The Distribution and Mechanism of Action of Ghrelin in the CNS Demonstrates a Novel Hypothalamic Circuit Regulating Energy Homeostasis
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The gastrointestinal peptide hormone ghrelin stimulates appetite in rodents and humans via hypothalamic actions. We discovered expression of ghrelin in a previously uncharacterized group of neurons adjacent to the third ventricle between the dorsal, ventral, paraventricular, and arcuate hypothalamic nuclei. These neurons send efferents onto key hypothalamic circuits, including those producing neuropeptide Y (NPY), Agouti-related protein (AGRP), proopiomelanocortin (POMC) products, and corticotropin-releasing hormone (CRH). Within the hypothalamus, ghrelin bound mostly on presynaptic terminals of NPY neurons. Using electrophysiological recordings, we found that ghrelin stimulated the activity of arcuate NPY neurons and mimicked the effect of NPY in the paraventricular nucleus of the hypothalamus (PVH). We propose that at these sites, release of ghrelin may stimulate the release of orexigenic peptides and neurotransmitters, thus representing a novel regulatory circuit controlling energy homeostasis.
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Ghrelin plays a key role in regulating appetite and energy balance.
“Ghrelin, a neuroprotective hormone secreted by cells in the stomach, plays a key role in regulating the appetite and energy balance of the body [20, 29, 44].”
From Protective PLCG2 variants associate with a delayed onset of Alzheimer’s disease among heterozygous APOE ε4 carriers (2026) · cites this paper as [44]
Ghrelin is a neuroprotective hormone secreted by cells in the stomach.
“Ghrelin, a neuroprotective hormone secreted by cells in the stomach, plays a key role in regulating the appetite and energy balance of the body [20, 29, 44].”
From Protective PLCG2 variants associate with a delayed onset of Alzheimer’s disease among heterozygous APOE ε4 carriers (2026) · cites this paper as [44]
Ghrelin reduces tau phosphorylation.
“It binds to growth hormone secretagogue receptor (GHSR), and it has been shown to protect neurons from β-amyloid-induced toxicity, reduce tau phosphorylation, and enhance synaptic plasticity [20, 44–46].”
From Protective PLCG2 variants associate with a delayed onset of Alzheimer’s disease among heterozygous APOE ε4 carriers (2026) · cites this paper as [44]
Ghrelin protects neurons from β-amyloid-induced toxicity.
“It binds to growth hormone secretagogue receptor (GHSR), and it has been shown to protect neurons from β-amyloid-induced toxicity, reduce tau phosphorylation, and enhance synaptic plasticity [20, 44–46].”
From Protective PLCG2 variants associate with a delayed onset of Alzheimer’s disease among heterozygous APOE ε4 carriers (2026) · cites this paper as [44]
Ghrelin binds to growth hormone secretagogue receptor (GHSR).
“It binds to growth hormone secretagogue receptor (GHSR), and it has been shown to protect neurons from β-amyloid-induced toxicity, reduce tau phosphorylation, and enhance synaptic plasticity [20, 44–46].”
From Protective PLCG2 variants associate with a delayed onset of Alzheimer’s disease among heterozygous APOE ε4 carriers (2026) · cites this paper as [44]
Ghrelin enhances synaptic plasticity.
“It binds to growth hormone secretagogue receptor (GHSR), and it has been shown to protect neurons from β-amyloid-induced toxicity, reduce tau phosphorylation, and enhance synaptic plasticity [20, 44–46].”
From Protective PLCG2 variants associate with a delayed onset of Alzheimer’s disease among heterozygous APOE ε4 carriers (2026) · cites this paper as [44]
Cites
The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity
de Lecea, L., Kilduff, T. S., Peyron, C., Gao, X.-B., Foye, P. E., Danielson, P. E., Fukuhara, C., Battenberg, E. L. F., Gautvik, V. T., Bartlett, F. S., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.1.322 · Cited by 3,878 · see citing works
A role for ghrelin in the central regulation of feeding
Nakazato, M., Murakami, N., Date, Y., Kojima, M., Matsuo, H., Kangawa, K., & Matsukura, S. (2001) · Nature · doi:10.1038/35051587 · Cited by 3,443 · cited 3× · see citing works
“…not be sufficient, however, to account for from the pituitary (Arvat et al., 2001). the potent orexigenic effects of ghrelin (Tschop et al., 2000, 2002; Nakazato et al., 2001; Wren et al., 2001a; Model of Ghrelin Action in the Brain The results outlined here provide both anatomical sub-Kamegai et…”
BackgroundMethodA preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans
Cummings, D. E., Purnell, J. Q., Frayo, R. S., Schmidova, K., Wisse, B. E., & Weigle, D. S. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1714 · Cited by 2,940 · see citing works
Coexpression 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
Leptin Regulation of Neuroendocrine Systems
Ahima, R. S., Saper, C. B., Flier, J. S., & Elmquist, J. K. (2000) · Frontiers in Neuroendocrinology · doi:10.1006/frne.2000.0197 · Cited by 767 · see citing works
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Ghrelin: Structure and Function
Kojima, M., & Kangawa, K. (2005) · Physiological Reviews · doi:10.1152/physrev.00012.2004 · Cited by 2,810 · see citing works
Obesity and Metabolic Syndrome in Circadian <i>Clock</i> Mutant Mice
Turek, F. W., Joshu, C., Kohsaka, A., Lin, E., Ivanova, G., McDearmon, E., Laposky, A., Losee-Olson, S., Easton, A., Jensen, D. R., et al. (2005) · Science · doi:10.1126/science.1108750 · Cited by 2,485 · see citing works
Anatomy and regulation of the central melanocortin system
Cone, R. D. (2005) · Nature Neuroscience · doi:10.1038/nn1455 · Cited by 1,583 · see citing works
Self-citationThe role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review
Klok, M. D., Jakobsdottir, S., & Drent, M. L. (2007) · Obesity Reviews · doi:10.1111/j.1467-789x.2006.00270.x · Cited by 1,442 · see citing works
Biological, Physiological, Pathophysiological, and Pharmacological Aspects of Ghrelin
van der Lely, A. J., Tschöp, M., Heiman, M. L., & Ghigo, E. (2004) · Endocrine Reviews · doi:10.1210/er.2002-0029 · Cited by 1,187 · see citing works
Self-citationExpression of ghrelin receptor mRNA in the rat and the mouse brain
Zigman, J. M., Jones, J. E., Lee, C. E., Saper, C. B., & Elmquist, J. K. (2006) · The Journal of Comparative Neurology · doi:10.1002/cne.20823 · Cited by 1,074 · see citing works
Müller, T. D., Nogueiras, R., Andermann, M. L., Andrews, Z. B., Anker, S. D., Argente, J., Batterham, R. L., Benoit, S. C., Bowers, C. Y., Broglio, F., et al. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.03.005 · Cited by 1,034 · see citing works
Self-citationDeconstruction of a neural circuit for hunger
Atasoy, D., Betley, J. N., Su, H. H., & Sternson, S. M. (2012) · Nature · doi:10.1038/nature11270 · Cited by 969 · see citing works
Abizaid, A., Liu, Z.-W., Andrews, Z. B., Shanabrough, M., Borok, E., Elsworth, J. D., Roth, R. H., Sleeman, M. W., Picciotto, M. R., Tschöp, M. H., et al. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29867 · Cited by 984 · see citing works
Self-citationThe role of the gut microbiota in energy metabolism and metabolic disease
Cani, P., & Delzenne, N. (2009) · Current Pharmaceutical Design · doi:10.2174/138161209788168164 · Cited by 974 · see citing works
Ghrelin controls hippocampal spine synapse density and memory performance
Diano, S., Farr, S. A., Benoit, S. C., McNay, E. C., da Silva, I., Horvath, B., Gaskin, F. S., Nonaka, N., Jaeger, L. B., Banks, W. A., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1656 · Cited by 828 · see citing works
Self-citationNeurobiology of food intake in health and disease
Morton, G. J., Meek, T. H., & Schwartz, M. W. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3745 · Cited by 748 · see citing works
UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals
Andrews, Z. B., Liu, Z.-W., Walllingford, N., Erion, D. M., Borok, E., Friedman, J. M., Tschöp, M. H., Shanabrough, M., Cline, G., Shulman, G. I., et al. (2008) · Nature · doi:10.1038/nature07181 · Cited by 710 · see citing works
Self-citationGhrelin Modulates Brain Activity in Areas that Control Appetitive Behavior
Malik, S., McGlone, F., Bedrossian, D., & Dagher, A. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.03.007 · Cited by 677 · see citing works
Sensory Detection of Food Rapidly Modulates Arcuate Feeding Circuits
Chen, Y., Lin, Y.-C., Kuo, T.-W., & Knight, Z. A. (2015) · Cell · doi:10.1016/j.cell.2015.01.033 · Cited by 660 · see citing works
Ghrelin and the short- and long-term regulation of appetite and body weight
Cummings, D. E. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.05.022 · Cited by 620 · see citing works
Studies 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
Self-citationAnxiety, depression, and the microbiome: A role for gut peptides
Lach, G., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2018) · Neurotherapeutics · doi:10.1007/s13311-017-0585-0 · Cited by 573 · see citing works
Winsky-Sommerer, R., Yamanaka, A., Diano, S., Borok, E., Roberts, A. J., Sakurai, T., Kilduff, T. S., Horvath, T. L., & de Lecea, L. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.3459-04.2004 · Cited by 462 · see citing works
Self-citationGhrelin action in the brain controls adipocyte metabolism
Theander-Carrillo, C. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25811 · Cited by 465 · see citing works
The circadian regulation of food intake
Challet, E. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0210-x · Cited by 428 · see citing works
Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus
van den Top, M., Lee, K., Whyment, A. D., Blanks, A. M., & Spanswick, D. (2004) · Nature Neuroscience · doi:10.1038/nn1226 · Cited by 435 · see citing works
Jerlhag, E., Egecioglu, E., Dickson, S. L., Douhan, A., Svensson, L., & Engel, J. A. (2007) · Addiction Biology · doi:10.1111/j.1369-1600.2006.00041.x · Cited by 431 · see citing works
Naleid, A. M., Grace, M. K., Cummings, D. E., & Levine, A. S. (2005) · Peptides · doi:10.1016/j.peptides.2005.04.025 · Cited by 409 · see citing works
LEAP2 Is an Endogenous Antagonist of the Ghrelin Receptor
Ge, X., Yang, H., Bednarek, M. A., Galon-Tilleman, H., Chen, P., Chen, M., Lichtman, J. S., Wang, Y., Dalmas, O., Yin, Y., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.10.016 · Cited by 376 · see citing works
Hormonal regulation of food intake
Stanley, S., Wynne, K., McGowan, B., & Bloom, S. (2005) · Physiological Reviews · doi:10.1152/physrev.00015.2004 · Cited by 372 · see citing works
Neurobiology of Feeding and Energy Expenditure
Gao, Q., & Horvath, T. L. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094324 · Cited by 346 · see citing works
Central effects of estradiol in the regulation of food intake, body weight, and adiposity
Brown, L. M., & Clegg, D. J. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2009.12.005 · Cited by 331 · see citing works
Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding
Kim, J. G., Suyama, S., Koch, M., Jin, S., Argente-Arizon, P., Argente, J., Liu, Z.-W., Zimmer, M. R., Jeong, J. K., Szigeti-Buck, K., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3725 · Cited by 336 · see citing works
Self-citationCannabinoids, opioids and eating behavior: The molecular face of hedonism?
Cota, D., Tschöp, M. H., Horvath, T. L., & Levine, A. S. (2006) · Brain Research Reviews · doi:10.1016/j.brainresrev.2005.10.004 · Cited by 330 · see citing works
Self-citationRapid sensing of circulating ghrelin by hypothalamic appetite-modifying neurons
Schaeffer, M., Langlet, F., Lafont, C., Molino, F., Hodson, D. J., Roux, T., Lamarque, L., Verdié, P., Bourrier, E., Dehouck, B., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1212137110 · Cited by 325 · see citing works
Diet-Induced Obesity Causes Ghrelin Resistance in Arcuate NPY/AgRP Neurons
Briggs, D. I., Enriori, P. J., Lemus, M. B., Cowley, M. A., & Andrews, Z. B. (2010) · Endocrinology · doi:10.1210/en.2010-0556 · Cited by 320 · see citing works
Self-citationHypothalamic Survival Circuits: Blueprints for Purposive Behaviors
Sternson, S. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.018 · Cited by 313 · see citing works
Liu, T., Kong, D., Shah, B. P., Ye, C., Koda, S., Saunders, A., Ding, J. B., Yang, Z., Sabatini, B. L., & Lowell, B. B. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.027 · Cited by 296 · see citing works
Coppola, A., Liu, Z.-W., Andrews, Z. B., Paradis, E., Roy, M.-C., Friedman, J. M., Ricquier, D., Richard, D., Horvath, T. L., Gao, X.-B., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2006.12.002 · Cited by 295 · see citing works
Self-citationAndrews, Z. B., Erion, D., Beiler, R., Liu, Z.-W., Abizaid, A., Zigman, J., Elsworth, J. D., Savitt, J. M., DiMarchi, R., Tschöp, M., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3890-09.2009 · Cited by 289 · see citing works
Self-citationFrom gut microbiota to host appetite: gut microbiota-derived metabolites as key regulators
Han, H., Yi, B., Zhong, R., Wang, M., Zhang, S., Ma, J., Yin, Y., Yin, J., Chen, L., & Zhang, H. (2021) · Microbiome · doi:10.1186/s40168-021-01093-y · Cited by 292 · see citing works
Serotonin activates the hypothalamic–Pituitary–Adrenal axis via serotonin 2C receptor stimulation
Heisler, L. K., Pronchuk, N., Nonogaki, K., Zhou, L., Raber, J., Tung, L., Yeo, G. S. H., O'Rahilly, S., Colmers, W. F., Elmquist, J. K., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2584-06.2007 · Cited by 292 · see citing works
Self-citationRole of the gut-brain axis in energy and glucose metabolism
Wachsmuth, H. R., Weninger, S. N., & Duca, F. A. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00677-w · Cited by 269 · see citing works
Franssen, R., Monajemi, H., Stroes, E. S. G., & Kastelein, J. J. P. (2011) · Medical Clinics of North America · doi:10.1016/j.mcna.2011.06.003 · Cited by 270 · see citing works
Hypothalamic control of energy balance: insights into the role of synaptic plasticity
Dietrich, M. O., & Horvath, T. L. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2012.12.005 · Cited by 227 · see citing works
Self-citationTang-Christensen, M., Vrang, N., Ortmann, S., Bidlingmaier, M., Horvath, T. L., & Tschöp, M. (2004) · Endocrinology · doi:10.1210/en.2004-0529 · Cited by 226 · see citing works
Self-citationThe physiology of gastric emptying
Hellström, P. M., Grybäck, P., & Jacobsson, H. (2006) · Best Practice & Research Clinical Anaesthesiology · doi:10.1016/j.bpa.2006.02.002 · Cited by 223 · see citing works
Adriaenssens, A. E., Svendsen, B., Lam, B. Y. H., Yeo, G. S. H., Holst, J. J., Reimann, F., & Gribble, F. M. (2016) · Diabetologia · doi:10.1007/s00125-016-4033-1 · Cited by 223 · see citing works
Hunger neurons drive feeding through a sustained, positive reinforcement signal.
Chen, Y., Lin, Y.-C., Zimmerman, C. A., Essner, R. A., & Knight, Z. A. (2016) · eLife · doi:10.7554/elife.18640 · Cited by 196 · see citing works
Garcia, A. L., Otto, B., Reich, S.-C., Weickert, M. O., Steiniger, J., Machowetz, A., Rudovich, N. N., Möhlig, M., Katz, N., Speth, M., et al. (2007) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602525 · Cited by 203 · see citing works
Baver, S. B., Hope, K., Guyot, S., Bjørbaek, C., Kaczorowski, C., & O'Connell, K. M. S. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.4861-12.2014 · Cited by 203 · see citing works
Bouret, S., Levin, B. E., & Ozanne, S. E. (2015) · Physiological Reviews · doi:10.1152/physrev.00007.2014 · Cited by 157 · see citing works
Estrogen as a key regulator of energy homeostasis and metabolic health
Mahboobifard, F., Pourgholami, M. H., Jorjani, M., Dargahi, L., Amiri, M., Sadeghi, S., & Tehrani, F. R. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113808 · Cited by 154 · see citing works
Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis
Rahmouni, K. (2014) · Hypertension · doi:10.1161/hypertensionaha.114.00920 · Cited by 150 · see citing works
Neural Control and Modulation of Thirst, Sodium Appetite, and Hunger
Augustine, V., Lee, S., & Oka, Y. (2020) · Cell · doi:10.1016/j.cell.2019.11.040 · Cited by 135 · see citing works
Serotonin and the regulation of mammalian energy balance
Donovan, M. H., & Tecott, L. H. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00036 · Cited by 150 · 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
Self-citationNeuroanatomical Pathways for Thyroid Hormone Feedback in the Human Hypothalamus
Alkemade, A., Friesema, E. C., Unmehopa, U. A., Fabriek, B. O., Kuiper, G. G., Leonard, J. L., Wiersinga, W. M., Swaab, D. F., Visser, T. J., & Fliers, E. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-2567 · Cited by 146 · see citing works
The intestine as an endocrine organ and the role of gut hormones in metabolic regulation
Bany Bakar, R., Reimann, F., & Gribble, F. M. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00830-y · Cited by 144 · see citing works
Hippocampal dopamine/DRD1 signaling dependent on the ghrelin receptor
Kern, A., Mavrikaki, M., Ullrich, C., Albarran-Zeckler, R., Brantley, A. F., & Smith, R. G. (2015) · Cell · doi:10.1016/j.cell.2015.10.062 · Cited by 136 · see citing works
Spencer, S. J., Emmerzaal, T. L., Kozicz, T., & Andrews, Z. B. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.10.021 · Cited by 129 · 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
Current Understanding of the Hypothalamic Ghrelin Pathways Inducing Appetite and Adiposity
Al Massadi, O., López, M., Tschöp, M., Diéguez, C., & Nogueiras, R. (2017) · Trends in Neurosciences · doi:10.1016/j.tins.2016.12.003 · Cited by 124 · see citing works
Self-citationFunctional implications of glutamatergic projections to the ventral tegmental area
Geisler, S., & Wise, R. A. (2008) · Reviews in the Neurosciences · doi:10.1515/revneuro.2008.19.4-5.227 · Cited by 125 · see citing works
Ghrelin is an orexigenic and metabolic signaling peptide in the arcuate and paraventricular nuclei
Currie, P. J., Mirza, A., Fuld, R., Park, D., & Vasselli, J. R. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00756.2004 · Cited by 125 · see citing works
Kishi, 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
Actions and therapeutic pathways of ghrelin for gastrointestinal disorders
Camilleri, M., Papathanasopoulos, A., & Odunsi, S. T. (2009) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2009.72 · Cited by 115 · see citing works
Huang, H.-J., Zhu, X.-C., Han, Q.-Q., Wang, Y.-L., Yue, N., Wang, J., Yu, R., Li, B., Wu, G.-C., Liu, Q., et al. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.02.040 · Cited by 114 · see citing works
Rhea, E. M., Salameh, T. S., Gray, S., Niu, J., Banks, W. A., & Tong, J. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.09.007 · Cited by 114 · see citing works
Lanfranco, F., Bonelli, L., Baldi, M., Me, E., Broglio, F., & Ghigo, E. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0049 · Cited by 112 · see citing works
Wiedmer, P., Nogueiras, R., Broglio, F., D'Alessio, D., & Tschöp, M. H. (2007) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0625 · Cited by 111 · see citing works
Self-citationHanlon, E. C., & Van Cauter, E. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1101338108 · Cited by 110 · see citing works
Neural circuits and motivational processes for hunger
Sternson, S. M., Nicholas Betley, J., & Cao, Z. F. H. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.04.006 · Cited by 108 · see citing works
Peptide hormone ghrelin enhances neuronal excitability by inhibition of Kv7/KCNQ channels
Shi, L., Bian, X., Qu, Z., Ma, Z., Zhou, Y., Wang, K., Jiang, H., & Xie, J. (2013) · Nature Communications · doi:10.1038/ncomms2439 · Cited by 103 · see citing works
Hunger and Satiety Gauge Reward Sensitivity
Cassidy, R. M., & Tong, Q. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00104 · Cited by 93 · see citing works
Altered brain response to drinking glucose and fructose in obese adolescents
Jastreboff, A. M., Sinha, R., Arora, J., Giannini, C., Kubat, J., Malik, S., Van Name, M. A., Santoro, N., Savoye, M., Duran, E. J., et al. (2016) · Diabetes · doi:10.2337/db15-1216 · Cited by 97 · see citing works
Chronobiology, endocrinology, and energy‐ and food‐reward homeostasis
Gonnissen, H. K. J., Hulshof, T., & Westerterp‐Plantenga, M. S. (2013) · Obesity Reviews · doi:10.1111/obr.12019 · Cited by 93 · see citing works
Allaway, H. C. M., Southmayd, E. A., & De Souza, M. J. (2016) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2015-0053 · Cited by 89 · see citing works
Analysis of brain nuclei accessible to ghrelin present in the cerebrospinal fluid
Cabral, A., Fernandez, G., & Perello, M. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.09.008 · Cited by 83 · see citing works
Gut-derived signaling molecules and vagal afferents in the control of glucose and energy homeostasis
Thorens, B., & Larsen, P. J. (2004) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/01.mco.0000134368.91900.84 · Cited by 73 · see citing works
Huang, H., Xu, Y., & van den Pol, A. N. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00740.2010 · Cited by 70 · see citing works
A Hypothalamic Phosphatase Switch Coordinates Energy Expenditure with Feeding
Dodd, G. T., Andrews, Z. B., Simonds, S. E., Michael, N. J., DeVeer, M., Brüning, J. C., Spanswick, D., Cowley, M. A., & Tiganis, T. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.07.013 · Cited by 66 · see citing works
Self-citationThe neurological effects of ghrelin in brain diseases: Beyond metabolic functions
Jiao, Q., Du, X., Li, Y., Gong, B., Shi, L., Tang, T., & Jiang, H. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.12.010 · Cited by 62 · see citing works
Suda, Y., Kuzumaki, N., Sone, T., Narita, M., Tanaka, K., Hamada, Y., Iwasawa, C., Shibasaki, M., Maekawa, A., Matsuo, M., et al. (2018) · Molecular Brain · doi:10.1186/s13041-018-0349-8 · Cited by 60 · see citing works
Brain control of energy homeostasis: implications for anti-obesity pharmacotherapy
Johansen, V. B. I., Petersen, J., Lund, J., Mathiesen, C. V., Fenselau, H., & Clemmensen, C. (2025) · Cell · doi:10.1016/j.cell.2025.06.010 · Cited by 53 · see citing works
If Body Fatness is Under Physiological Regulation, Then How Come We Have an Obesity Epidemic?
Speakman, J. R. (2014) · Physiology · doi:10.1152/physiol.00053.2013 · Cited by 53 · see citing works
The hormonal signature of energy deficit: Increasing the value of food reward
Lockie, S. H., & Andrews, Z. B. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.08.003 · Cited by 50 · see citing works
The central melanocortin system and the regulation of energy balance
Lee, M. (2007) · Frontiers in Bioscience · doi:10.2741/2366 · Cited by 45 · see citing works
Feng, D. D., Yang, S.-K., Loudes, C., Simon, A., Al-Sarraf, T., Culler, M., Alvear-Perez, R., Llorens-Cortes, C., Chen, C., Epelbaum, J., et al. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07787.x · Cited by 41 · see citing works
Ghrelin in neuroendocrine organs and tumours
Leontiou, C. A., Franchi, G., & Korbonits, M. (2007) · Pituitary · doi:10.1007/s11102-007-0023-0 · Cited by 40 · see citing works
Stievenard, A., Méquinion, M., Andrews, Z. B., Destée, A., Chartier-Harlin, M.-C., Viltart, O., & Vanbesien-Mailliot, C. C. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.11.021 · Cited by 39 · see citing works
Liu, T., Ji, R.-L., & Tao, Y.-X. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.108044 · Cited by 34 · see citing works
Ghrelin’s Role as a Major Regulator of Appetite and Its Other Functions in Neuroendocrinology
Lim, C. T., Kola, B., Korbonits, M., & Grossman, A. B. (2010) · Progress in Brain Research · doi:10.1016/s0079-6123(10)82008-4 · Cited by 34 · see citing works
Lampropoulos, C., Alexandrides, T., Tsochatzis, S., Kehagias, D., & Kehagias, I. (2021) · Obesity Surgery · doi:10.1007/s11695-021-05568-7 · Cited by 30 · see citing works
An overview of anamorelin as a treatment option for cancer-associated anorexia and cachexia
Fonseca, G. W. P. D., & von Haehling, S. (2021) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2021.1873954 · Cited by 25 · see citing works
Yang, J. A., Mamounis, K. J., Yasrebi, A., & Roepke, T. A. (2016) · Steroids · doi:10.1016/j.steroids.2016.01.003 · Cited by 21 · see citing works
Michael, N. J., Simonds, S. E., van den Top, M., Cowley, M. A., & Spanswick, D. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.07.002 · Cited by 21 · see citing works
Self-citationPérez de la Mora, M., Borroto-Escuela, D. O., Crespo-Ramírez, M., Rejón-Orantes, J. D. C., Palacios-Lagunas, D. A., Martínez-Mata, M. K., Sánchez-Luna, D., Tesoro-Cruz, E., & Fuxe, K. (2022) · Cells · doi:10.3390/cells11111826 · Cited by 21 · see citing works
“Sibling” battle or harmony: Crosstalk between nesfatin-1 and ghrelin
Chen, X., Dong, J., Jiao, Q., Du, X., Bi, M., & Jiang, H. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04193-6 · Cited by 17 · see citing works
Iranmanesh, A., Bowers, C. Y., & Veldhuis, J. D. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0205 · Cited by 10 · see citing works
Hypothalamic Regulation of Anterior Pituitary Function
Ben-Shlomo, A., & Melmed, S. (2017) · The Pituitary · doi:10.1016/b978-0-12-804169-7.00002-7 · Cited by 11 · see citing works
Jeskanen, H., Heikkinen, S., Kervinen, I., Lehtisalo, J., Ngandu, T., Willman, R.-M., Rosa, J., Hoffmann, D., FinnGen, Leinonen, V., et al. (2026) · Alzheimer's Research & Therapy · doi:10.1186/s13195-026-01957-1 · Cited by 1 · see citing works
“Ghrelin, a neuroprotective hormone secreted by cells in the stomach, plays a key role in regulating the appetite and energy balance of the body [20, 29, 44].”
- Authors
- Cowley, M. A., Smith, R. G., Diano, S., Tschöp, M., Pronchuk, N., Grove, K. L., Strasburger, C. J., Bidlingmaier, M., Esterman, M., Heiman, M. L., Garcia-Segura, L. M., Nillni, E. A., Mendez, P., Low, M. J., Sotonyi, P., Friedman, J. M., Liu, H., Pinto, S., Colmers, W. F., Cone, R. D., & Horvath, T. L.
- Affiliations
- Oregon Health & Science University (US)
- Baylor College of Medicine (US)
- Yale University (US)
- Eli Lilly (United States) (US)
- University of Alberta (CA)
- Oregon National Primate Research Center (US)
- Brown University (US)
- Rockefeller University (US)
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 37
- Issue
- 4
- Pages
- 649-661
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1990095603
- Cited by
- 1,679
- References
- 5
- Citations by year
- 2026: 15 · 2025: 49 · 2024: 41 · 2023: 46 · 2022: 57 · 2021: 77 · 2020: 64 · 2019: 47 · 2018: 66 · 2017: 78 · 2016: 90 · 2015: 67 · 2014: 89 · 2013: 90 · 2012: 102
- FWCI
- 36.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3819 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- National Institutes of Health (AG-018895, DK-51730, DK-60711, DK-61619, DK-62202, MH-59847, RR-14451)
- Merck
- Canadian Institutes of Health Research (MT 10520)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- ghrelin, hypothalamus, energy homeostasis, neuropeptide Y, arcuate nucleus, paraventricular nucleus, third ventricle, appetite, orexigenic peptides, presynaptic terminals, corticotropin-releasing factor, proopiomelanocortin, agouti-related protein, hypothalamic circuitry
- MeSH terms
- Animals, Central Nervous System, Corticotropin-Releasing Hormone, Energy Metabolism, Female, Homeostasis, Hypothalamus, Luminescent Proteins, Mice, Transgenic, Nerve Net, Neurons, Neuropeptide Y, Organ Specificity, Paraventricular Hypothalamic Nucleus, Pro-Opiomelanocortin, Protein Binding, Proteins, Protein Biosynthesis, Presynaptic Terminals, Mice, Knockout, Patch-Clamp Techniques, Intercellular Signaling Peptides and Proteins, Peptide Hormones, Mice, Rats, Agouti-Related Protein, Ghrelin, In Vitro Techniques
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