Anatomy of an Endogenous Antagonist: Relationship between Agouti-Related Protein and Proopiomelanocortin in Brain
Open accessAbstract
Agouti-related protein (AGRP) is a recently discovered orexigenic neuropeptide that inhibits the binding and action of alpha-melanocyte-stimulating hormone derived from proopiomelanocortin (POMC) at the melanocortin 3 receptor (MC3R) and melanocortin 4 receptor (MC4R) and has been proposed to function primarily as an endogenous melanocortin antagonist. To better understand the interplay between the AGRP and melanocortin signaling systems, we compared their nerve fiber distributions with each other by immunohistochemistry and their perikarya distribution with MC3R and MC4R by double in situ hybridization. Although deriving from distinct cell groups, AGRP and melanocortin terminals project to identical brain areas. Both AGRP and melanocortin neurons selectively express the MC3R, which provides a neuroanatomical basis for a dual-input circuit with biological amplification and feedback inhibition. These studies highlight a broader complexity in POMC-mediated behavior in the brain.
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AgRP neurons are found exclusively in the arcuate nucleus.
“Neurons expressing agouti-related protein (AgRP) are found exclusively in the ARC [20]”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [20]
Available anatomical evidence suggests that AgRP neurons may functionally interact with the mesolimbic pathway.
“However, available anatomical evidence suggests that AgRP neurons may functionally interact with the mesolimbic pathway [20, 62, 86], which has been implicated in depression [56].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [20]
AgRP neurons project to multiple brain regions involved in stress reactivity and reward processing.
“As AgRP neurons project to multiple brain regions involved in stress reactivity and reward processing [20, 62, 86], it is not clear which downstream targets may be contributing to the effects of AgRP neurons on depression-related behaviors.”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [20]
Another candidate downstream target of AgRP neurons is the bed nucleus of the stria terminalis (BNST).
“Another candidate downstream target of AgRP neurons is the bed nucleus of the stria terminalis (BNST) [20, 62], which has emerged as a key player in stress-related disorders [90, 91].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [20]
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Cites
The rat brain in stereotaxic coordinates
Palkovits, M. (1983) · Neuropeptides · doi:10.1016/0143-4179(83)90049-5 · Cited by 28,959 · see citing works
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein
Ollmann, M. M., Wilson, B. D., Yang, Y.-K., Kerns, J. A., Chen, Y., Gantz, I., & Barsh, G. S. (1997) · Science · doi:10.1126/science.278.5335.135 · Cited by 1,881 · see citing works
Self-citationCoexpression of Agrp and NPY in fasting-activated hypothalamic neurons
Hahn, T. M., Breininger, J. F., Baskin, D. G., & Schwartz, M. W. (1998) · Nature Neuroscience · doi:10.1038/1082 · Cited by 1,164 · see citing works
Mountjoy, K. G., Mortrud, M. T., Low, M. J., Simerly, R. B., & Cone, R. D. (1994) · Molecular Endocrinology · doi:10.1210/mend.8.10.7854347 · Cited by 1,157 · see citing works
Leptin Activates Hypothalamic CART Neurons Projecting to the Spinal Cord
Elias, C. F., Lee, C., Kelly, J., Aschkenasi, C. J., Ahima, R. S., Couceyro, P. R., Kuhar, M. J., Saper, C. B., & Elmquist, J. K. (1998) · Neuron · doi:10.1016/s0896-6273(00)80656-x · Cited by 809 · see citing works
Broberger, C., Johansen, J., Johansson, C., Schalling, M., & Hökfelt, T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.15043 · Cited by 798 · see citing works
Roselli-Rehfuss, L., Mountjoy, K. G., Robbins, L. S., Mortrud, M. T., Low, M. J., Tatro, J. B., Entwistle, M. L., Simerly, R. B., & Cone, R. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.19.8856 · Cited by 722 · see citing works
Shutter, J. R., Graham, M., Kinsey, A. C., Scully, S. A., Lüthy, R., & Stark, K. L. (1997) · Genes & Development · doi:10.1101/gad.11.5.593 · Cited by 672 · see citing works
Rossi, M., Kim, M. S., Morgan, D. G. A., Small, C. J., Edwards, C. M. B., Sunter, D., Abusnana, S., Goldstone, A. P., Russell, S. H., Stanley, S. A., et al. (1998) · Endocrinology · doi:10.1210/endo.139.10.6332 · Cited by 576 · cited 3× · see citing works
“Artificial increases in AGRP achieved pharmacologically or in transgenic animals cause elevated food intake and obesity (Graham et al., 1997; Ollmann et al., 1997; Grill et al., 1998; Rossi et al., 1998).”
BackgroundMizuno, T. M., Kleopoulos, S. P., Bergen, H., Roberts, J. L., Priest, C. A., & Mobbs, C. V. (1998) · Diabetes · doi:10.2337/diab.47.2.294 · Cited by 521 · see citing works
Mechanism of the development of obesity in animals with hypothalamic lesions.
Brobeck, J. R. (1946) · Physiological Reviews · doi:10.1152/physrev.1946.26.4.541 · Cited by 488 · cited 1× · see citing works
“Interestingly, AGRP and POMC-immunoreactive fibers are not found in the ventromedial hypothalamic nucleus, even though this region contains abundant MC3R mRNA and a-MSH binding sites and has been referred to historically as a “satiety center” (Brobeck, 1946).”
BackgroundRegulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice
Thornton, J. E., Cheung, C. C., Clifton, D. K., & Steiner, R. A. (1997) · Endocrinology · doi:10.1210/endo.138.11.5651 · Cited by 437 · cited 1× · see citing works
“Starvation and leptin deficiency cause a predominant rise in levels of AGRP mRNA rather than a decrease in POMC mRNA levels in the hypothalamus (Thornton et al., 1997; Mizuno et al., 1998; Mizuno Mobbs, 1999; Wilson et al., 1999).”
BackgroundEvidence for two separate opiate peptide neuronal systems
Watson, S., Akil, H., Richard, C. W., & Barchas, J. (1978) · Nature · doi:10.1038/275226a0 · Cited by 410 · see citing works
Self-citationMizuno, T. M., & Mobbs, C. V. (1999) · Endocrinology · doi:10.1210/endo.140.2.6491 · Cited by 387 · see citing works
Adrenocorticotropin in Rat Brain: Immunocytochemical Localization in Cells and Axons
Watson, S. J., Richard, C. W., & Barchas, J. D. (1978) · Science · doi:10.1126/science.206967 · Cited by 336 · see citing works
Self-citationGrill, H. J., Ginsberg, A. B., Seeley, R. J., & Kaplan, J. M. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-23-10128.1998 · Cited by 277 · see citing works
Haskell‐Luevano, C., Chen, P., Li, C., Chang, K., Smith, M. S., Cameron, J. L., & Cone, R. D. (1999) · Endocrinology · doi:10.1210/endo.140.3.6544 · Cited by 232 · see citing works
Interaction of Agouti protein with the melanocortin 1 receptor in vitro and in vivo
Ollmann, M. M., Lamoreux, M. L., Wilson, B. D., & Barsh, G. S. (1998) · Genes & Development · doi:10.1101/gad.12.3.316 · Cited by 226 · see citing works
Self-citationPhysiological and Anatomical Circuitry between Agouti-Related Protein and Leptin Signaling
Wilson, B. D., Bagnol, D., Kaelin, C. B., Ollmann, M. M., Gantz, I., Watson, S. J., & Barsh, G. S. (1999) · Endocrinology · doi:10.1210/endo.140.5.6728 · Cited by 203 · see citing works
Self-citationHandbook of chemical neuroanatomy — GABA and neuropeptides in the CNS
Buijs, R. M., & Swaab, D. F. (1987) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(87)90285-1 · Cited by 181 · see citing works
Bronstein, D. M., Schäfer, M. K.-H., Watson, S. J., & Akil, H. (1992) · Brain Research · doi:10.1016/0006-8993(92)91007-2 · Cited by 154 · see citing works
Self-citationCurran, E. J., & Watson, S. J. (1995) · The Journal of Comparative Neurology · doi:10.1002/cne.903610106 · Cited by 148 · see citing works
Self-citationMizuno, T. M., Kleopoulos, S. P., Bergen, H., Roberts, J. L., Priest, C. A., & Mobbs, C. V. (1998) · Diabetes · doi:10.2337/diabetes.47.2.294 · Cited by 142 · see citing works
Brain Melanocortin Receptors: From Cloning to Function
Adan, R. A. H., & Gispen, W. H. (1997) · Peptides · doi:10.1016/s0196-9781(97)00078-8 · Cited by 137 · see citing works
Mizuno, T. M. (1999) · Endocrinology · doi:10.1210/en.140.2.814 · Cited by 128 · see citing works
́ry, A. C., ̈rcs, T. G., & Palkovits, M. (1990) · Brain Research · doi:10.1016/0006-8993(90)91253-d · Cited by 120 · see citing works
Tatro, J. B. (1990) · Brain Research · doi:10.1016/0006-8993(90)90016-5 · Cited by 117 · see citing works
Massot, O., Rousselle, J. C., Fillion, M. P., Grimaldi, B., Cloëz-Tayarani, I., Fugelli, A., Prudhomme, N., Seguin, L., Rousseau, B., Plantefol, M., et al. (1996) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09375-7 · Cited by 88 · see citing works
Kruger, L., Saporta, S., & Swanson, L. W. (1995) · Cited by 59 · see citing works
Flagged first, then by citations
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Sorted by citations
Millan, M. J. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00009-6 · Cited by 3,035 · see citing works
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
Cowley, M. A., Smart, J. L., Rubinstein, M., Cerdán, M. G., Diano, S., Horvath, T. L., Cone, R. D., & Low, M. J. (2001) · Nature · doi:10.1038/35078085 · Cited by 2,356 · see citing works
Leptin Action on GABAergic Neurons Prevents Obesity and Reduces Inhibitory Tone to POMC Neurons
Vong, L., Ye, C., Yang, Z., Choi, B. J., Chua, S. C., & Lowell, B. B. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.028 · Cited by 1,238 · see citing works
“Second, POMC neurons and AgRP neurons project to brain regions likely to be important in regulating body weight (important examples include the paraventricular nucleus and the lateral parabrachial nucleus (Bagnol et al., 1999; Elias et al., 1998; Haskell-Luevano et al., 1999; Wu et al., 2009)).”
Divergence of Melanocortin Pathways in the Control of Food Intake and Energy Expenditure
Balthasar, N., Dalgaard, L. T., Lee, C. E., Yu, J. H., Funahashi, H., Williams, T. B., Ferreira, M. A. R., Tang, V., McGovern, R. A., Kenny, C. D., et al. (2005) · Cell · doi:10.1016/j.cell.2005.08.035 · Cited by 1,122 · see citing works
“First, the PVH receives strong input from proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons, which release the MC4R agonist and antagonist, α-MSH and AgRP, respectively (Bagnol et al., 1999; Cowley et al., 1999).”
BackgroundBrain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor
Xu, B., Goulding, E. H., Zang, K., Cepoi, D., Cone, R. D., Jones, K. R., Tecott, L. H., & Reichardt, L. F. (2003) · Nature Neuroscience · doi:10.1038/nn1073 · Cited by 896 · see citing works
Chen, A. S., Marsh, D. J., Trumbauer, M. E., Frazier, E. G., Guan, X.-M., Yu, H., Rosenblum, C. I., Vongs, A., Feng, Y., Cao, L., et al. (2000) · Nature Genetics · doi:10.1038/79254 · Cited by 896 · see citing works
Multiple neural systems controlling food intake and body weight
Berthoud, H.-R. (2002) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(02)00014-3 · Cited by 725 · see citing works
“[8] Bagnol D, Lu XY, Kaelin CB, Day HE, Ollmann M, Gantz I, Akil H, Barsh GS, Watson SJ.”
BackgroundStudies on the Physiological Functions of the Melanocortin System
Cone, R. D. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0034 · Cited by 615 · see citing works
“POMC and NPY in the arcuate (69), 2) inhibition of the”
BackgroundToward a Wiring Diagram Understanding of Appetite Control
Andermann, M. L., & Lowell, B. B. (2017) · Neuron · doi:10.1016/j.neuron.2017.06.014 · Cited by 606 · see citing works
“ARCPOMC neurons presumably also target the same PVHMC4R neurons (Atasoy et al., 2014; Bagnol et al., 1999; Cowley et al., 1999).”
BackgroundBouret, S. G., Draper, S. J., & Simerly, R. B. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.5369-03.2004 · Cited by 593 · see citing works
“AgRP neurons appear to be limited to the ARH in adult rodents and terminals containing this neuropeptide were found in the DMH, PVH, and LHA of neonatal rats in a pattern that coincides with the innervation of ARH axons (Broberger et al., 1998; Bagnol et al., 1999; Grove et al., 2003).”
BackgroundExpression of melanocortin 4 receptor mRNA in the central nervous system of the rat
Kishi, T., Aschkenasi, C. J., Lee, C. E., Mountjoy, K. G., Saper, C. B., & Elmquist, J. K. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10454 · Cited by 581 · see citing works
Leptin Signaling in the Central Nervous System and the Periphery
Bjørbæk, C. (2004) · Recent Progress in Hormone Research · doi:10.1210/rp.59.1.305 · Cited by 550 · see citing works
“A separate population of cells in the ARC coexpresses two orexigenic peptides, the melanocortin receptor antagonist agouti-related protein (AgRP) and neuropeptide Y (NPY) (Ollmann et al., 1997; Elias et al., 1998; Bagnol et al., 1999; Baskin et al., 1999b; S.C. Chen et al., 1999; Ebihara et al., 1999).”
BackgroundKing, B. M. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.10.007 · Cited by 490 · see citing works
Targeting melanocortin receptors as a novel strategy to control inflammation
Catania, A., Gatti, S., Colombo, G., & Lipton, J. M. (2004) · Pharmacological Reviews · doi:10.1124/pr.56.1.1 · Cited by 438 · see citing works
“Melanocortinergic terminals are found in various hypothalamic regions such as paraventricular, dorsomedial hypothalamic nucleus, arcuate nucleus, and lateral hypothalamic regions (Bagnol et al., 1999).”
BackgroundGenetic approaches to studying energy balance: perception and integration
Barsh, G. S., & Schwartz, M. W. (2002) · Nature Reviews Genetics · doi:10.1038/nrg862 · Cited by 417 · see citing works
Self-citationAgRP(83-132) Acts as an Inverse Agonist on the Human-Melanocortin-4 Receptor
Nijenhuis, W. A. J., Oosterom, J., & Adan, R. A. H. (2001) · Molecular Endocrinology · doi:10.1210/mend.15.1.0578 · Cited by 408 · see citing works
Melanocortin-4 receptor–regulated energy homeostasis
Krashes, M. J., Lowell, B. B., & Garfield, A. S. (2016) · Nature Neuroscience · doi:10.1038/nn.4202 · Cited by 359 · see citing works
The TRH neuron: a hypothalamic integrator of energy metabolism
Lechan, R. M., & Fekete, C. (2006) · Progress in brain research · doi:10.1016/s0079-6123(06)53012-2 · Cited by 338 · see citing works
Münzberg, H., Huo, L., Nillni, E. A., Hollenberg, A. N., & Bjørbæk, C. (2003) · Endocrinology · doi:10.1210/en.2002-221037 · Cited by 328 · see citing works
“Dense concentrations of nerve fibers containing -MSH could be seen in the ARC, DMH, LHA, and many extrahypothalamic brain regions (data not shown), as previously reported (55).”
Hypothalamic nutrient sensing in the control of energy homeostasis
Blouet, C., & Schwartz, G. J. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.12.024 · Cited by 321 · see citing works
“[9] Bagnol D, Lu XY, Kaelin CB, Day HE, Ollmann M, Gantz I, et al.”
BackgroundNew aspects on the melanocortins and their receptors
Wikberg, J. E. S., Muceniece, R., Mandrika, I., Prūsis, P., Lindblom, J., Post, C., & Skottner, A. (2000) · Pharmacological Research · doi:10.1006/phrs.2000.0725 · Cited by 318 · see citing works
The vagus nerve, food intake and obesity
Berthoud, H.-R. (2008) · Regulatory Peptides · doi:10.1016/j.regpep.2007.08.024 · Cited by 316 · see citing works
“[109], oxytocin [110,111], gastrin-releasing peptide (Bombesin) [112], orexin/dynorphin [113], andMCH [114].”
Mandelblat-Cerf, Y., Ramesh, R. N., Burgess, C. R., Patella, P., Yang, Z., Lowell, B. B., & Andermann, M. L. (2015) · eLife · doi:10.7554/elife.07122 · Cited by 290 · see citing works
“DOI: 10.7554/eLife.07122.001”
BackgroundInfluentialAugmentation of drug reward by chronic food restriction
Carr, K. D. (2002) · Physiology & Behavior · doi:10.1016/s0031-9384(02)00759-x · Cited by 300 · see citing works
Whole-brain mapping of the direct inputs and axonal projections of POMC and AgRP neurons
Wang, D., He, X., Zhao, Z., Feng, Q., Lin, R., Sun, Y., Ding, T., Xu, F., Luo, M., & Zhan, C. (2015) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2015.00040 · Cited by 298 · see citing works
“Axonal Projection Patterns of POMC Neurons and AgRP Neurons Previous anterograde tracing and immunocytochemistry labeling have revealed that POMC neurons project to the paraventricular thalamic nucleus (PVT) and several hypothalamic nuclei (Fodor et al., 1998; Bagnol et al., 1999; Cowley et al., 2001).”
BackgroundPro-opiomelanocortin processing in the hypothalamus: impact on melanocortin signalling and obesity
Pritchard, L. E., Turnbull, A. V., & White, A. E. (2002) · Journal of Endocrinology · doi:10.1677/joe.0.1720411 · Cited by 298 · see citing works
“Anatomical evidence for this is supplied by the observation that AGRP and POMC neurons project to identical brain areas (Bagnol et al. 1999).”
Leptin revisited: its mechanism of action and potential for treating diabetes
Coppari, R., & Bjørbæk, C. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3757 · Cited by 295 · see citing works
Noble, E. E., Billington, C. J., Kotz, C. M., & Wang, C. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00776.2010 · Cited by 284 · see citing works
Central regulation of sodium appetite
Geerling, J. C., & Loewy, A. D. (2007) · Experimental Physiology · doi:10.1113/expphysiol.2007.039891 · Cited by 275 · see citing works
“2001a) and receives input from a number of other brain sites, including a dense projection from appetite-stimulatory peptidergic neurones in the arcuate nucleus of the hypothalamus (Bagnol et al. 1999; Shin et al. 2008).”
BackgroundThe role of proopiomelanocortin (POMC) neurones in feeding behaviour
Millington, G. W. (2007) · Nutrition & Metabolism · doi:10.1186/1743-7075-4-18 · Cited by 345 · see citing works
“Again, this may reflect indirect activation, perhaps via an arcuate nucleus POMC neuronal projection to the SON, as evidenced by immunocytochemical detection of POMC fibres between these nuclei and in situ hybridisation for MC3R in the arcuate nucleus and MC4R in the SON (Table 1; [90,93,118]).”
BackgroundMethodInfluentialThe melanocortin pathway and control of appetite-progress and therapeutic implications
Baldini, G., & Phelan, K. D. (2019) · Journal of Endocrinology · doi:10.1530/joe-18-0596 · Cited by 279 · see citing works
Ellacott, K. L. J. (2004) · Recent Progress in Hormone Research · doi:10.1210/rp.59.1.395 · Cited by 262 · see citing works
“that project to identical areas of the brain (Bagnol et al., 1999), the brainstem has few, if any, AgRP-immunoreactive cell bodies and receives limited terminals from the ARC.”
BackgroundInfluentialHaskell‐Luevano, C., & Monck, E. K. (2001) · Regulatory Peptides · doi:10.1016/s0167-0115(01)00234-8 · Cited by 253 · see citing works
Shah, B. P., Vong, L., Olson, D. P., Koda, S., Krashes, M. J., Ye, C., Yang, Z., Fuller, P. M., Elmquist, J. K., & Lowell, B. B. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1407843111 · Cited by 240 · see citing works
“The impetus for focusing on the PVH included the following: (i) MC4R expression is dense in the PVH (10–12), (ii) it receives strong input from AgRP and POMC neurons (13, 14), (iii) injection of MC3/4R ligands into the PVH affects feeding (14–16), (iv) PVH-directed lesions cause obesity (17, 18), and most importantly,…”
BackgroundA rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by α-MSH
Fenselau, H., Campbell, J. N., Verstegen, A. M. J., Madara, J. C., Xu, J., Shah, B. P., Resch, J. M., Yang, Z., Mandelblat-Cerf, Y., Livneh, Y., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4442 · Cited by 233 · see citing works
Lu, X., Barsh, G. S., Akil, H., & Watson, S. J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-21-07863.2003 · Cited by 240 · see citing works
Self-citationBlouet, C., Jo, Y., Li, X., & Schwartz, G. J. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1668-09.2009 · Cited by 240 · see citing works
“In fact, both ARC neurons and their projection targets in the PVN express MC4 receptors (Bagnol et al., 1999; Kishi et al., 2003) and are activated shortly after MBH leucine administration, as evidenced by c-Fos expression and Erk1/2 phosphorylation.”
BackgroundDe Novo Neurogenesis in Adult Hypothalamus as a Compensatory Mechanism to Regulate Energy Balance
Pierce, A. A., & Xu, A. W. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2479-09.2010 · Cited by 224 · see citing works
“The redundant wiring and differential regulation of Pomc and MC4R neurons provide another safeguarding mechanism to ensure sufficient inhibition of anorexigenic drive.”
BackgroundInfluentialBrain-derived neurotrophic factor (BDNF) and food intake regulation: A minireview
Lebrun, B., Bariohay, B., Moyse, E., & Jean, A. (2006) · Autonomic Neuroscience · doi:10.1016/j.autneu.2006.02.027 · Cited by 219 · see citing works
“These two neuronal populations provide overlapping projections to other key parts of the hypothalamus, notably the PVN, DMH, VMH and LHA (Bagnol et al., 1999; Xu et al., 2003).”
BackgroundReizes, O., Lincecum, J. M., Wang, Z., Goldberger, O., Huang, L., Kaksonen, M., Ahima, R. S., Hinkes, M. T., Barsh, G. S., Rauvala, H., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00415-9 · Cited by 212 · see citing works
Self-citationMinireview: Leptin and Development of Hypothalamic Feeding Circuits
Bouret, S. G., & Simerly, R. B. (2004) · Endocrinology · doi:10.1210/en.2004-0231 · Cited by 210 · see citing works
“are generally believed to originate exclusively from NPY containing neurons in the ARH (24, 25).”
Roseberry, A. G., Liu, H., Jackson, A. C., Cai, X., & Friedman, J. M. (2004) · Neuron · doi:10.1016/s0896-6273(04)00074-1 · Cited by 198 · see citing works
Zheng, H., Patterson, L. M., Phifer, C. B., & Berthoud, H. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00869.2004 · Cited by 196 · see citing works
“tion was not significantly changed [F(1, 5) 0.”
Central Serotonin and Melanocortin Pathways Regulating Energy Homeostasis
Heisler, L. K., Cowley, M. A., Kishi, T., Tecott, L. H., Fan, W., Low, M. J., SMART, J. L., Rubinstein, M., Tatro, J. B., Zigman, J. M., et al. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb03177.x · Cited by 187 · see citing works
Body weight is regulated by the brain: a link between feeding and emotion
Kishi, T., & Elmquist, J. K. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001638 · Cited by 178 · see citing works
Beck, B. (2000) · Nutrition · doi:10.1016/s0899-9007(00)00410-x · Cited by 173 · see citing works
Cerdá‐Reverter, J. M., Ringholm, A., Schiöth, H. B., & Peter, R. E. (2003) · Endocrinology · doi:10.1210/en.2002-0213 · Cited by 171 · see citing works
Central regulation of food intake in fish: an evolutionary perspective
Soengas, J. L., Cerdá‐Reverter, J. M., & Delgado, M. J. (2018) · Journal of Molecular Endocrinology · doi:10.1530/jme-17-0320 · Cited by 165 · see citing works
“ARC neurons are the only neurons producing agoutirelated peptide (AgRP) in mice brain (Bangol et al. 1999) thus providing an excellent deterministic clue of the ARC.”
BackgroundThe central melanocortin system regulates food intake in goldfish
Cerdá‐Reverter, J. M., Schiöth, H. B., & Peter, R. E. (2003) · Regulatory Peptides · doi:10.1016/s0167-0115(03)00144-7 · Cited by 159 · see citing works
Abbott, C. R., Rossi, M., Wren, A., Murphy, K. G., Kennedy, A. R., Stanley, S. A., Zollner, A. N., Morgan, D. G. A., Morgan, I., Ghatei, M. A., et al. (2001) · Endocrinology · doi:10.1210/endo.142.8.8304 · Cited by 158 · see citing works
“Such a mechanism has been recently postulated for the melanocortin-3 receptor effect on the melanocortin feeding system (23).”
Hypothalamic regulation of food intake and clinical therapeutic applications
Simpson, K. A., Martin, N. M., & Bloom, S. R. (2009) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302009000200002 · Cited by 157 · see citing works
Small, C. J., Kim, M. S., Stanley, S. A., Mitchell, J. R. D., Murphy, K. G., Morgan, D. G. A., Ghatei, M. A., & Bloom, S. R. (2001) · Diabetes · doi:10.2337/diabetes.50.2.248 · Cited by 156 · see citing works
Neuronal activation in the hypothalamus and brainstem during feeding in rats
Johnstone, L. E., Fong, T. M., & Leng, G. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.08.003 · Cited by 152 · see citing works
Synaptic plasticity in neuronal circuits regulating energy balance
Zeltser, L. M., Seeley, R. J., & Tschöp, M. H. (2012) · Nature Neuroscience · doi:10.1038/nn.3219 · Cited by 147 · see citing works
Cerdá‐Reverter, J. M., & Peter, R. E. (2003) · Endocrinology · doi:10.1210/en.2003-0453 · Cited by 147 · see citing works
60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH
Anderson, E. J. P., Çakır, I., Carrington, S. J. S., Cone, R. D., Ghamari‐Langroudi, M., Gillyard, T. R., Gimenez, L. E., & Litt, M. J. (2016) · Journal of Molecular Endocrinology · doi:10.1530/jme-16-0014 · Cited by 149 · see citing works
“nucleus/area (Bagnol et al. 1999).”
Neuropeptide Y, α-melanocyte–stimulating hormone, and monoamines in food intake regulation
Ramos, E. J. B., Meguid, M. M., Campos, A. C. L., & Coelho, J. C. U. (2005) · Nutrition · doi:10.1016/j.nut.2004.06.021 · Cited by 142 · see citing works
Opioid receptor involvement in the effect of AgRP- (83–132) on food intake and food selection
Hagan, M. M., Rushing, P. A., Benoit, S. C., Woods, S. C., & Seeley, R. J. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.280.3.r814 · Cited by 143 · see citing works
“AgRP is a peptide synthesized in the arcuate nucleus and projects to other key feeding hypothalamic nuclei and sites throughout the brain (2, 19, 26).”
BackgroundLiu, J., Garza, J. C., Truong, H. V., Henschel, J., Zhang, W., & Lu, X.-Y. (2007) · Endocrinology · doi:10.1210/en.2007-0745 · Cited by 141 · see citing works
“Anatomical studies demonstrate that -MSH and AgRP neurons innervate a variety of brain regions that have been well characterized in stress reactions (4).”
BackgroundMethodInfluentialSelf-citationRole of FoxO transcription factors in aging and age-related metabolic and neurodegenerative diseases
Du, S., & Zheng, H. (2021) · Cell & Bioscience · doi:10.1186/s13578-021-00700-7 · Cited by 140 · see citing works
Hypothalamic and vagal neuropeptide circuitries regulating food intake
Broberger, C., & Hökfelt, T. G. M. (2001) · Physiology & Behavior · doi:10.1016/s0031-9384(01)00611-4 · Cited by 139 · see citing works
Autoantibodies against α-MSH, ACTH, and LHRH in anorexia and bulimia nervosa patients
Fetissov, S. O., Hallman, J., Oreland, L., af Klinteberg, B., Grenbäck, E., Hulting, A.-L., & Hökfelt, T. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222658699 · Cited by 140 · see citing works
“The role of melanocortins in body weight regulation: opportunities for the treatment of obesity”
MacNeil, D. J., Howard, A. D., Guan, X.-M., Fong, T. M., Nargund, R. P., Bednarek, M. A., Goulet, M. T., Weinberg, D. H., Strack, A. M., Marsh, D. J., et al. (2002) · European Journal of Pharmacology · doi:10.1016/s0014-2999(02)01989-1 · Cited by 137 · see citing works
Song, Y., Golling, G., Thacker, T. L., & Cone, R. D. (2003) · Endocrine · doi:10.1385/endo:22:3:257 · Cited by 137 · see citing works
CART in the regulation of appetite and energy homeostasis
Lau, J., & Herzog, H. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00313 · Cited by 138 · see citing works
“POMC/CART neurons express the melanocortin 3-receptor (MC3-R) which is specific for melanocortin peptides derived from the posttranslational cleavage of POMC (Bagnol et al., 1999), such as the anorectic α-MSH (Fan et al., 1997; Huszar, 1997; Kim et al., 2000; Zheng et al., 2005).”
BackgroundResultInfluentialZheng, H., Corkern, M., Stoyanova, I., Patterson, L. M., Tian, R., & Berthoud, H.-R. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00781.2002 · Cited by 135 · see citing works
“hypothalamic and many extrahypothalamic areas (1,33,34), Both α-MSH and CART-peptide have been”
BackgroundInfluentialRole of central melanocortin pathways in energy homeostasis
Garfield, A. S., Lam, D. D., Marston, O. J., Przydzial, M. J., & Heisler, L. K. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2009.02.002 · Cited by 135 · see citing works
Differential Role of Melanocortin Receptor Subtypes in Cachexia
Marks, D. L., Butler, A. A., Turner, R. J., Brookhart, G., & Cone, R. D. (2003) · Endocrinology · doi:10.1210/en.2002-221099 · Cited by 134 · see citing works
Neural melanocortin receptors in obesity and related metabolic disorders
Girardet, C., & Butler, A. A. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.05.004 · Cited by 128 · see citing works
“The largest population is located in the hypothalamus, and more specifically in the lateral part of the ARC.”
InfluentialInvestigation of the melanocyte stimulating hormones on food intake
Abbott, C. R., Rossi, M., Kim, M.-S., AlAhmed, S. H., Taylor, G. M., Ghatei, M. A., Smith, D. M., & Bloom, S. R. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02386-6 · Cited by 127 · see citing works
The Melanocortin-3 Receptor Is Required for Entrainment to Meal Intake
Sutton, G. M., Pérez–Tilve, D., Nogueiras, R., Fang, J., Kim, J. K., Cone, R. D., Gimble, J. M., Tschöp, M. H., & Butler, A. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3615-08.2008 · Cited by 128 · see citing works
“Pomc and AgRP neurons innervate hypothalamic areas involved in entrainment of anticipatory behaviors to feeding (Bagnol et al., 1999; Haskell-Luevano et al., 1999; Singru et al., 2007).”
BackgroundKishi, T., Aschkenasi, C. J., Choi, B. J., Lopez, M. E., Lee, C. E., Liu, H., Hollenberg, A. N., Friedman, J. M., & Elmquist, J. K. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20432 · Cited by 119 · see citing works
“The PVH receives dense -MSH and AgRP inputs from the Arc in the rat (Jacobowitz and O’donohue, 1978; Bagnol et al., 1999; Haskell-Luevano et al., 1999) and mouse (Broberger et al., 1998b).”
BackgroundInputs to the ventrolateral bed nucleus of the stria terminalis
Shin, J., Geerling, J. C., & Loewy, A. D. (2008) · Journal of Comparative Neurology · doi:10.1002/cne.21870 · Cited by 115 · see citing works
“…AgRP immunoreactivity was also found in neuronal somata only within the medial subregion of the arcuate hypothalamic nucleus, again consistent with previous in situ hybridization and immunohistochemical findings (Broberger et al., 1998; Elias et al., 1998b; Hahn et al., 1998; Bagnol et al., 1999).”
ResultThe regulation of food intake by selective stimulation of the type 3 melanocortin receptor (MC3R)
Marks, D. L., Hruby, V. J., Brookhart, G., & Cone, R. D. (2005) · Peptides · doi:10.1016/j.peptides.2005.01.025 · Cited by 116 · see citing works
“Several lines of evidence suggest that γ-MSH acts on the MC3R within the hypothalamic arcuate nucleus to dampen the activity of arcuate POMC neurons via direct and indirect neural mechanisms [1,10,29,31].”
BackgroundInvolvement of melanocortin-4 receptor in anxiety and depression
Chaki, S., & Okuyama, S. (2005) · Peptides · doi:10.1016/j.peptides.2004.11.029 · Cited by 116 · see citing works
Wirth, M. M., Olszewski, P. K., Yu, C., Levine, A. S., & Giraudo, S. Q. (2001) · Peptides · doi:10.1016/s0196-9781(00)00367-3 · Cited by 115 · see citing works
Distribution and Function of Melanocortin Receptors within the Brain
Mountjoy, K. G. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-6354-3_3 · Cited by 114 · see citing works
Creemers, J. W. M., Pritchard, L. E., Gyte, A., Rouzic, P. L., Meulemans, S. M. P., Wardlaw, S. L., Zhu, X., Steiner, D. F., Davies, N., Armstrong, D., et al. (2005) · Endocrinology · doi:10.1210/en.2005-1373 · Cited by 112 · see citing works
Functions for pro-opiomelanocortin-derived peptides in obesity and diabetes
Mountjoy, K. G. (2010) · Biochemical Journal · doi:10.1042/bj20091957 · Cited by 108 · see citing works
Cognitive and autonomic determinants of energy homeostasis in obesity
Richard, D. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.103 · Cited by 109 · see citing works
Cerdá‐Reverter, J. M., Agulleiro, M. J., Guillot, R., Sánchez, E., Ceinos, R. M., & Rotllant, J. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.10.108 · Cited by 105 · see citing works
“In rodents, two discrete groups of neurons in the hypothalamus (arcuate nucleus) and the medulla (nucleus of the tractus solitarius) also produce POMC (Bangol et al., 1999).”
BackgroundSleep Deprivation and Central Appetite Regulation
Liu, S., Wang, X., Zheng, Q., Gao, L., & Sun, Q. (2022) · Nutrients · doi:10.3390/nu14245196 · Cited by 111 · see citing works
“This loop is composed of appetite-suppressing POMC neurons in the hypothalamic arcuate nucleus, appetite-promoting AgRP neurons, melanocortin receptor-4 (MC4R)-positive neurons in the paraventricular nucleus, and the neural projections between them [46].”
BackgroundWilliams, D. L., Bowers, R. R., Bartness, T. J., Kaplan, J. M., & Grill, H. J. (2003) · Endocrinology · doi:10.1210/en.2003-0440 · Cited by 104 · see citing works
Melanocortin‐3 Receptor mRNA Expression in Pro‐Opiomelanocortin Neurones of the Rat Arcuate Nucleus
Jégou, S., Boutelet, I., & Vaudry, H. (2000) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2000.00477.x · Cited by 101 · see citing works
Wang, C., Bomberg, E. M., Levine, A. S., Billington, C. J., & Kotz, C. M. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00125.2007 · Cited by 99 · see citing works
“6, A and B), indicating that BDNF in the VMH reduces feeding and body weight gain via its receptor TrkB. ARC NPY neurons project to other areas of the hypothalamus, including the PVN and VMH. NPY has been reported to increase feeding not only after administration into the PVN but also after VMH injection (5, 9, 24, 31…”
BackgroundPathophysiology and treatment of inflammatory anorexia in chronic disease
Braun, T. P., & Marks, D. L. (2010) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1007/s13539-010-0015-1 · Cited by 99 · see citing works
“Importantly, α-MSH and AgRP immunoreactive fibers project to many of the same locations across the CNS, although AgRP projections are less dense [81–83].”
BackgroundBrain effects of melanocortins☆
BERTOLINI, A., Tacchi, R., & Vergoni, A. V. (2008) · Pharmacological Research · doi:10.1016/j.phrs.2008.10.005 · Cited by 98 · see citing works
Watts, A. G. (2000) · Hormones and Behavior · doi:10.1006/hbeh.2000.1581 · Cited by 98 · see citing works
Fekete, C., Singru, P. S., Sanchez, E., Sarkar, S., Christoffolete, M. A., Riberio, R. S., Rand, W. M., Emerson, C. H., Bianco, A. C., & Lechan, R. M. (2006) · Endocrinology · doi:10.1210/en.2005-0956 · Cited by 97 · see citing works
Adan, R. A. H., & Kas, M. J. (2003) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(03)00130-5 · Cited by 97 · see citing works
Chisada, S., Kurokawa, T., Murashita, K., Rønnestad, I., Taniguchi, Y., Toyoda, A., Sakaki, Y., Takeda, S., & Yoshiura, Y. (2013) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2013.10.008 · Cited by 96 · see citing works
Fang, X., Jiang, S., Wang, J., Bai, Y., Kim, C. S., Blake, D., Weintraub, N. L., Lei, Y., & Lu, X.-Y. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-01004-x · Cited by 95 · see citing works
Self-citationMercer, J. G., Moar, K. M., Logie, T. J., Findlay, P. A., Adam, C. L., & Morgan, P. J. (2001) · Endocrinology · doi:10.1210/endo.142.10.8454 · Cited by 94 · see citing works
Central and peripheral control of food intake
Abdalla, M. M. I. (2017) · Endocrine Regulations · doi:10.1515/enr-2017-0006 · Cited by 92 · see citing works
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 · see citing works
The Central Nervous System Sites Mediating the Orexigenic Actions of Ghrelin
Mason, B. L., Wang, Q., & Zigman, J. M. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170310 · Cited by 89 · see citing works
Hagan, M. M., Benoit, S. C., Rushing, P. A., Pritchard, L. M., Woods, S. C., & Seeley, R. J. (2001) · Endocrinology · doi:10.1210/endo.142.3.8018 · Cited by 90 · see citing works
Hypothalamic Melanocortin System Regulates Sympathetic Nerve Activity in Brown Adipose Tissue
Yasuda, T., Masaki, T., Kakuma, T., & Yoshimatsu, H. (2004) · Experimental Biology and Medicine · doi:10.1177/153537020422900303 · Cited by 89 · see citing works
Responsiveness to Peripherally Administered Melanocortins in Lean and Obese Mice
Blüher, S., Ziotopoulou, M., Bullen, J. W., Moschos, S. J., Ungsunan, L., Kokkotou, E. G., Maratos–Flier, E., & Mantzoros, C. S. (2004) · Diabetes · doi:10.2337/diabetes.53.1.82 · Cited by 89 · see citing works
Wittmann, G., Hrabovszky, E., & Lechan, R. M. (2013) · The Journal of Comparative Neurology · doi:10.1002/cne.23350 · Cited by 87 · see citing works
“Hypothalamic POMC neurons project to a wide variety of brain regions (Bagnol et al., 1999; Haskell-Luevano et al., 1999), and it has been suggested that subpopulations of POMC neurons innervate distinct target sites (King and Hentges, 2011).”
Background
- Authors
- Bagnol, D., Lu, X.-Y., Kaelin, C. B., Day, H. E. W., Ollmann, M., Gantz, I., Akil, H., Barsh, G. S., & Watson, S. J.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Mental Health Research Institute (AU)
- Howard Hughes Medical Institute (US)
- University of Michigan (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-09-15
- Volume
- 19
- Issue
- 18
- Pages
- RC26-RC26
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6782481
- OpenAlex
- W1572502886
- Cited by
- 425
- References
- 29
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 15 · 2023: 11 · 2022: 11 · 2021: 12 · 2020: 10 · 2019: 11 · 2018: 14 · 2017: 12 · 2016: 14 · 2015: 20 · 2014: 9 · 2013: 16 · 2012: 18
- FWCI
- 6.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (P01 MH 42251, P01MH042251)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK-54032-01, R01DK054032, DK 28506)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- agouti-related protein, proopiomelanocortin, melanocortin 3 receptor, melanocortin-4 receptor, melanocortin signaling, orexigenic peptides, product inhibition, neuroanatomy, feeding behavior
- MeSH terms
- Animals, Autoradiography, Brain, Immunohistochemistry, Male, Nerve Fibers, Pro-Opiomelanocortin, Proteins, Rats, Sprague-Dawley, In Situ Hybridization, Receptors, Corticotropin, Intercellular Signaling Peptides and Proteins, Receptor, Melanocortin, Type 3, Receptor, Melanocortin, Type 4, Rats, Agouti-Related Protein
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