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1

Oh, Youjin, Eun-Seon Yoo, Sang Hyeon Ju, et al. "GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice." PLOS Biology 21, no. 8 (2023): e3002252. http://dx.doi.org/10.1371/journal.pbio.3002252.

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It is well known that the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons increase appetite and decrease thermogenesis. Previous studies demonstrated that optogenetic and/or chemogenetic manipulations of NPY/AgRP neuronal activity alter food intake and/or energy expenditure (EE). However, little is known about intrinsic molecules regulating NPY/AgRP neuronal excitability to affect long-term metabolic function. Here, we found that the G protein-gated inwardly rectifying K+ (GIRK) channels are key to stabilize NPY/AgRP neurons and that NPY/AgRP neuron-selective deletion of the GIRK2 s
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van de Wall, Esther, Rebecca Leshan, Allison W. Xu, et al. "Collective and Individual Functions of Leptin Receptor Modulated Neurons Controlling Metabolism and Ingestion." Endocrinology 149, no. 4 (2007): 1773–85. http://dx.doi.org/10.1210/en.2007-1132.

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Two known types of leptin-responsive neurons reside within the arcuate nucleus: the agouti gene-related peptide (AgRP)/neuropeptide Y (NPY) neuron and the proopiomelanocortin (POMC) neuron. By deleting the leptin receptor gene (Lepr) specifically in AgRP/NPY and/or POMC neurons of mice, we examined the several and combined contributions of these neurons to leptin action. Body weight and adiposity were increased by Lepr deletion from AgRP and POMC neurons individually, and simultaneous deletion in both neurons (A+P LEPR-KO mice) further increased these measures. Young (periweaning) A+P LEPR-KO
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Coutinho, Eulalia A., Melanie Prescott, Sabine Hessler, Christopher J. Marshall, Allan E. Herbison, and Rebecca E. Campbell. "Activation of a Classic Hunger Circuit Slows Luteinizing Hormone Pulsatility." Neuroendocrinology 110, no. 7-8 (2019): 671–87. http://dx.doi.org/10.1159/000504225.

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Introduction: The central regulation of fertility is carefully coordinated with energy homeostasis, and infertility is frequently the outcome of energy imbalance. Neurons in the hypothalamus expressing neuropeptide Y and agouti-related peptide (NPY/AgRP neurons) are strongly implicated in linking metabolic cues with fertility regulation. Objective: We aimed here to determine the impact of selectively activating NPY/AgRP neurons, critical regulators of metabolism, on the activity of luteinizing hormone (LH) pulse generation. Methods: We employed a suite of in vivo optogenetic and chemogenetic a
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Jones, Edward S., Nicolas Nunn, Adam P. Chambers, Søren Østergaard, Birgitte S. Wulff, and Simon M. Luckman. "Modified Peptide YY Molecule Attenuates the Activity of NPY/AgRP Neurons and Reduces Food Intake in Male Mice." Endocrinology 160, no. 11 (2019): 2737–47. http://dx.doi.org/10.1210/en.2019-00100.

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Abstract To study the effects of an analog of the gut-produced hormone peptide YY (PYY3-36), which has increased selectivity for the Y2 receptor; specifically, to record its effects on food intake and on hypothalamic neuropeptide Y/agouti-related peptide (NPY/AgRP) neuron activity. NNC0165-1273, a modified form of the peptide hormone PYY3-36 with potent selectivity at Y2 receptor (>5000-fold over Y1, 1250-fold over Y4, and 650-fold over Y5 receptor), was tested in vivo and in vitro in mouse models. NNC0165-1273 has fivefold lower relative affinity for Y2 compared with PYY3-36, but >250-,
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Morton, GJ, and MW Schwartz. "The NPY/AgRP neuron and energy homeostasis." International Journal of Obesity 25, S5 (2001): S56—S62. http://dx.doi.org/10.1038/sj.ijo.0801915.

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Landry, Taylor, Daniel Shookster, Alec Chaves, Katrina Free, Tony Nguyen, and Hu Huang. "Exercise increases NPY/AgRP and TH neuron activity in the hypothalamus of female mice." Journal of Endocrinology 252, no. 3 (2022): 167–77. http://dx.doi.org/10.1530/joe-21-0250.

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Recent evidence identifies a potent role for aerobic exercise to modulate the activity of hypothalamic neurons related to appetite; however, these studies have been primarily performed in male rodents. Since females have markedly different neuronal mechanisms regulating food intake, the current study aimed to determine the effects of acute treadmill exercise on hypothalamic neuron populations involved in regulating appetite in female mice. Mature, untrained female mice were exposed to acute sedentary, low- (10 m/min), moderate- (14 m/min), and high (18 m/min)-intensity treadmill exercise in a
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7

Smith, A. W., M. A. Bosch, E. J. Wagner, O. K. Rønnekleiv та M. J. Kelly. "The membrane estrogen receptor ligand STX rapidly enhances GABAergic signaling in NPY/AgRP neurons: role in mediating the anorexigenic effects of 17β-estradiol". American Journal of Physiology-Endocrinology and Metabolism 305, № 5 (2013): E632—E640. http://dx.doi.org/10.1152/ajpendo.00281.2013.

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Besides its quintessential role in reproduction, 17β-estradiol (E2) is a potent anorexigenic hormone. E2 and the selective Gq-coupled membrane estrogen receptor (Gq-mER) ligand STX rapidly increase membrane excitability in proopiomelanocortin (POMC) neurons by desensitizing the coupling of GABAB receptors to G protein-coupled inwardly rectifying K+ channels (GIRKs), which upon activation elicit a hyperpolarizing outward current. However, it is unknown whether E2 and STX can modulate GABAB signaling in neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons. We used single-cell RT-PCR and wh
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Teaney, Nicole A., and Nicole E. Cyr. "Sirtuin 1 Regulates Synapsin 1 in POMC-Producing N43-5 Neurons via FOXO1." Journal of the Endocrine Society 5, Supplement_1 (2021): A56—A57. http://dx.doi.org/10.1210/jendso/bvab048.114.

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Abstract The nutrient-sensor protein Sirtuin 1 (Sirt1; silent mating type information regulation 2 homolog 1) has been shown to have significant and opposing effects on insulin resistance, leptin resistance, and body weight in the periphery and the brain. In the hypothalamic arcuate nucleus (ARC) of the brain, Sirt1 increases in the obese state and acts to promote weight gain as well as insulin and leptin resistance by increasing the orexigenic neuropeptides Agouti-related protein (AgRP) and neuropeptide Y (NPY), and in a distinct set of ARC neurons, by decreasing POMC and thus its anorexigeni
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9

Johnson, Miranda D., Sebastien G. Bouret, Ambrose A. Dunn-Meynell, Christina N. Boyle, Thomas A. Lutz, and Barry E. Levin. "Early postnatal amylin treatment enhances hypothalamic leptin signaling and neural development in the selectively bred diet-induced obese rat." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 311, no. 6 (2016): R1032—R1044. http://dx.doi.org/10.1152/ajpregu.00326.2016.

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Selectively bred diet-induced obese (DIO) rats become obese on a high-fat diet and are leptin resistant before becoming obese. Compared with diet-resistant (DR) neonates, DIO neonates have impaired leptin-dependent arcuate (ARC) neuropeptide Y/agouti-related peptide (NPY/AgRP) and α-melanocyte-stimulating hormone (α-MSH; from proopiomelanocortin (POMC) neurons) axon outgrowth to the paraventricular nucleus (PVN). Using phosphorylation of STAT3 (pSTAT3) as a surrogate, we show that reduced DIO ARC leptin signaling develops by postnatal day 7 (P7) and is reduced within POMC but not NPY/AgRP neur
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Krashes, Michael J., Bhavik P. Shah, Shuichi Koda, and Bradford B. Lowell. "Rapid versus Delayed Stimulation of Feeding by the Endogenously Released AgRP Neuron Mediators GABA, NPY, and AgRP." Cell Metabolism 18, no. 4 (2013): 588–95. http://dx.doi.org/10.1016/j.cmet.2013.09.009.

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Landry, Taylor, Brenton Thomas Laing, Peixin Li та ін. "Central α-Klotho Suppresses NPY/AgRP Neuron Activity and Regulates Metabolism in Mice". Diabetes 69, № 7 (2020): 1368–81. http://dx.doi.org/10.2337/db19-0941.

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Marcelin, Geneviève, Young-Hwan Jo, Xiaosong Li, et al. "Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism." Molecular Metabolism 3, no. 1 (2014): 19–28. http://dx.doi.org/10.1016/j.molmet.2013.10.002.

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13

Bunner, Wyatt P., Brenton T. Laing, and Hu Huang. "The Effects Of Acute Exercise On Npy/AgRP And POMC Neuron Activity In The Mouse Hypothalamus." Medicine & Science in Sports & Exercise 50, no. 5S (2018): 840. http://dx.doi.org/10.1249/01.mss.0000538766.62883.64.

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Li, Peixin, Zhijian Rao, Brenton Thomas Laing, et al. "Vertical sleeve gastrectomy improves liver and hypothalamic functions in obese mice." Journal of Endocrinology 241, no. 2 (2019): 135–47. http://dx.doi.org/10.1530/joe-18-0658.

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Vertical sleeve gastrectomy (VSG) is an effective surgery to treat obesity and diabetes. However, the direct effect of VSG on metabolic functions is not fully understood. We aimed to investigate if alterations in hypothalamic neurons were linked with perturbations in liver metabolism after VSG in an energy intake-controlled obese mouse model. C57BL/6 and hrNPY-GFP reporter mice received HFD for 12 weeks and were then divided into three groups: Sham (ad lib), Sham (pair-fed) with VSG and VSG. Food intake was measured daily, and blood glucose levels were measured before and after the study. Ener
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15

Feng, Bing, Frank Greenway, Jerney Harms, et al. "OR23-3 Hunger Hormone Asprosin Activates Orexigenic Neurons via SK Currents." Journal of the Endocrine Society 6, Supplement_1 (2022): A19. http://dx.doi.org/10.1210/jendso/bvac150.039.

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Abstract Neurons that co-express the orexigenic agouti-related protein (AgRP) and neuropeptide Y (NPY) are indispensable for normal feeding behavior. Firing activities of AgRP/NPY neurons dynamically fluctuate with energy status and coordinate appropriate feeding behavior to meet nutritional demands. We previously demonstrated that asprosin, a recently discovered fasting-induced glucogenic and orexigenic hormone, crosses the blood-brain barrier and directly activates the orexigenic AgRP/NPY neurons via a cyclic cAMP-dependent pathway. However, intrinsic mechanisms on how asprosin regulates AgR
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16

Goldstone, Anthony P., Unga A. Unmehopa, Stephen R. Bloom, and Dick F. Swaab. "Hypothalamic NPY and Agouti-Related Protein Are Increased in Human Illness But Not in Prader-Willi Syndrome and Other Obese Subjects." Journal of Clinical Endocrinology & Metabolism 87, no. 2 (2002): 927–37. http://dx.doi.org/10.1210/jcem.87.2.8230.

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Animal studies have demonstrated the importance of orexigenic NPY and agouti-related protein (AGRP) hypothalamic neurons, which are inhibited by the adipocyte hormone leptin, in the regulation of body weight and neuroendocrine secretion. We have examined NPY and AGRP neurons in postmortem human hypothalami from controls, Prader-Willi syndrome and other obese subjects, using quantitative immunocytochemistry (ICC) and in situ hybridization, to identify causes of leptin resistance in human obesity. Using combined ICC and in situ hybridization, AGRP, but not POMC, was colocalized with NPY in infun
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Bugarith, Kishor, Thu T. Dinh, Ai-Jun Li, Robert C. Speth, and Sue Ritter. "Basomedial Hypothalamic Injections of Neuropeptide Y Conjugated to Saporin Selectively Disrupt Hypothalamic Controls of Food Intake." Endocrinology 146, no. 3 (2005): 1179–91. http://dx.doi.org/10.1210/en.2004-1166.

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Neuropeptide Y (NPY) conjugated to saporin (NPY-SAP), a ribosomal inactivating toxin, is a newly developed compound designed to selectively target and lesion NPY receptor-expressing cells. We injected NPY-SAP into the basomedial hypothalamus (BMH), just dorsal to the arcuate nucleus (ARC), to investigate its neurotoxicity and to determine whether ARC NPY neurons are required for glucoprivic feeding. We found that NPY-SAP profoundly reduced NPY Y1 receptor and αMSH immunoreactivity, as well as NPY, Agouti gene-related protein (AGRP), and cocaine and amphetamine-related transcript mRNA expressio
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Fraley, G. S., and S. Ritter. "Immunolesion of Norepinephrine and Epinephrine Afferents to Medial Hypothalamus Alters Basal and 2-Deoxy-d-Glucose-Induced Neuropeptide Y and Agouti Gene-Related Protein Messenger Ribonucleic Acid Expression in the Arcuate Nucleus." Endocrinology 144, no. 1 (2003): 75–83. http://dx.doi.org/10.1210/en.2002-220659.

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Abstract Neuropeptide Y (NPY) and agouti gene-related protein (AGRP) are orexigenic peptides of special importance for control of food intake. In situ hybridization studies have shown that NPY and AGRP mRNAs are increased in the arcuate nucleus of the hypothalamus (ARC) by glucoprivation. Other work has shown that glucoprivation stimulates food intake by activation of hindbrain glucoreceptor cells and requires the participation of rostrally projecting norepinephrine (NE) or epinephrine (E) neurons. Here we determine the role of hindbrain catecholamine afferents in glucoprivation-induced increa
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Phillips, Colin T., and Richard D. Palmiter. "Role of Agouti-Related Protein-Expressing Neurons in Lactation." Endocrinology 149, no. 2 (2007): 544–50. http://dx.doi.org/10.1210/en.2007-1153.

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Hypothalamic neurons that express agouti-related protein (AgRP) and neuropeptide Y (NPY) are thought to be important for regulation of feeding, especially under conditions of negative energy balance. The expression of NPY and AgRP increases during lactation and may promote the hyperphagia that ensues. We explored the role of AgRP neurons in reproduction and lactation, using a mouse model in which AgRP-expressing neurons were selectively ablated by the action of diphtheria toxin. We show that ablation of AgRP neurons in neonatal mice does not interfere with pregnancy, parturition, or lactation,
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Olofsson, Louise E., Andrew A. Pierce, and Allison W. Xu. "Functional requirement of AgRP and NPY neurons in ovarian cycle-dependent regulation of food intake." Proceedings of the National Academy of Sciences 106, no. 37 (2009): 15932–37. http://dx.doi.org/10.1073/pnas.0904747106.

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In female mammals including rodents and humans, feeding decreases during the periovulatory period of the ovarian cycle, which coincides with a surge in circulating estrogen levels. Ovariectomy increases food intake, which can be normalized by estrogen treatment at a dose and frequency mimicking those during the estrous cycle. Furthermore, administration of estrogen to rodents potently inhibits food intake. Despite these well-known effects of estrogen, neuronal subtypes that mediate estrogen's anorexigenic effects have not been identified. In this study, we show that changes in hypothalamic exp
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Gong, Lijie, Fayi Yao, Kristin Hockman, et al. "Signal Transducer and Activator of Transcription-3 Is Required in Hypothalamic Agouti-Related Protein/Neuropeptide Y Neurons for Normal Energy Homeostasis." Endocrinology 149, no. 7 (2008): 3346–54. http://dx.doi.org/10.1210/en.2007-0945.

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Signal transducer and activator of transcription (Stat)-3 signals mediate many of the metabolic effects of the fat cell-derived hormone, leptin. In mice, brain-specific depletion of either the long form of the leptin receptor (Lepr) or Stat3 results in comparable obese phenotypes as does replacement of Lepr with an altered leptin receptor locus that codes for a Lepr unable to interact with Stat3. Among the multiple brain regions containing leptin-sensitive Stat3 sites, cells expressing feeding-related neuropeptides in the arcuate nucleus of the hypothalamus have received much of the focus. To
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Kas, Martien J. H., Adrie W. Bruijnzeel, Jurgen R. Haanstra, Victor M. Wiegant, and Roger A. H. Adan. "Differential regulation of agouti-related protein and neuropeptide Y in hypothalamic neurons following a stressful event." Journal of Molecular Endocrinology 35, no. 1 (2005): 159–64. http://dx.doi.org/10.1677/jme.1.01819.

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Stress affects eating behaviour in rodents and humans, suggesting that the regulation of energy balance and the stress response are coupled physiological processes. Neuropeptide Y (NPY) and agouti-related protein (AgRP) are potent food-stimulating neuropeptides that are highly co-localised in arcuate nucleus neurons of the hypothalamus. Recent studies have shown that NPY and AgRP mRNA levels in these neurons respond similarly to fasting and leptin, indicating functional redundancy of the neuropeptide systems in these orexigenic neurons. However, we have found that NPY and AgRP mRNA expression
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Qian, Su, Howard Chen, Drew Weingarth, et al. "Neither Agouti-Related Protein nor Neuropeptide Y Is Critically Required for the Regulation of Energy Homeostasis in Mice." Molecular and Cellular Biology 22, no. 14 (2002): 5027–35. http://dx.doi.org/10.1128/mcb.22.14.5027-5035.2002.

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ABSTRACT Agouti-related protein (AgRP), a neuropeptide abundantly expressed in the arcuate nucleus of the hypothalamus, potently stimulates feeding and body weight gain in rodents. AgRP is believed to exert its effects through the blockade of signaling by α-melanocyte-stimulating hormone at central nervous system (CNS) melanocortin-3 receptor (Mc3r) and Mc4r. We generated AgRP-deficient (Agrp−/− ) mice to examine the physiological role of AgRP. Agrp−/− mice are viable and exhibit normal locomotor activity, growth rates, body composition, and food intake. Additionally, Agrp−/− mice display norm
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Zhang, Juan, Yunting Zhou, Cheng Chen, et al. "ERK1/2 mediates glucose-regulated POMC gene expression in hypothalamic neurons." Journal of Molecular Endocrinology 54, no. 2 (2015): 125–35. http://dx.doi.org/10.1530/jme-14-0330.

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Hypothalamic glucose-sensing neurons regulate the expression of genes encoding feeding-related neuropetides POMC, AgRP, and NPY – the key components governing metabolic homeostasis. AMP-activated protein kinase (AMPK) is postulated to be the molecular mediator relaying glucose signals to regulate the expression of these neuropeptides. Whether other signaling mediator(s) plays a role is not clear. In this study, we investigated the role of ERK1/2 using primary hypothalamic neurons as the model system. The primary neurons were differentiated from hypothalamic progenitor cells. The differentiated
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Chen, Peilin, Chien Li, Carrie Haskell-Luevano, Roger D. Cone, and M. Susan Smith. "Altered Expression of Agouti-Related Protein and Its Colocalization with Neuropeptide Y in the Arcuate Nucleus of the Hypothalamus during Lactation*." Endocrinology 140, no. 6 (1999): 2645–50. http://dx.doi.org/10.1210/endo.140.6.6829.

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Abstract During lactation, the levels of neuropeptide Y (NPY), which plays an important role in mediating food intake, are significantly elevated in a number of hypothalamic areas, including the arcuate nucleus (ARH). To identify additional hypothalamic systems that might be important in mediating the increase in food intake and alterations in energy homeostasis during lactation, the present studies examined the expression of agouti-related protein (AGRP), a recently described homologue of the skin agouti protein. AGRP is found in the hypothalamus and has been suggested to play an important ro
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Turi, Gergely F., Zsolt Liposits, Suzanne M. Moenter, Csaba Fekete, and Erik Hrabovszky. "Origin of Neuropeptide Y-Containing Afferents to Gonadotropin-Releasing Hormone Neurons in Male Mice." Endocrinology 144, no. 11 (2003): 4967–74. http://dx.doi.org/10.1210/en.2003-0470.

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Abstract The origin of neuropeptide Y (NPY) afferents to GnRH neurons was investigated in male mice. Neonatal lesioning of the hypothalamic arcuate nuclei (ARC) with monosodium glutamate markedly reduced the number of NPY fibers in the preoptic area as well as the frequency of their contacts with perikarya and proximal dendrites of GnRH neurons. Dual-label immunofluorescence studies to determine the precise contribution of the ARC to the innervation of GnRH neurons by NPY axons were carried out on transgenic mice in which enhanced green fluorescent protein was expressed under the control of th
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Kurita, Hideharu, Kai Y. Xu, Yuko Maejima, et al. "Arcuate Na+,K+-ATPase senses systemic energy states and regulates feeding behavior through glucose-inhibited neurons." American Journal of Physiology-Endocrinology and Metabolism 309, no. 4 (2015): E320—E333. http://dx.doi.org/10.1152/ajpendo.00446.2014.

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Feeding is regulated by perception in the hypothalamus, particularly the first-order arcuate nucleus (ARC) neurons, of the body's energy state. However, the cellular device for converting energy states to the activity of critical neurons in ARC is less defined. We here show that Na+,K+-ATPase (NKA) in ARC senses energy states to regulate feeding. Fasting-induced systemic ghrelin rise and glucose lowering reduced ATP-hydrolyzing activity of NKA and its substrate ATP level, respectively, preferentially in ARC. Lowering glucose concentration (LG), which mimics fasting, decreased intracellular NAD
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Briggs, Dana I., Pablo J. Enriori, Moyra B. Lemus, Michael A. Cowley, and Zane B. Andrews. "Diet-Induced Obesity Causes Ghrelin Resistance in Arcuate NPY/AgRP Neurons." Endocrinology 151, no. 10 (2010): 4745–55. http://dx.doi.org/10.1210/en.2010-0556.

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Circulating ghrelin is decreased in obesity, and peripheral ghrelin does not induce food intake in obese mice. We investigated whether ghrelin resistance was a centrally mediated phenomenon involving dysregulated neuropeptide Y (NPY) and agouti-related peptide (AgRP) circuits. We show that diet-induced obesity (DIO) (12 wk) suppresses the neuroendocrine ghrelin system by decreasing acylated and total plasma ghrelin, decreasing ghrelin and Goat mRNA in the stomach, and decreasing expression of hypothalamic GHSR. Peripheral (ip) or central (intracerebroventricular) ghrelin injection was able to
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Goto, Motomitsu, Hiroshi Arima, Minemori Watanabe, et al. "Ghrelin Increases Neuropeptide Y and Agouti-Related Peptide Gene Expression in the Arcuate Nucleus in Rat Hypothalamic Organotypic Cultures." Endocrinology 147, no. 11 (2006): 5102–9. http://dx.doi.org/10.1210/en.2006-0104.

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Ghrelin, which was identified from the rat stomach, is a potent stimulant for food intake. Several lines of evidence suggest that the orexigenic action of ghrelin is mediated via the neuropeptide Y (NPY) neurons in the arcuate nucleus, although the detailed mechanisms by which ghrelin stimulates NPY neurons are not clear. In this study, we examined the gene regulation of NPY and agouti-related peptide (AGRP), another orexigenic peptide synthesized in the NPY neurons, in the arcuate nucleus by ghrelin in hypothalamic organotypic cultures. Incubation of the hypothalamic explants with ghrelin sig
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Zheng, Huiyuan, Michele M. Corkern, Scott M. Crousillac, Laurel M. Patterson, Curtis B. Phifer, and Hans-Rudolf Berthoud. "Neurochemical phenotype of hypothalamic neurons showing Fos expression 23 h after intracranial AgRP." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 282, no. 6 (2002): R1773—R1781. http://dx.doi.org/10.1152/ajpregu.00019.2002.

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Agouti-related protein (AgRP) is coexpressed with neuropeptide Y (NPY) in a population of neurons in the arcuate nucleus (ARC) of the hypothalamus and stimulates food intake for up to 7 days if injected intracerebroventricularly. The prolonged food intake stimulation does not seem to depend on continued competition at the melanocortin-4 receptor (MC4R), because the relatively specific MC4R agonist MTII regains its ability to suppress food intake 24 h after AgRP injection. Intracerebroventricular AgRP also stimulates c-Fos expression 24 h after injection in several brain areas, so the neurons e
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Qiu, Jian, Martha A. Bosch, Chungang Zhang, Oline K. Rønnekleiv, and Martin J. Kelly. "Estradiol Protects Neuropeptide Y/Agouti-Related Peptide Neurons against Insulin Resistance in Females." Neuroendocrinology 110, no. 1-2 (2019): 105–18. http://dx.doi.org/10.1159/000501560.

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When it comes to obesity, men exhibit a higher incidence of metabolic syndrome than women in early adult life, but this sex advantage wanes in postmenopausal women. A key diagnostic of the metabolic syndrome is insulin resistance in both peripheral tissues and brain, especially in the hypothalamus. Since the anorexigenic hormone 17β-estradiol (E2) regulates food intake in part by inhibiting the excitability of the hypothalamic neuropeptide Y/agouti-related peptide (NPY/AgRP) neurons, we hypothesized that E2 would protect against insulin resistance in NPY/AgRP neurons with diet-induced obesity
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Morrison, Christopher D., Gregory J. Morton, Kevin D. Niswender, Richard W. Gelling, and Michael W. Schwartz. "Leptin inhibits hypothalamic Npy and Agrp gene expression via a mechanism that requires phosphatidylinositol 3-OH-kinase signaling." American Journal of Physiology-Endocrinology and Metabolism 289, no. 6 (2005): E1051—E1057. http://dx.doi.org/10.1152/ajpendo.00094.2005.

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Phosphatidylinositol 3-OH-kinase (PI3K) and STAT3 are signal transduction molecules activated by leptin in brain areas controlling food intake. To investigate their role in leptin-mediated inhibition of hypothalamic neuropeptide Y ( Npy) and agouti-related peptide ( Agrp) gene expression, male Sprague-Dawley rats ( n = 5/group) were either fed ad libitum or subjected to a 52-h fast. At 12-h intervals, the PI3K inhibitor LY-294002 (LY, 1 nmol) or vehicle was injected intracerebroventricularly (ICV) as a pretreatment, followed 1 h later by leptin (3 μg icv) or vehicle. Fasting increased hypothal
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33

Gyengesi, Erika, Zhong-Wu Liu, Giuseppe D'Agostino, et al. "Corticosterone Regulates Synaptic Input Organization of POMC and NPY/AgRP Neurons in Adult Mice." Endocrinology 151, no. 11 (2010): 5395–402. http://dx.doi.org/10.1210/en.2010-0681.

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Changes in circulating hormones, such as leptin and ghrelin, induce alterations in synaptic input organization and electrophysiological properties of neurons of the arcuate nucleus of the hypothalamus. To assess whether changes in circulating glucocorticoids also alter synaptic arrangement and membrane potential properties, we studied the effect of adrenalectomy (ADX) and corticosterone replacement in mice on the proopiomelanocortin (POMC) and neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons of the hypothalamic arcuate nucleus. ADX reduced the number of symmetric, putative inhibitory
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34

Teubner, Brett J. W., Erin Keen-Rhinehart, and Timothy J. Bartness. "Third ventricular coinjection of subthreshold doses of NPY and AgRP stimulate food hoarding and intake and neural activation." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 302, no. 1 (2012): R37—R48. http://dx.doi.org/10.1152/ajpregu.00475.2011.

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We previously demonstrated that 3rd ventricular (3V) neuropeptide Y (NPY) or agouti-related protein (AgRP) injection potently stimulates food foraging/hoarding/intake in Siberian hamsters. Because NPY and AgRP are highly colocalized in arcuate nucleus neurons in this and other species, we tested whether subthreshold doses of NPY and AgRP coinjected into the 3V stimulates food foraging, hoarding, and intake, and/or neural activation [c-Fos immunoreactivity (c-Fos-ir)] in hamsters housed in a foraging/hoarding apparatus. In the behavioral experiment, each hamster received four 3V treatments by u
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35

Sánchez, Edith, Praful S. Singru, Runa Acharya, et al. "Differential Effects of Refeeding on Melanocortin-Responsive Neurons in the Hypothalamic Paraventricular Nucleus." Endocrinology 149, no. 9 (2008): 4329–35. http://dx.doi.org/10.1210/en.2008-0411.

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To explore the effect of refeeding on recovery of TRH gene expression in the hypothalamic paraventricular nucleus (PVN) and its correlation with the feeding-related neuropeptides in the arcuate nucleus (ARC), c-fos immunoreactivity (IR) in the PVN and ARC 2 h after refeeding and hypothalamic TRH, neuropeptide Y (NPY) and agouti-related protein (AGRP) mRNA levels 4, 12, and 24 h after refeeding were studied in Sprague-Dawley rats subjected to prolonged fasting. Despite rapid reactivation of proopiomelanocortin neurons by refeeding as demonstrated by c-fos IR in ARC α-MSH-IR neurons and ventral
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36

Sheffer-Babila, Sharone, Yan Sun, Davelene D. Israel, Shun-Mei Liu, Genevieve Neal-Perry, and Streamson C. Chua. "Agouti-related peptide plays a critical role in leptin's effects on female puberty and reproduction." American Journal of Physiology-Endocrinology and Metabolism 305, no. 12 (2013): E1512—E1520. http://dx.doi.org/10.1152/ajpendo.00241.2013.

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Deficient leptin signaling causes infertility via reduced activity of GnRH neurons, causing a hypogonadal state in both rodents and humans. Because GnRH neurons do not express leptin receptors, leptin's effect on GnRH neurons must be indirect. Neurons within the hypothalamic arcuate nucleus that coexpress AGRP and NPY are considered to be important intermediate neurons involved in leptin regulation of GnRH neurons. Previously, we reported that the absence of AGRP and haploinsufficiency of MC4R in leptin receptor mutant ( Lepr db/db ) females result in restoration of fertility and lactation des
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Bi, Sheng, Benjamin M. Robinson, and Timothy H. Moran. "Acute food deprivation and chronic food restriction differentially affect hypothalamic NPY mRNA expression." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 285, no. 5 (2003): R1030—R1036. http://dx.doi.org/10.1152/ajpregu.00734.2002.

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Although acute food deprivation and chronic food restriction both result in body weight loss, they produce different metabolic states. To evaluate how these two treatments affect hypothalamic peptide systems involved in energy homeostasis, we compared patterns of hypothalamic neuropeptide Y (NPY), agouti-related protein (AgRP), proopiomelanocotin (POMC), and leptin receptor gene expression in acutely food-deprived and chronically food-restricted rats. Both acute food deprivation and chronic food restriction reduced body weight and circulating leptin levels and resulted in increased arcuate NPY
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Rønnekleiv, Oline K., Jian Qiu, and Martin J. Kelly. "Arcuate Kisspeptin Neurons Coordinate Reproductive Activities with Metabolism." Seminars in Reproductive Medicine 37, no. 03 (2019): 131–40. http://dx.doi.org/10.1055/s-0039-3400251.

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AbstractHypothalamic control of fertility is the quintessential homeostatic function. However, fertility is metabolically demanding; so, there must be coordination between energy states and reproductive functions. Because gonadotropin-releasing hormone (GnRH) neurons are devoid of many of the critical metabolic hormone receptors for sensing nutrient levels, it has long been recognized that the sensing of energy stores had to be done by neurons presynaptic to GnRH neurons. Some of the obvious players have been the anorexigenic proopiomelanocortin (POMC) and orexigenic neuropeptide Y (NPY)/agout
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Vulliémoz, Nicolas R., Ennian Xiao, Linna Xia-Zhang, Sharon L. Wardlaw, and Michel Ferin. "Central Infusion of Agouti-Related Peptide Suppresses Pulsatile Luteinizing Hormone Release in the Ovariectomized Rhesus Monkey." Endocrinology 146, no. 2 (2005): 784–89. http://dx.doi.org/10.1210/en.2004-1093.

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Abstract Agouti-related peptide (AGRP), an endogenous melanocortin receptor antagonist, is a powerful orexigenic peptide when infused centrally. AGRP and neuropeptide Y (NPY), another orexigenic peptide, are colocated within the same neurons in the arcuate nucleus. Both NPY and AGRP mRNA expression increases during food restriction, a condition that is known to suppress the GnRH pulse generator and reproductive function. Although NPY has been shown previously to suppress LH secretion in the ovariectomized monkey, data on AGRP are lacking. In this study, we examined the effect of AGRP infusion
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40

Tang-Christensen, Mads, Niels Vrang, Sylvia Ortmann, Martin Bidlingmaier, Tamas L. Horvath, and Matthias Tschöp. "Central Administration of Ghrelin and Agouti-Related Protein (83–132) Increases Food Intake and Decreases Spontaneous Locomotor Activity in Rats." Endocrinology 145, no. 10 (2004): 4645–52. http://dx.doi.org/10.1210/en.2004-0529.

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Abstract Ghrelin was recently identified as an endogenous ligand of the GH secretagogue receptor. The novel peptide hormone is produced by gastric A-like cells, and circulating levels rise before feeding, suggestive of ghrelin as an endogenous hunger factor. ghrelin stimulates food intake and promotes adiposity after peripheral or central administration, likely by activating hypothalamic neurons expressing the orexigenic neuropeptides neuropeptide Y (NPY) and agouti-related protein (AGRP). To examine whether ghrelin-induced feeding resembles NPY and AGRP [AGRP fragment (83–132)] induced orexia
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41

Sominsky, Luba, Ilvana Ziko, Thai-Xinh Nguyen, Julie Quach, and Sarah J. Spencer. "Hypothalamic effects of neonatal diet: reversible and only partially leptin dependent." Journal of Endocrinology 234, no. 1 (2017): 41–56. http://dx.doi.org/10.1530/joe-16-0631.

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Early life diet influences metabolic programming, increasing the risk for long-lasting metabolic ill health. Neonatally overfed rats have an early increase in leptin that is maintained long term and is associated with a corresponding elevation in body weight. However, the immediate and long-term effects of neonatal overfeeding on hypothalamic anorexigenic pro-opiomelanocortin (POMC) and orexigenic agouti-related peptide (AgRP)/neuropeptide Y (NPY) circuitry, and if these are directly mediated by leptin, have not yet been examined. Here, we examined the effects of neonatal overfeeding on leptin
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42

Bewick, Gavin A., Waljit S. Dhillo, Sarah J. Darch, et al. "Hypothalamic Cocaine- and Amphetamine-Regulated Transcript (CART) and Agouti-Related Protein (AgRP) Neurons Coexpress the NOP1 Receptor and Nociceptin Alters CART and AgRP Release." Endocrinology 146, no. 8 (2005): 3526–34. http://dx.doi.org/10.1210/en.2004-1659.

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Abstract Nociceptin or orphanin FQ (N/OFQ) and its receptor NOP1 are expressed in hypothalamic nuclei involved in energy homeostasis. N/OFQ administered by intracerebroventricular or arcuate nucleus (ARC) injection increases food intake in satiated rats. The mechanisms by which N/OFQ increases food intake are unknown. We hypothesized that N/OFQ may regulate hypothalamic neurons containing peptides involved in the control of food intake such as cocaine- and amphetamine-regulated transcript (CART), αMSH, neuropeptide Y (NPY), and agouti-related protein (AgRP). We investigated the ability of N/OF
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43

Sayers, Sarah, and Ed Wagner. "On the Pleiotropic Actions of Glucagon-like Peptide-1 in Its Regulation of Homeostatic and Hedonic Feeding." International Journal of Molecular Sciences 26, no. 8 (2025): 3897. https://doi.org/10.3390/ijms26083897.

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We examined the neuroanatomical substrates and signaling mechanisms underlying the suppressive effect of GLP1 on homeostatic and hedonic feeding. Electrophysiological and behavioral studies were conducted in agouti-related peptide (AgRP)-cre and tyrosine hydroxylase (TH)-cre mice, and AgRP-cre/pituitary adenylyl cyclase-activating polypeptide (PACAP) type I receptor (PAC1R)fl/fl animals. GLP1 (30 pmol) delivered directly into the arcuate nucleus (ARC) decreased homeostatic feeding and diminished the rate of consumption. This anorexigenic effect was associated with an inhibitory outward current
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Desai, Mina, Monica G. Ferrini, Guang Han, Kavita Narwani, and Michael G. Ross. "Maternal High Fat Diet Programs Male Mice Offspring Hyperphagia and Obesity: Mechanism of Increased Appetite Neurons via Altered Neurogenic Factors and Nutrient Sensor AMPK." Nutrients 12, no. 11 (2020): 3326. http://dx.doi.org/10.3390/nu12113326.

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Maternal high-fat (HF) is associated with offspring hyperphagia and obesity. We hypothesized that maternal HF alters fetal neuroprogenitor cell (NPC) and hypothalamic arcuate nucleus (ARC) development with preferential differentiation of neurons towards orexigenic (NPY/AgRP) versus anorexigenic (POMC) neurons, leading to offspring hyperphagia and obesity. Furthermore, these changes may involve hypothalamic bHLH neuroregulatory factors (Hes1, Mash1, Ngn3) and energy sensor AMPK. Female mice were fed either a control or a high fat (HF) diet prior to mating, and during pregnancy and lactation. HF
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Mercer, Julian G., Kim M. Moar, Alexander W. Ross, Nigel Hoggard, and Peter J. Morgan. "Photoperiod regulates arcuate nucleus POMC, AGRP, and leptin receptor mRNA in Siberian hamster hypothalamus." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 278, no. 1 (2000): R271—R281. http://dx.doi.org/10.1152/ajpregu.2000.278.1.r271.

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Siberian hamsters decreased body weight by 30% during 18 wk in short day (SD) vs. long day (LD) controls. Subsequent imposed food deprivation (FD; 24 h) caused a further 10% decrease. In the hypothalamic arcuate nucleus (ARC), SDs reduced proopiomelanocortin (POMC) gene expression and agouti-related protein (AGRP) mRNA was elevated, changes that summate to reduced catabolic drive through the melanocortin receptors. There was no effect of photoperiod on neuropeptide Y (NPY), melanin concentrating hormone, orexin, or corticotropin-releasing factor mRNAs. Superimposed FD increased AGRP gene expre
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Gil-Campos, Mercedes, Concepción María Aguilera, Ramón Cañete, and Angel Gil. "Ghrelin: a hormone regulating food intake and energy homeostasis." British Journal of Nutrition 96, no. 2 (2006): 201–26. http://dx.doi.org/10.1079/bjn20061787.

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Regulation of energy homeostasis requires precise coordination between peripheral nutrient-sensing molecules and central regulatory networks. Ghrelin is a twenty-eight-amino acid orexigenic peptide acylated at the serine 3 position mainly with an n-octanoic acid, which is produced mainly in the stomach. It is the endogenous ligand of the growth hormone secretagogue (GHS) receptors. Since plasma ghrelin levels are strictly dependent on recent food intake, this hormone plays an essential role in appetite and meal initiation. In addition, ghrelin is involved in the regulation of energy homeostasi
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Rafiei, Neda, Caitlin S. Mitchell, Caitlin R. Tedesco, et al. "Chemogenetic activation ofarcuate nucleus NPY and NPY/AgRP neurons increases feeding behaviour in mice." Neuropeptides 107 (October 2024): 102454. http://dx.doi.org/10.1016/j.npep.2024.102454.

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Fekete, Csaba, Praful S. Singru, Edith Sanchez, et al. "Differential Effects of Central Leptin, Insulin, or Glucose Administration during Fasting on the Hypothalamic-Pituitary-Thyroid Axis and Feeding-Related Neurons in the Arcuate Nucleus." Endocrinology 147, no. 1 (2006): 520–29. http://dx.doi.org/10.1210/en.2005-0956.

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The reductions in circulating levels of leptin, insulin, and glucose with fasting serve as important homeostasis signals to neurons of the hypothalamic arcuate nucleus that synthesize neuropeptide Y (NPY)/agouti-related protein (AGRP) and α-MSH/cocaine and amphetamine-regulated transcript. Because the central administration of leptin is capable of preventing the inhibitory effects of fasting on TRH mRNA in hypophysiotropic neurons primarily through effects on the arcuate nucleus, we determined whether the continuous administration of 30 mU/d insulin or 648 μg/d glucose into the cerebrospinal f
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Hahn, Tina M., John F. Breininger, Denis G. Baskin, and Michael W. Schwartz. "Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons." Nature Neuroscience 1, no. 4 (1998): 271–72. http://dx.doi.org/10.1038/1082.

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Baldini, Giulia, and Kevin D. Phelan. "The melanocortin pathway and control of appetite-progress and therapeutic implications." Journal of Endocrinology 241, no. 1 (2019): R1—R33. http://dx.doi.org/10.1530/joe-18-0596.

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The initial discovery that ob/ob mice become obese because of a recessive mutation of the leptin gene has been crucial to discover the melanocortin pathway to control appetite. In the melanocortin pathway, the fed state is signaled by abundance of circulating hormones such as leptin and insulin, which bind to receptors expressed at the surface of pro-opiomelanocortin (POMC) neurons to promote processing of POMC to the mature hormone α-melanocyte-stimulating hormone (α-MSH). The α-MSH released by POMC neurons then signals to decrease energy intake by binding to melanocortin-4 receptor (MC4R) ex
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