Cited by 580Regulation of Appetite and ObesityNeuropeptides and Animal PhysiologyHypothalamic control of reproductive hormones

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A C-Terminal Fragment of Agouti-Related Protein Increases Feeding and Antagonizes the Effect of Alpha-Melanocyte Stimulating Hormone in Vivo

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., Smith, D. M., Yagaloff, K., Ghatei, M. A., Bloom, S. R.·1998·Endocrinology

DOI 10.1210/endo.139.10.6332

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Abstract

Agouti-related protein (Agrp) is present in rat and human hypothalamus and is structurally related to agouti protein. Overexpression of either of these proteins results in obesity. However the effect of exogenous Agrp and its in vivo interaction with alpha-melanocyte stimulating hormone (alphaMSH), the likely endogenous melanocortin 3 and 4 receptor (MC3-R and MC4-R) agonist, have not been demonstrated. We report that 1 nmol of Agrp(83-132), a C-terminal fragment of Agrp, when administered intracerebroventricularly (ICV) into rats, increased food intake over a 24-h period (23.0+/-1.4 g saline vs 32.9+/-2.3 g Agrp, p<0.05). The hyperphagia was similar to that seen when 1 nmol of the synthetic MC3-R and MC4-R antagonist SHU9119 was given i.c.v. (19.6+/-1.8 g saline vs 32.5+/-1.7 g SHU9119, p<0.001). Both Agrp(83-132) and SHU9119 blocked the reduction in 1-h food intake of i.c.v. alphaMSH at the beginning of the dark phase. This effect occurred independently of whether the antagonists were administered simultaneously, or nine hours prior, to the alphaMSH. We have also shown Agrp(83-132) is an antagonist at the MC3-R and MC4-R, with similar inhibition of cAMP activation to that previously reported for the full length peptide. In conclusion, Agrp(83-132) administered i.c.v. increases feeding with long lasting effects and is able to inhibit the action of alphaMSH. This interaction may be mediated by the MC3-R and/or MC4-R.

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Items 201–300 of 580

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“Neuropeptide Y (NPY) and agouti-related protein (AgRP) are traditionally classified as food-stimulating neuropeptides and are highly co-expressed neuropeptides in arcuate nucleus neurons (Stanley & Leibowitz 1985, Morley et al. 1987, Hahn et al. 1998, Rossi et al. 1998, Hagan et al. 2000).”
Background
Dissecting the role of cocaine- and amphetamine-regulated transcript (CART) in the control of appetite
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“The central administration of AGRP (Rossi et al., 1998) or synthetic melanocortins (Kask et al.”
Background
Melanocortin 4 Receptor Becomes an ACTH Receptor by Coexpression of Melanocortin Receptor Accessory Protein 2
Agulleiro, M. J., Cortés, R., Fernández-Durán, B., Navarro, S., Guillot, R., Meimaridou, E., Clark, A., & Cerdá‐Reverter, J. M. (2013) · Molecular Endocrinology · doi:10.1210/me.2013-1099 · Cited by 64
“A similar metabolic syndrome is also observed in transgenic mice ubiquitously overexpressing AGRP (9), and in MC4R-knockout mice (7).”
BackgroundInfluential
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Strader, A. D., Schiöth, H. B., & Buntin, J. D. (2003) · Brain Research · doi:10.1016/s0006-8993(02)03799-x · Cited by 64
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Hypothalamic control of feeding
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Self-citation
Central administration of neuropeptide Y induces wakefulness in rats
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“All these neuropeptides stimulate food intake when injected into the cerebral ventricle or into various hypothalamic nuclei (9; 20; 34-36; 46).”
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“By contrast, MC4-R blockade with a C-terminal fragment (residues 83–132) of the endogenous receptor antagonist agouti-related peptide (AGRP) increases food intake following intracerebroventricular injection (Rossi et al., 1998).”
Background
Hindbrain catecholamine neurons mediate consummatory responses to glucoprivation
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Background
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“In rats, central injection of NPY, AGRP and GHRH increases food intake, whereas central injection of α-melanocyte-stimulating hormone (α-MSH), an end product of POMC processing, decreases food intake [31,32].”
Background
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Clarke, I. J., Rao, A., Chilliard, Y., Delavaud, C., & Lincoln, G. A. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00424.2002 · Cited by 60
“By preventing the inhibitory action of -MSH on VFI, AGRP may act as a stimulator of appetite (74).”
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“Furthermore, the C-terminal fragment itself shows an orexigenic effect when administered centrally (Rossi et al., 1998).”
Background
Dynorphin A1–17-Induced Feeding: Pharmacological Characterization Using Selective Opioid Antagonists and Antisense Probes in Rats
Silva, R. M., Grossman, H. C., Hadjimarkou, M. M., Rossi, G. C., Pasternak, G. W., & Bodnar, R. J. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.301.2.513 · Cited by 58
Central Melanocortin Receptors Mediate Changes in Food Intake in the Rhesus Macaque
Koegler, F. H., Grove, K. L., Schiffmacher, A. T., Smith, M. S., & Cameron, J. L. (2001) · Endocrinology · doi:10.1210/endo.142.6.8198 · Cited by 57
“This fragment of AGRP peptide is known to be biologically active ( 15 ).”
Background
The anorexic effect of alpha-melanocyte-stimulating hormone is mediated by corticotrophin-releasing factor in chicks
Tachibana, T., Oikawa, D., Takahashi, H., Boswell, T. C., & Furuse, M. (2007) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2006.12.044 · Cited by 57
Stochastic neuropeptide signals compete to calibrate the rate of satiation
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Molecular connectomics reveals a glucagon-like peptide 1-sensitive neural circuit for satiety
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“Besides the central appetite-suppressing (anorexigenic) effect of α-MSH [14], melanocortins increase the metabolic rate mediated by peripheral cells expressing different melanocortin receptors such as muscle cells, expressing MC1R, MC3R, MC4R, and especially MC5R [15,16].”
Background
The orally active melanocortin-4 receptor antagonist BL-6020/979: a promising candidate for the treatment of cancer cachexia
Dallmann, R., Weyermann, P., Anklin, C., Boroff, M., Bray‐French, K., Cardel, B., Courdier-Fruh, I., Deppe, H., Dubach‐Powell, J., Erb, M., et al. (2011) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1007/s13539-011-0039-1 · Cited by 55
“Agouti-related protein (AgRP) is an endogenous antagonist at the MC-4R and has been shown to increase food intake and reduce energy expenditure [12–15].”
Background
Programming of the Appetite‐Regulating Neural Network: A Link Between Maternal Overnutrition and the Programming of Obesity?
Mühlhäusler, B. S. (2006) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2006.01505.x · Cited by 55
Cocaine- and amphetamine-regulated transcript, glucagon-like peptide-1 and corticotrophin releasing factor inhibit feeding via agouti-related protein independent pathways in the rat
Edwards, C. M. B., Abbott, C. R., Sunter, D., Kim, M.-S., Dakin, C. L., Murphy, K. G., Abusnana, S., Taheri, S., Rossi, M., & Bloom, S. R. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02257-5 · Cited by 59
Self-citation
The role of melanocortin-3 and -4 receptor in regulating appetite, energy homeostasis and neuroendocrine function in the pig
Barb, C. R., Robertson, A., Barrett, J., Kraeling, R. R., & Houseknecht, K. (2004) · Journal of Endocrinology · doi:10.1677/joe.0.1810039 · Cited by 55
“A structure and function relationship has been observed in natural and experimentally induced MC-R mutations in humans (Valverde et al. 1995, Frandberg et al. 1997) and mice ( Robbins et al. 1993 ).”
Background
Agouti-Related Protein Stimulates the Hypothalamic-Pituitary-Adrenal (HPA) Axis and Enhances the HPA Response to Interleukin-1 in the Primate
Xiao, E., Xia‐Zhang, L., Vulliémoz, N. R., Ferin, M., & Wardlaw, S. L. (2003) · Endocrinology · doi:10.1210/en.2002-220013 · Cited by 53
“strated in the monkey as well as in the rodent (10, 11).”
Background
Effect of central administration of prolactin-releasing peptide on feeding in chicks
Tachibana, T., Saito, S., Tomonaga, S., Takagi, T., Saito, E.-S., Nakanishi, T., Koutoku, T., Tsukada, A., Ohkubo, T., Boswell, T. C., et al. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2003.12.005 · Cited by 54
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Effects of pro-opiomelanocortin (POMC) on food intake and body weight: mechanisms and therapeutic potential?
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Combined Blockade of Both μ- and κ-Opioid Receptors Prevents the Acute Orexigenic Action ofAgouti-Related Protein
Brugman, S., Clegg, D. J., Woods, S. C., & Seeley, R. J. (2002) · Endocrinology · doi:10.1210/en.2002-220230 · Cited by 53
Plasma Agouti‐Related Protein Level: A Possible Correlation with Fasted and Fed States in Humans and Rats
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Characterization, tissue distribution and regulation of agouti-related protein (AgRP) in a cyprinid fish (Schizothorax prenanti)
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Acute heat stress up-regulates neuropeptide Y precursor mRNA expression and alters brain and plasma concentrations of free amino acids in chicks
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Mechanism of Action of Acupuncture in Obesity: A Perspective From the Hypothalamus
Wang, L., Yu, C.-C., Li, J., Tian, Q., & Du, Y. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.632324 · Cited by 55
Neuropeptide Y, but Not Agouti-Related Peptide or Melanin-Concentrating Hormone, Is a Target Peptide for Orexin-A Feeding Actions in the Rat Hypothalamus
López, M., Seoane, L. M., Garcia, M. D. C., Diéguez, C., & Señarís, R. M. (2002) · Neuroendocrinology · doi:10.1159/000048219 · Cited by 52
The regulation of body weight: lessons from the seasonal animal
Morgan, P. J., & Mercer, J. G. (2001) · Proceedings of The Nutrition Society · doi:10.1079/pns200060 · Cited by 52
“Both overexpression of AgRP and intracerebroventricular administration results in hyperphagia (Shutter et al. 1997; Rossi et al. 1998), consistent with its role as an orexigenic signal.”
Background
MTII-induced reduction of voluntary ethanol drinking is blocked by pretreatment with AgRP-(83–132)
Navarro, M., Cubero, I., Knapp, D. J., & Thiele, T. E. (2003) · Neuropeptides · doi:10.1016/j.npep.2003.10.003 · Cited by 51
Time course of short-term and long-term orexigenic effects of Agouti-related protein (86-132)
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Central and peripheral neuroendocrine peptides and signalling in appetite regulation: considerations for obesity pharmacotherapy
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“Agouti-related protein (AgRP) Overexpression of central AgRP results in obesity; intracerebroventricular administration of AgRP (83–132) increases feeding with long-lasting effects while inhibiting the action of alpha-MSH (15).”
Uneven balance of power between hypothalamic peptidergic neurons in the control of feeding
Wei, Q., Krolewski, D. M., Moore, S. J., Kumar, V., Li, F. R., Martin, B., Tomer, R., Murphy, G. G., Deisseroth, K. A., Watson, S. J., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1802237115 · Cited by 49
Agouti-related protein(83-132) aggregates and crosses the blood-brain barrier slowly
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Differential expression of cocaine- and amphetamine-regulated transcript and agouti related-protein in chronically food-restricted sheep
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Self-citation
Central Melanocortins Regulate the Motivation for Sucrose Reward
Pandit, R., van der Zwaal, E. M., Luijendijk, M. C. M., Brans, M. A. D., van Rozen, A. J., Ophuis, R. J. A. O., Vanderschuren, L. J. M. J., Adan, R. A. H., & la Fleur, S. E. (2015) · PLoS ONE · doi:10.1371/journal.pone.0121768 · Cited by 48
“In line with these observations, central infusion of α -MSH or its cyclic analogue MTII robustly suppresses food intake [9;10], whereas treatment with AGRP or the MC3/4 receptor antagonist SHU9119 has the opposite effect [9;11].”
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“Male B6 mice were administered AgRP82–131 (0.05 nmol/d), which is an antagonist/inverse agonist at the Mc3r and Mc4r (33, 34), or acsf for 14 d as described previously (22).”
MethodInfluential
AgRP(83–132) and SHU9119 differently affect activity-based anorexia
Hillebrand, J. J., Kas, M. J., Scheurink, A. J. W., van Dijk, G., & Adan, R. A. H. (2005) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2005.11.004 · Cited by 49
“The long-lasting hyperphagic response of AgRP (83—132) is observed in ad libitum fed rats as well as food-restricted rats (Rossi et al., 1998; Wirth and Giraudo, 2000), however, the long-lasting hyperphagic response of SHU9119 (Fan et al., 1997) is absent in food-restricted or food-deprived rats…”
Chronic Application of MTII in a Rat Model of Obesity Results in Sustained Weight Loss
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The melanocortin antagonist AgRP (83–132) increases appetitive responding for a fat, but not a carbohydrate, reinforcer
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“These ideas are consistent with previous work demonstrating the capacity of AgRP to increase intake of standard lab chow, which is composed primarily of carbohydrates and is generally presented as the only available food source (Rossi et al., 1998, Hagan et al., 2001).”
BackgroundResult
A Treasure Trove of Hypothalamic Neurocircuitries Governing Body Weight Homeostasis
Vianna, C. R., & Coppari, R. (2010) · Endocrinology · doi:10.1210/en.2010-0778 · Cited by 51
Evidence of interactions between melanocortin and opioid systems in regulation of feeding
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Agouti-related protein increases food hoarding more than food intake in Siberian hamsters
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Sustained orexigenic effect of Agouti related protein may be not mediated by the melanocortin 4 receptor
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Self-citation
Moderate high fat diet increases sucrose self-administration in young rats
Figlewicz, D. P., Jay, J. L., Acheson, M. A., Magrisso, I. J., West, C. H., Zavosh, A., Benoit, S. C., & Davis, J. F. (2012) · Appetite · doi:10.1016/j.appet.2012.09.021 · Cited by 46
Regulation of appetite to treat obesity
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Leptin, diabetes, and the brain
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“[84] Both NPY and AgRP promote weight gain[85,86] and insulin resistance[87,88] and, in contrast to POMC neurons, these NPY/AgRP neurons are inhibited by leptin.”
Background
Potential relationship between dietary long-chain saturated fatty acids and hypothalamic dysfunction in obesity
Sergi, D., & Williams, L. M. (2019) · Nutrition Reviews · doi:10.1093/nutrit/nuz056 · Cited by 48
Interrelationships between μ opioid and melanocortin receptors in mediating food intake in rats
Grossman, H. C., Hadjimarkou, M. M., Silva, R. M., Giraudo, S. Q., & Bodnar, R. J. (2003) · Brain Research · doi:10.1016/s0006-8993(03)03442-5 · Cited by 46
Feeding response to melanocortin agonist predicts preference for and obesity from a high-fat diet
Chandler-Laney, P. C., Viana, J. B., Oswald, K. D., Wauford, P. K., & Boggiano, M. M. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.04.011 · Cited by 45
“Agouti-related peptide (AgRP), the MC antagonist, increases food intake and body weight [22,23].”
Background
Functional Heterogeneity of Arcuate Nucleus Pro-Opiomelanocortin Neurons: Implications for Diverging Melanocortin Pathways
Sohn, J., & Williams, K. W. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8240-6 · Cited by 46
“rons activates MC3Rs and MC4Rs and results in a potent inhibition of food intake [5–8].”
Agouti-Related Protein Antagonizes Glucocorticoid Production Induced through Melanocortin 4 Receptor Activation in Bovine Adrenal Cells: A Possible Autocrine Control
Doghman, M., Delagrange, P., Blondet, A., Berthelon, M., Durand, P., Naville, D., & Bégeot, M. (2003) · Endocrinology · doi:10.1210/en.2003-0605 · Cited by 44
“Agrp or its active (83–132) C-terminal fragment have been shown to strongly antagonize MSH at the level of MC3-R and MC4-R in hypothalamus, resulting in an increase on appetite and food intake (5).”
Background
Circadian regulation of appetite and time restricted feeding
Page, A. J., Christie, S., Symonds, E. L., & Li, H. (2020) · Physiology & Behavior · doi:10.1016/j.physbeh.2020.112873 · Cited by 44
Arcuate nucleus of hypothalamus is involved in mediating the satiety effect of electroacupuncture in obese rats
Wang, F., Tian, D., Tso, P., & Han, J. S. (2011) · Peptides · doi:10.1016/j.peptides.2011.10.019 · Cited by 44
Alpha-Melanocyte-Stimulating Hormone-Mediated Appetite Regulation in the Central Nervous System
Wu, Q., Chen, J., Hua, T., & Cai, J. (2023) · Neuroendocrinology · doi:10.1159/000530804 · Cited by 46
Structure−Activity Relationship of (1-Aryl-2-piperazinylethyl)piperazines: Antagonists for the AGRP/Melanocortin Receptor Binding
Arasasingham, P. N., Fotsch, C. H., Ouyang, X., Norman, M. H., Kelly, M. G., Stark, K. L., Karbon, B., Hale, C., Baumgartner, J. W., Zambrano, M., et al. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm0255522 · Cited by 43
A Role for the Agouti-Related Protein Promoter in Obesity and Type 2 Diabetes
Mayfield, D. K., Brown, A. M., Page, G. P., Garvey, W. T., Shriver, M. D., & Argyropoulos, G. A. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5600 · Cited by 43
Can neuropeptides treat obesity? A review of neuropeptides and their potential role in the treatment of obesity
Boughton, C. K., & Murphy, K. G. (2012) · British Journal of Pharmacology · doi:10.1111/bph.12037 · Cited by 45
“Central injection of AgRP increases food intake by blocking the anorectic effect of a-MSH at MC4 receptors (Rossi et al., 1998), and transgenic mice overexpressing AgRP have a similar phenotype to MC4 receptor knockout mice (Graham et al., 1997; Ollmann et al., 1997).”
Background
Agouti-related peptide prevents steroid-induced luteinizing hormone and prolactin surges in female rats
Schiöth, H. B., Kakizaki, Y., Kohsaka, A., Suda, T., & Watanobe, H. (2001) · Neuroreport · doi:10.1097/00001756-200103260-00014 · Cited by 42
Inhibition of Agouti-Related Peptide Expression by Glucose in a Clonal Hypothalamic Neuronal Cell Line Is Mediated by Glycolysis, Not Oxidative Phosphorylation
Cheng, H., Isoda, F., Belsham, D. D., & Mobbs, C. V. (2007) · Endocrinology · doi:10.1210/en.2007-0772 · Cited by 42
“AgRP causes increased food intake and weight gain (4), and”
Background
Regulation of leptin by agouti
Claycombe, K., Xue, B., Mynatt, R. L., Zemel, M. B., & Moustaïd‐Moussa, N. (2000) · Physiological Genomics · doi:10.1152/physiolgenomics.2000.2.3.101 · Cited by 40
“Pro-opiomelanocortin (POMC) serves as a precursor to a-MSH which is an endogenous ligand for melanocortin receptors 3 and 4 (MC3-R and MC4-R) in the hypothalamus (18, 26).”
BackgroundInfluential
The Anorexigenic Fatty Acid Synthase Inhibitor, C75, Is a Nonspecific Neuronal Activator
Takahashi, K. A., Smart, J. L., Liu, H., & Cone, R. D. (2003) · Endocrinology · doi:10.1210/en.2003-0337 · Cited by 42
Astrocytes: new targets of melanocortin 4 receptor actions
Caruso, C. M., Carniglia, L., Durand, D., Scimonelli, T. N., & Lasaga, M. (2013) · Journal of Molecular Endocrinology · doi:10.1530/jme-13-0064 · Cited by 42
Melanocortin neurons: Multiple routes to regulation of metabolism
Shen, W.-J., Yao, T. S., Kong, X., Williams, K. W., & Liu, T. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.05.007 · Cited by 45
FAS inhibitor cerulenin reduces food intake and melanocortin receptor gene expression without modulating the other (an)orexigenic neuropeptides in chickens
Dridi, S., Ververken, C., Hillgartner, F. B., Arckens, L., der Gucht, E. V., Cnops, L., Decuypere, E. M. P., & Buyse, J. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00899.2005 · Cited by 41
NPY-induced feeding: pharmacological characterization using selective opioid antagonists and antisense probes in rats
Israel, Y., Kandov, Y., Khaimova, E., Kest, A., Lewis, S. R., Pasternak, G. W., Pan, Y., Rossi, G. C., & Bodnar, R. J. (2005) · Peptides · doi:10.1016/j.peptides.2005.01.017 · Cited by 41
The biosynthesis and processing of neuropeptides: lessons from prothyrotropin releasing hormone (proTRH)
Perelló, M. (2007) · Frontiers in bioscience · doi:10.2741/2334 · Cited by 38
“AgRP acts as a competitive antagonist or inverse agonist on the melanocortin receptors (73, 74), and blocks -MSHinduced effects on TRH release (75).”
Background
Melanocortin-3 Receptors and Metabolic Homeostasis
Begriche, K., Clemence, G., McDonald, P. H., & Butler, A. A. (2013) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-386933-3.00004-2 · Cited by 42
Behind melanocortin antagonist overexpression in the zebrafish brain: A behavioral and transcriptomic approach
Guillot, R., Cortés, R., Navarro, S., Mischitelli, M., García-Herranz, V., Sánchez, E., Cal, L., Navarro, J. C., Míguez, J. M., Afanasyev, S., et al. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.04.011 · Cited by 39
“fragment of AGRP (Rossi et al., 1998) or chemical antagonists for MC3R and MC4R increase food”
Agouti-related protein (83-132) is a competitive antagonist at the human melanocortin-4 receptor: no evidence for differential interactions with pro-opiomelanocortin-derived ligands
Pritchard, L. E., Armstrong, D., Davies, N., Oliver, R. L., Schmitz, C., Brennand, J. C., Wilkinson, G. H., & White, A. E. (2004) · Journal of Endocrinology · doi:10.1677/joe.0.1800183 · Cited by 40
“Moreover, the AGRP C-terminal domain is alone capable of exerting potent effects on energy balance in vivo (Rossi et al. 1998).”
Background
Neuropeptide W: An Anorectic Peptide Regulated by Leptin and Metabolic State
Date, Y., Mondal, M. S., Kageyama, H., Ghamari‐Langroudi, M., Takenoya, F., Yamaguchi, H., Shimomura, Y., Mori, M., Murakami, N., Shioda, S., et al. (2010) · Endocrinology · doi:10.1210/en.2009-1153 · Cited by 39
“The binding of ANPW23-C to biotinylated [(1)Cys] human NPW-[11-23] was efficiently inhibited by rat NPW23 in dose-dependent manner, whereas both of rat NPW30 and neuropeptide B did not inhibit the binding.”
BackgroundMethod
A Role for Agouti-Related Protein in Appetite Regulation in a Species with Continuous Nutrient Delivery
Wagner, C. G., McMahon, C. D., Marks, D. L., Daniel, J. A., Steele, B., & Sartin, J. L. (2004) · Neuroendocrinology · doi:10.1159/000082735 · Cited by 39
Agouti-related protein in patients with acute and weight-restored anorexia nervosa
Merle, J. V., Haas, V. K., Burghardt, R., Döhler, N., Schneider, N., Lehmkuhl, U., & Ehrlich, S. (2011) · Psychological Medicine · doi:10.1017/s0033291711000365 · Cited by 39
Peripherally administered [Nle4, d -Phe7]-α-melanocyte stimulating hormone increases resting metabolic rate, while peripheral agouti-related protein has no effect, in wild type C57BL/6 and ob/ob mice
Hoggard, N., Rayner, D. V., Johnston, S. L., & Speakman, J. R. (2004) · Journal of Molecular Endocrinology · doi:10.1677/jme.1.01632 · Cited by 39
“Central nervous system (CNS) administration of MSH or MTII (both MC4R agonists) decreases food intake and body weight (Rossi et al. 1998, Barsh 1999).”
Background
Resolving Behavioral Output via Chemogenetic Designer Receptors Exclusively Activated by Designer Drugs
Burnett, C. J., & Krashes, M. J. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.1333-16.2016 · Cited by 40
“…was attributed to the role of the fast-acting neurotransmitter GABA and/or NPY, while AgRP was capable of promoting food intake over an extended period of time (Krashes et al., 2013), supporting previous pharmacology studies (Clark et al., 1984; Rossi et al., 1998; Semjonous et al., 2009).”
Result
Leptin and melanocortin signaling in the hypothalamus
Bjørbæk, C., & Hollenberg, A. N. (2002) · Vitamins and hormones · doi:10.1016/s0083-6729(02)65068-x · Cited by 40
Mechanisms of the anorexia of aging in the Brown Norway rat
Wolden‐Hanson, T. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.05.032 · Cited by 38
Understanding how discrete populations of hypothalamic neurons orchestrate complicated behavioral states
Graebner, A. K., Iyer, M., & Carter, M. E. (2015) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2015.00111 · Cited by 37
“Central injection of the AgRP peptide promotes feeding (Rossi et al., 1998) and chronic overexpression of AgRP causes obesity (Graham et al., 1997; Ollmann et al., 1997).”
Background
Feeding effects of melanocortin ligands—A historical perspective
Irani, B. G., & Haskell‐Luevano, C. (2005) · Peptides · doi:10.1016/j.peptides.2004.11.038 · Cited by 37
Differential effects of methamphetamine on expression of neuropeptide Y mRNA in hypothalamus and on serum leptin and ghrelin concentrations in ad libitum-fed and schedule-fed rats
Crowley, W. R., Ramoz, G., Keefe, K. A., Torto, R., Kalra, S. P., & Hanson, G. R. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2004.11.037 · Cited by 37
Novel hypophysiotropic AgRP2 neurons and pineal cells revealed by BAC transgenesis in zebrafish
Shainer, I., Hazak, A., Hawkins, T. A., Wilson, S. W., Cone, R. D., & Gothilf, Y. (2017) · Scientific Reports · doi:10.1038/srep44777 · Cited by 37
Feeding responses to a melanocortin agonist and antagonist in obesity induced by a palatable high-fat diet
Hansen, M. J., Schiöth, H. B., & Morris, M. J. (2005) · Brain Research · doi:10.1016/j.brainres.2005.01.063 · Cited by 36
Naturally occurring mutations in G protein-coupled receptors associated with obesity and type 2 diabetes mellitus
Liu, T., Ji, R.-L., & Tao, Y.-X. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.108044 · Cited by 34

Authors: 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., Smith, D. M., Yagaloff, K., Ghatei, M. A., & Bloom, S. R.
Affiliations: Hammersmith Hospital (GB)
ORCID: Abusnana, S.
Goldstone, A. P.
Stanley, S. A.
Smith, D. M.
Bloom, S. R.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 1998-10
Volume: 139
Issue: 10
Pages: 4428-4431
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/endo.139.10.6332
OpenAlex: W2171010063
Cited by: 576
References: 0
Citations by year: 2026: 2 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 11 · 2020: 7 · 2019: 16 · 2018: 8 · 2017: 13 · 2016: 16 · 2015: 15 · 2014: 16 · 2013: 22 · 2012: 29
FWCI: 11.74
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
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, C-terminal fragment, alpha-melanocyte-stimulating hormone, melanocortin 3 receptor, melanocortin-4 receptor, dietary intake, hyperphagia, SHU9119, obesity, hypothalamus, cAMP signaling, intracerebroventricular administration
MeSH terms: alpha-MSH, Animals, Dose-Response Relationship, Drug, Eating, Injections, Intraventricular, Male, Peptide Fragments, Proteins, Rats, Wistar, Receptors, Corticotropin, Intercellular Signaling Peptides and Proteins, Receptor, Melanocortin, Type 3, Rats, Agouti Signaling Protein, Agouti-Related Protein

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A C-Terminal Fragment of Agouti-Related Protein Increases Feeding and Antagonizes the Effect of Alpha-Melanocyte Stimulating Hormone in Vivo

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