Cited by 531Regulation of Appetite and ObesityHypothalamic control of reproductive hormonesNeuropeptides and Animal Physiology

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The Melanocortin-4 Receptor: Physiology, Pharmacology, and Pathophysiology

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Tao, Ya-Xiong·2010·Endocrine Reviews

DOI 10.1210/er.2009-0037PMC PMC3365848

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Abstract

The melanocortin-4 receptor (MC4R) was cloned in 1993 by degenerate PCR; however, its function was unknown. Subsequent studies suggest that the MC4R might be involved in regulating energy homeostasis. This hypothesis was confirmed in 1997 by a series of seminal studies in mice. In 1998, human genetic studies demonstrated that mutations in the MC4R gene can cause monogenic obesity. We now know that mutations in the MC4R are the most common monogenic form of obesity, with more than 150 distinct mutations reported thus far. This review will summarize the studies on the MC4R, from its cloning and tissue distribution to its physiological roles in regulating energy homeostasis, cachexia, cardiovascular function, glucose and lipid homeostasis, reproduction and sexual function, drug abuse, pain perception, brain inflammation, and anxiety. I will then review the studies on the pharmacology of the receptor, including ligand binding and receptor activation, signaling pathways, as well as its regulation. Finally, the pathophysiology of the MC4R in obesity pathogenesis will be reviewed. Functional studies of the mutant MC4Rs and the therapeutic implications, including small molecules in correcting binding and signaling defect, and their potential as pharmacological chaperones in rescuing intracellularly retained mutants, will be highlighted.

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Items 401–502 of 502

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Koegler, F. H., Schaffhauser, A. O., Mynatt, R. L., York, D. A., & Bray, G. A. (1999) · Physiology & Behavior · doi:10.1016/s0031-9384(99)00104-3 · Cited by 47
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Yang, Y.-K., Dickinson, C. J., Zeng, Q., Li, J.-Y., Thompson, D. A., & Gantz, I. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.20.14100 · Cited by 46
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Heijboer, A. C., van den Hoek, A. M., Pijl, H., Voshol, P. J., Havekes, L. M., Romijn, J. A., & Corssmit, E. P. M. (2005) · Diabetologia · doi:10.1007/s00125-005-1838-8 · Cited by 43
Different Developmental Patterns of Melanocortin MC3 and MC4 Receptor mRNA: Predominance of Mc4 in Fetal Rat Nervous System
Kistler‐Heer, Lauber, & Lichtensteiger (1998) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.1998.00180.x · Cited by 43
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Schiöth, H. B., Lagerström, M. C., Watanobe, H., Jónsson, L., Vergoni, A. V., Ringholm, A., Skarphedinsson, J. O., Skúladóttir, G. V., Kloviņš, J., & Fredriksson, R. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb03164.x · Cited by 26
A Novel and Selective β-Melanocyte-Stimulating Hormone-Derived Peptide Agonist for Melanocortin 4 Receptor Potently Decreased Food Intake and Body Weight Gain in Diet-Induced Obese Rats
Hsiung, H. M., Hertel, J. L., Zhang, X.-Y., Smith, D. P., Smiley, D. L., Heiman, M. L., Yang, D. D., Husain, S., Mayer, J. P., Zhang, L., et al. (2005) · Endocrinology · doi:10.1210/en.2005-0177 · Cited by 26
Long-term alterations in body weight do not affect the expression of melanocortin receptor-3 and -4 mRNA in the ovine hypothalamus
Iqbal, J., Pompolo, S., Dumont, L. M., Wu, C., Mountjoy, K. G., Henry, B. A., & Clarke, I. J. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00250-0 · Cited by 25
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Fleck, B. A., Chen, Yang, W., Huntley, R., Markison, S., Nickolls, S. A., Foster, A. C., & Hoare, S. R. J. (2005) · Biochemistry · doi:10.1021/bi051316s · Cited by 25
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Smith, M. L., Prall, B. C., Nandar, W., & Cline, M. A. (2007) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2007.01639.x · Cited by 23
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Beckers, S., Mertens, I. L., Peeters, A. V., Gaal, L. V., & Hul, W. V. (2005) · International Journal of Obesity · doi:10.1038/sj.ijo.0803126 · Cited by 22
Further evidence for a significant participation of the melanocortin 4 receptor in the preovulatory prolactin surge in the rat
Watanobe, H., Yoneda, M., Kakizaki, Y., Kohsaka, A., Suda, T., & Schiöth, H. B. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00442-7 · Cited by 22
Chronic melanocortin 4 receptor blockage causes obesity without influencing sexual behavior in male rats
Vergoni, A. V., Bertolini, A., Guidetti, G., Karefilakis, V., Filaferro, M., Wikberg, J., & Schiöth, H. B. (2000) · Journal of Endocrinology · doi:10.1677/joe.0.1660419 · Cited by 21
Pharmacological and pharmacokinetic characterization of 2-piperazine-α-isopropyl benzylamine derivatives as melanocortin-4 receptor antagonists
Chen, C., Tucci, F. C., Jiang, W., Tran, J. A., Fleck, B. A., Hoare, S. R. J., Wen, J., Chen, T., Johns, M. S., Markison, S., et al. (2008) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2008.03.072 · Cited by 20
The Melanocortin-4 Receptor
Cone, R. D. (2000) · Humana Press eBooks · doi:10.1007/978-1-59259-031-5_14 · Cited by 20
A novel mutation Thr162Arg of the melanocortin 4 receptor gene in a Spanish children and adolescent population
Ochoa, M. C., Azcona, C., Biebermann, H., Brumm, H., Razquín, C., Wermter, A. ‐., Martínez, J. A., Hebebrand, J., Hinney, A., Moreno-Aliaga, M. J., et al. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.02788.x · Cited by 20
Hypothalamic melanocortin signaling and leptin resistance—Perspective of therapeutic application for obesity-diabetes syndrome
Masuzaki, H., Tanaka, T., Ebihara, K., Hosoda, K., & Nakao, K. (2009) · Peptides · doi:10.1016/j.peptides.2009.04.008 · Cited by 20
Functional Evaluation of THIQ, a Melanocortin 4 Receptor Agonist, in Models of Food Intake and Inflammation
Muceniece, R., Zvejniece, L., Vilšķe̅rsts, R., Liepinsh, E., Baumane, L., Kalvinsh, I., Wikberg, J. E. S., & Dambrova, M. (2007) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2007.00133.x · Cited by 20
Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness
de Rijke, C. E., Jackson, P. J., Garner, K. M., van Rozen, R. J., Douglas, N. R., Kas, M. J., Millhauser, G. L., & Adan, R. A. H. (2005) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.04.033 · Cited by 19
Effect of the melanocortin receptor stimulation or inhibition on ethanol intake in alcohol-preferring rats
Polidori, C., Geary, N., & Massi, M. (2005) · Peptides · doi:10.1016/j.peptides.2005.07.008 · Cited by 19
Corticotropin-releasing factor is a downstream mediator of the beta-melanocyte-stimulating hormone-induced anorexigenic pathway in chicks
Kamisoyama, H., Honda, K., Saneyasu, T., Sugahara, K., & Hasegawa, S. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.04.041 · Cited by 19
Key amino acid residues in the melanocortin-4 receptor for nonpeptide THIQ specific binding and signaling
Yang, Y., Cai, M., Chen, M., Qu, H., McPherson, D. T., Hruby, V. I., & Harmon, C. M. (2009) · Regulatory Peptides · doi:10.1016/j.regpep.2009.03.006 · Cited by 19
Cardiovascular, Renal, and Metabolic Responses to Chronic Central Administration of Agouti-Related Peptide
Tallam, L. S., Kuo, J. J., da Silva, A. A., & Hall, J. E. (2004) · Hypertension · doi:10.1161/01.hyp.0000148993.47498.b2 · Cited by 18
AgRP-deficiency could lead to increased lifespan
Redmann, S. M., & Argyropoulos, G. A. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.10.129 · Cited by 17
α-MSH and γ-MSH modulate early release of hypothalamic PGE2 and NO induced by IL-1β differently
Cragnolini, A. B., Caruso, C. M., Lasaga, M., & Scimonelli, T. N. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.09.034 · Cited by 16
Contribution of the transmembrane domain 6 of melanocortin-4 receptor to peptide [Pro5, dNal (2′)8]-γ-MSH selectivity
Chen, M., Cai, M., McPherson, D. T., Hruby, V. J., Harmon, C. M., & Yang, Y. (2008) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.09.023 · Cited by 14
Melanocortin-4 receptor in sheep: A potential site for therapeutic intervention in disease models
Sartin, J. L., Wagner, C. G., Marks, D. L., Daniel, J. A., McMahon, C. D., Obese, F. Y., & Partridge, C. (2005) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2005.02.027 · Cited by 14
MC4R Mutations—Weight before Screening!
Kublaoui, B. M., & Zinn, A. R. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0546 · Cited by 14
The melanocortin agonist melanotan II increases insulin sensitivity in OLETF rats
Banno, R., Arima, H., Sato, I., Hayashi, M., Goto, M., Sugimura, Y., Murase, T., & Oiso, Y. (2004) · Peptides · doi:10.1016/j.peptides.2004.05.007 · Cited by 11
Lack of Erectogenic Activity of a Novel Selective Melanocortin‐4 Receptor Agonist in a Clinical Experimental Model
Krishna, R., Wong, P., Stevens, C., Lepeleire, I. D., Dyck, K. V., Rosen, R. C., Gendrano, I. N., Peeters, M., Wagner, J. A., & Herman, G. A. (2008) · The Journal of Clinical Pharmacology · doi:10.1177/0091270008320925 · Cited by 10
ACTH1-24 Down-Regulates Expression of Ciliary Neurotrophic Factor mRNA in Cultured Rat Astrocyte
Kokubo, M., Asai, K., Yamamoto, N., Aoyama, M., Morikawa, M., Togari, H., Wada, Y., & Kato, T. (2002) · Pediatric Research · doi:10.1203/00006450-200212000-00022 · Cited by 9
Feeding signals to the hungry mind
Balthasar, N. (2009) · Experimental Physiology · doi:10.1113/expphysiol.2008.042226 · Cited by 7
Targeting melanocortin receptors for the treatment of obesity
Markison, S., & Foster, A. C. (2006) · Drug Discovery Today Therapeutic Strategies · doi:10.1016/j.ddstr.2006.10.011 · Cited by 7
Molecular Screening of MC4R Gene and Association with Fat Traits in Pig Resource Family
Gui, L. (2002) · Acta Genetica Sinica · Cited by 7
[Cloning and functional analysis of melanocortin 4 receptor mutation gene F261S].
Shao, X., Jia, W., Cai, S.-B., Fang, Q., Zhang, R., Lu, J., & Xiang, K. (2005) · PubMed · Cited by 6
[Molecular screening of MC4R gene and association with fat traits in pig resource family].
Liu, G.-L., Jiang, S., Xiong, Y., Zheng, R., & Qu, Y. (2002) · PubMed · Cited by 6
ACTH1-24 Down-Regulates Expression of Ciliary Neurotrophic Factor mRNA in Cultured Rat Astrocyte
KOKUBO, M. (2002) · Pediatric Research · doi:10.1203/01.pdr.0000036280.65404.f8 · Cited by 3

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Authors: Tao, Y.-X.
Affiliations: Auburn University (US)
Corresponding author: Tao, Ya-Xiong
ORCID: Tao, Ya-Xiong
Venue: Endocrine Reviews
Publisher: The Endocrine Society
Published: 2010-08-01
Volume: 31
Issue: 4
Pages: 506-543
ISSN: 0163-769X (ISSN-L)
1945-7189
DOI: 10.1210/er.2009-0037
PMC: PMC3365848
OpenAlex: W2120361515
Cited by: 531
References: 507
Citations by year: 2026: 25 · 2025: 32 · 2024: 34 · 2023: 34 · 2022: 31 · 2021: 41 · 2020: 41 · 2019: 33 · 2018: 29 · 2017: 32 · 2016: 21 · 2015: 29 · 2014: 39 · 2013: 47 · 2012: 30
FWCI: 16.04
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Endocrine Reviews (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (R15DK077213)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: melanocortin-4 receptor, energy homeostasis, monogenic obesity, MC4R mutations, cachexia, cardiovascular function, glucose homeostasis, lipid homeostasis, drug abuse, pain perception, neuroinflammation, anxiety, receptor pharmacology, ligand binding, receptor signaling pathways, pharmacological chaperones, obesity pathogenesis, small molecule drugs
MeSH terms: Amino Acid Sequence, Animals, Cachexia, Cardiovascular System, Cloning, Molecular, Energy Metabolism, Gene Expression Regulation, Glucose, Homeostasis, Humans, Molecular Sequence Data, Mutation, Obesity, Organ Specificity, Reproduction, Sexual Behavior, Signal Transduction, Sequence Alignment, Receptor, Melanocortin, Type 4, Lipid Metabolism

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The Melanocortin-4 Receptor: Physiology, Pharmacology, and Pathophysiology

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