5 T32-GM07108)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD 27142, R01HD027142)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: leptin, proopiomelanocortin, POMC neurons, leptin receptor, hypothalamus, arcuate nucleus, feeding behavior, satiety, food intake regulation, obese gene
MeSH terms: Animals, Carrier Proteins, Eating, Female, Gene Expression Regulation, Hypothalamus, Image Processing, Computer-Assisted, Neurons, Pro-Opiomelanocortin, Proteins, Receptors, Cell Surface, RNA, Messenger, Signal Transduction, Rats, Sprague-Dawley, In Situ Hybridization, Leptin, Rats, Receptors, Leptin

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

Proopiomelanocortin Neurons Are Direct Targets for Leptin in the Hypothalamus

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cited by

Related

Metadata

Record

About these checks