Current Understanding of the Hypothalamic Ghrelin Pathways Inducing Appetite and Adiposity

Al Massadi, Omar; López, Miguel; Tschöp, Matthias; Diéguez, Carlos; Nogueiras, Ruben

doi:10.1016/j.tins.2016.12.003

Cited by 124Regulation of Appetite and ObesityHypothalamic control of reproductive hormonesAdipokines, Inflammation, and Metabolic Diseases

Current Understanding of the Hypothalamic Ghrelin Pathways Inducing Appetite and Adiposity

Al Massadi, Omar, López, Miguel, Tschöp, Matthias, Diéguez, Carlos, Nogueiras, Ruben·2017·Trends in Neurosciences

DOI 10.1016/j.tins.2016.12.003

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Abstract

Ghrelin is a multifaceted regulator of metabolism. Ghrelin regulates energy balance in the short term via induction of appetite and in the long term via increased body weight and adiposity. Recently, several central pathways modulating the metabolic actions of ghrelin were unmasked, and it was shown to act through different hypothalamic nuclei to induce feeding. Ghrelin also modulates glucose homeostasis, but the central mechanisms responsible for this action have not been studied in detail. Although ghrelin also acts through extrahypothalamic areas to promote feeding, this review specifically dissects hypothalamic control of ghrelin's orexigenic and adipogenic actions and presents current understanding of the intracellular ghrelin orexigenic pathways, including their dependence on other relevant systems implicated in energy balance.

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Ghrelin can directly promote adiposity, independently of food intake or GH secretion, by increasing carbohydrate use, stimulating lipid synthesis, and reducing fatty acid oxidation.
“Moreover, ghrelin can directly promote adiposity, independently of food intake or GH secretion, by increasing carbohydrate use, stimulating lipid synthesis, and reducing fatty acid oxidation 50, 52.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [50]

Ghrelin is a growth-hormone-releasing acylated peptide from stomach
Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., & Kangawa, K. (1999) · Nature · doi:10.1038/45230 · Cited by 8,479 · see citing works
Ghrelin induces adiposity in rodents
Tschöp, M., Smiley, D. L., & Heiman, M. L. (2000) · Nature · doi:10.1038/35038090 · Cited by 3,949 · see citing works
Self-citation
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
“However, soon after its discovery, its ability to induce food intake and adiposity was reported [5,6].”
Ghrelin enhances appetite and increases food intake in humans
Wren, A. M., Seal, L. J., Cohen, M. A., Brynes, A. E., Frost, G. S., Murphy, K. G., Dhillo, W. S., Ghatei, M. A., & Bloom, S. R. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.12.8111 · Cited by 2,494 · see citing works
The Distribution and Mechanism of Action of Ghrelin in the CNS Demonstrates a Novel Hypothalamic Circuit Regulating Energy Homeostasis
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., et al. (2003) · Neuron · doi:10.1016/s0896-6273(03)00063-1 · Cited by 1,679 · see citing works
Self-citation
The Novel Hypothalamic Peptide Ghrelin Stimulates Food Intake and Growth Hormone Secretion
Wren, A. M., Small, C. J., Ward, H. L., Murphy, K. G., Dakin, C. L., Taheri, S., Kennedy, A. R., Roberts, G. H., Morgan, D. G. A., Ghatei, M. A., et al. (2000) · Endocrinology · doi:10.1210/endo.141.11.7873 · Cited by 1,593 · see citing works
Hypothalamic mTOR Signaling Regulates Food Intake
Cota, D., Proulx, K., Smith, K. A. B., Kozma, S. C., Thomas, G., Woods, S. C., & Seeley, R. J. (2006) · Science · doi:10.1126/science.1124147 · Cited by 1,278 · see citing works
Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone.
Yang, J., Brown, M. S., Liang, G., Grishin, N., & Goldstein, J. (2008) · Cell · doi:10.1016/j.cell.2008.01.017 · Cited by 1,191 · see citing works
Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues.
Guan, X.-M., Yu, H., Palyha, O., McKee, K., Feighner, S., Sirinathsinghji, D., Smith, R. G., van der Ploeg, L., & Howard, A. (1997) · Brain Research. Molecular Brain Research · doi:10.1016/s0169-328x(97)00071-5 · Cited by 1,185 · see citing works
AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training
Aponte, Y., Atasoy, D., & Sternson, S. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2739 · Cited by 1,157 · see citing works
NPY/AgRP Neurons Are Essential for Feeding in Adult Mice but Can Be Ablated in Neonates
Luquet, S. H., Perez, F. A., Hnasko, T. S., & Palmiter, R. D. (2005) · Science · doi:10.1126/science.1115524 · Cited by 1,127 · see citing works
Obesity Wars
Flier, J. S. (2004) · Cell · doi:10.1016/s0092-8674(03)01081-x · Cited by 1,105 · see citing works
Expression 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
Ghrelin
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-citation
Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite
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-citation
Ghrelin octanoylation mediated by an orphan lipid transferase
Gutierrez, J. A., Solenberg, P., Perkins, D., Willency, J. A., Knierman, M. D., Jin, Z., Witcher, D., Luo, S., Onyia, J. E., & Hale, J. (2008) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0800708105 · Cited by 827 · see citing works
Sirtuin 1 and Sirtuin 3: Physiological Modulators of Metabolism
Nogueiras, R., Habegger, K. M., Chaudhary, N., Finan, B., Banks, A. S., Dietrich, M. O., Horváth, T. L., Sinclair, D. A., Pfluger, P. T., & Tschöp, M. H. (2012) · Physiological Reviews · doi:10.1152/physrev.00022.2011 · Cited by 712 · see citing works
Self-citation
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-citation
Orexigenic Action of Peripheral Ghrelin Is Mediated by Neuropeptide Y and Agouti-Related Protein
Chen, H. Y., Trumbauer, M. E., Chen, A. S., Weingarth, D. T., Adams, J. R., Frazier, E. G., Shen, Z., Marsh, D. J., Feighner, S. D., Guan, X.-M., et al. (2004) · Endocrinology · doi:10.1210/en.2003-1596 · Cited by 667 · see citing works
Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission
Alex, K. D., & Pehek, E. A. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2006.08.004 · Cited by 658 · see citing works
Mice lacking ghrelin receptors resist the development of diet-induced obesity
Zigman, J. M. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26002 · Cited by 654 · see citing works
Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production
Obici, S., Feng, Z., Arduini, A., Conti, R., & Rossetti, L. (2003) · Nature Medicine · doi:10.1038/nm873 · Cited by 548 · see citing works
Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin
Asakawa, A., Inui, A., Fujimiya, M., Sakamaki, R., Shinfuku, N., Ueta, Y., Meguid, M. M., & Kasuga, M. (2004) · Gut · doi:10.1136/gut.2004.038737 · Cited by 483 · see citing works
Cannabinoids and Ghrelin Have Both Central and Peripheral Metabolic and Cardiac Effects via AMP-activated Protein Kinase
Kola, B., Hubina, E., Tucci, S. A., Kirkham, T. C., García, E., Mitchell, S. E., Williams, L. M., Hawley, S. A., Hardie, D. G., Grossman, A. B., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500175200 · Cited by 468 · see citing works
Hypothalamic Fatty Acid Metabolism Mediates the Orexigenic Action of Ghrelin
López, M., Lage, R., Saha, A. K., Pérez–Tilve, D., Vazquez, M. J., Varela, L., Sangiao‐Alvarellos, S., Tovar, S. A., Raghay, K., Rodríguez‐Cuenca, S., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.03.006 · Cited by 466 · see citing works
Self-citation
Ghrelin 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
Ghrelin-Induced Food Intake Is Mediated via the Orexin Pathway
Toshinai, K., Date, Y., Murakami, N., Shimada, M., Mondal, M. S., Shimbara, T., Guan, J., Wang, Q., Funahashi, H., Sakurai, T., et al. (2003) · Endocrinology · doi:10.1210/en.2002-220788 · Cited by 462 · see citing works
Hunger States Switch a Flip-Flop Memory Circuit via a Synaptic AMPK-Dependent Positive Feedback Loop
Yang, Y., Atasoy, D., Su, H. H., & Sternson, S. M. (2011) · Cell · doi:10.1016/j.cell.2011.07.039 · Cited by 431 · see citing works
Ghrelin O -acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice
Zhao, T., Liang, G., Li, R. L., Xie, X., Sleeman, M. W., Murphy, A. J., Valenzuela, D. M., Yancopoulos, G. D., Goldstein, J. L., & Brown, M. S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002271107 · Cited by 427 · see citing works
Hypothalamic CaMKK2 Contributes to the Regulation of Energy Balance
Anderson, K. A., Ribar, T. J., Lin, F., Noeldner, P. K., Green, M. F., Muehlbauer, M. J., Witters, L. A., Kemp, B. E., & Means, A. R. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.02.011 · Cited by 385 · see citing works
Des-Acyl Ghrelin Induces Food Intake by a Mechanism Independent of the Growth Hormone Secretagogue Receptor
Toshinai, K., Yamaguchi, H., Sun, Y., Smith, R. G., Yamanaka, A., Sakurai, T., Date, Y., Mondal, M. S., Shimbara, T., Kawagoe, T., et al. (2006) · Endocrinology · doi:10.1210/en.2005-1357 · Cited by 375 · see citing works
Absence of ghrelin protects against early-onset obesity
Wortley, K. E. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26003 · Cited by 375 · see citing works
Ablation of ghrelin improves the diabetic but not obese phenotype of ob/ob mice.
Sun, Y.-X., Asnicar, M., Saha, P., Chan, L., & Smith, R. G. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.04.004 · Cited by 368 · see citing works
Rapid 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
Apo-Ghrelin Receptor Forms Heteromers with DRD2 in Hypothalamic Neurons and Is Essential for Anorexigenic Effects of DRD2 Agonism
Kern, A., Albarran-Zeckler, R. G., Walsh, H. E., & Smith, R. G. (2012) · Neuron · doi:10.1016/j.neuron.2011.10.038 · Cited by 316 · see citing works
Hypothalamic AMPK: a canonical regulator of whole-body energy balance
López, M., Nogueiras, R., Tena‐Sempere, M., & Diéguez, C. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.67 · Cited by 312 · see citing works
Self-citation
The Orexigenic Effect of Ghrelin Is Mediated through Central Activation of the Endogenous Cannabinoid System
Kola, B., Farkas, I., Christ‐Crain, M., Wittmann, G., Lolli, F., Amin, F., Harvey-White, J. D., Liposits, Z., Kunos, G., Grossman, A. B., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001797 · Cited by 295 · see citing works
Ghrelin amplifies dopamine signaling by cross talk involving formation of growth hormone secretagogue receptor/dopamine receptor subtype 1 heterodimers.
Jiang, H., Betancourt, L., & Smith, R. G. (2006) · Molecular Endocrinology · doi:10.1210/me.2005-0084 · Cited by 279 · see citing works
Ghrelin-induced growth hormone secretion in humans
Peino, R., Baldelli, R., Rodríguez, J., Rodríguez‐Segade, S., Kojima, M., Kangawa, K., Arvat, E., Ghigo, E., Diéguez, C., & Casanueva, F. F. (2000) · European Journal of Endocrinology · doi:10.1530/eje.0.143r011 · Cited by 277 · see citing works
Self-citation
Characterization of Adult Ghrelin and Ghrelin Receptor Knockout Mice under Positive and Negative Energy Balance
Sun, Y., Butte, N. F., Garcia, J. M., & Smith, R. G. (2007) · Endocrinology · doi:10.1210/en.2007-0271 · Cited by 274 · see citing works
Arcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin
Wang, Q., Liu, C., Uchida, A., Chuang, J.-C., Walker, A. K., Liu, T., Osborne-Lawrence, S. L., Mason, B. L., Mosher, C. A., Berglund, E. D., et al. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.10.001 · Cited by 246 · see citing works
Astrocytes Control Food Intake by Inhibiting AGRP Neuron Activity via Adenosine A1 Receptors
Yang, L., Qi, Y., & Yang, Y. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.002 · Cited by 242 · see citing works
Agouti-Related Peptide, Neuropeptide Y, and Somatostatin-Producing Neurons Are Targets for Ghrelin Actions in the Rat Hypothalamus
Seoane, L. M., López, M., Tovar, S. A., Casanueva, F. F., Señarís, R. M., & Diéguez, C. (2003) · Endocrinology · doi:10.1210/en.2002-220795 · Cited by 228 · see citing works
Self-citation
Des-acyl Ghrelin Acts by CRF Type 2 Receptors to Disrupt Fasted Stomach Motility in Conscious Rats
Chen, C., Inui, A., Asakawa, A., Fujino, K., Kato, I., Chen, C.-C., Ueno, N., & Fujimiya, M. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.04.015 · Cited by 227 · see citing works
Ghrelin Acts as an Interface between Physiological State and Phasic Dopamine Signaling
Cone, J. J., McCutcheon, J. E., & Roitman, M. F. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.4404-13.2014 · Cited by 185 · see citing works
Key Role for AMP-Activated Protein Kinase in the Ventromedial Hypothalamus in Regulating Counterregulatory Hormone Responses to Acute Hypoglycemia
McCrimmon, R. J., Shaw, M., Fan, X., Cheng, H. M., Ding, Y., Vella, M. C., Zhou, L., McNay, E. C., & Sherwin, R. S. (2007) · Diabetes · doi:10.2337/db07-0837 · Cited by 172 · see citing works
Ghrelin Signalling on Food Reward: A Salient Link Between the Gut and the Mesolimbic System
Perelló, M., & Dickson, S. L. (2014) · Journal of Neuroendocrinology · doi:10.1111/jne.12236 · Cited by 170 · see citing works
Pharmacological targeting of the serotonergic system for the treatment of obesity
Garfield, A. S., & Heisler, L. K. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.164152 · Cited by 170 · see citing works
Palatability Can Drive Feeding Independent of AgRP Neurons
Denis, R. G. P., Joly-Amado, A., Webber, E., Langlet, F., Schaeffer, M., Padilla, S. L., Cansell, C., Dehouck, B., Castel, J., Delbès, A.-S., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.07.011 · Cited by 164 · see citing works
The Central Sirtuin 1/p53 Pathway Is Essential for the Orexigenic Action of Ghrelin
Velásquez, D. A., Martínez, G., Romero, A., Vázquez, M. J., Boit, K. D., Dopeso-Reyes, I. G., López, M., Vidal, A., Nogueiras, R., & Diéguez, C. (2011) · Diabetes · doi:10.2337/db10-0802 · Cited by 161 · see citing works
Self-citation
Ghrelin-AMPK Signaling Mediates the Neuroprotective Effects of Calorie Restriction in Parkinson's Disease
Bayliss, J. A., Lemus, M. B., Stark, R., dos Santos, V. V., Thompson, A., Rees, D. J., Galić, S., Elsworth, J. D., Kemp, B. E., Davies, J. S., et al. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.4373-15.2016 · Cited by 161 · see citing works
Neonatal overnutrition causes early alterations in the central response to peripheral ghrelin
Colldén, G., Balland, É., Parkash, J., Caron, É., Langlet, F., Prévot, V., & Bouret, S. G. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.10.003 · Cited by 156 · see citing works
Neonatal ghrelin programs development of hypothalamic feeding circuits
Steculorum, S. M., Colldén, G., Coupé, B., Croizier, S., Lockie, S. H., Andrews, Z. B., Jarosch, F., Klußmann, S., & Bouret, S. G. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73688 · Cited by 154 · see citing works
Obesity Impairs the Action of the Neuroendocrine Ghrelin System
Zigman, J. M., Bouret, S. G., & Andrews, Z. B. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.09.010 · Cited by 153 · see citing works
Promiscuous Dimerization of the Growth Hormone Secretagogue Receptor (GHS-R1a) Attenuates Ghrelin-mediated Signaling
Schellekens, H., van Oeffelen, W. E. P. A., Dinan, T. G., & Cryan, J. F. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.382473 · Cited by 153 · see citing works
Induced Ablation of Ghrelin Cells in Adult Mice Does Not Decrease Food Intake, Body Weight, or Response to High-Fat Diet
McFarlane, M., Brown, M. S., Goldstein, J. L., & Zhao, T. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.04.007 · Cited by 150 · see citing works
Potential Role for AMP-Activated Protein Kinase in Hypoglycemia Sensing in the Ventromedial Hypothalamus
McCrimmon, R. J., Fan, X., Ding, Y., Zhu, W., Jacob, R. J., & Sherwin, R. S. (2004) · Diabetes · doi:10.2337/diabetes.53.8.1953 · Cited by 148 · see citing works
Transgenic Mice Overexpressing Des-Acyl Ghrelin Show Small Phenotype
Ariyasu, H., Takaya, K., Iwakura, H., Hosoda, H., Akamizu, T., Arai, Y., Kangawa, K., & Nakao, K. (2004) · Endocrinology · doi:10.1210/en.2004-0629 · Cited by 147 · see citing works
Effect of Des-acyl Ghrelin on Adiposity and Glucose Metabolism
Zhang, W., Chai, B., Li, J.-Y., Wang, H., & Mulholland, M. W. (2008) · Endocrinology · doi:10.1210/en.2008-0263 · Cited by 136 · 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
Resistance to the orexigenic effect of ghrelin in dietary-induced obesity in mice: reversal upon weight loss
Perreault, M., Istrate, N., Wang, L., Nichols, A., Tozzo, E., & Stricker‐Krongrad, A. (2004) · International Journal of Obesity · doi:10.1038/sj.ijo.0802640 · Cited by 132 · see citing works
Ghrelin‐induced adiposity is independent of orexigenic effects
Perez-Tilve, D., Heppner, K., Kirchner, H., Lockie, S. K. H., Woods, S. C., Smiley, D., Tschöp, M., & Pfluger, P. (2011) · The FASEB Journal · doi:10.1096/fj.11-183632 · Cited by 132 · see citing works
Self-citation
Hypothalamic mTOR Signaling Mediates the Orexigenic Action of Ghrelin
Martins, L., Fernández-Mallo, D., Novelle, M. G., Vazquez, M. J., Tena‐Sempere, M., Nogueiras, R., López, M., & Diéguez, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046923 · Cited by 131 · see citing works
Self-citation
Profound Hypoglycemia in Starved, Ghrelin-deficient Mice Is Caused by Decreased Gluconeogenesis and Reversed by Lactate or Fatty Acids
Li, R. L., Sherbet, D. P., Elsbernd, B. L., Goldstein, J. L., Brown, M. S., & Zhao, T. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.358051 · Cited by 127 · see citing works
Hypothalamic AMPK-induced autophagy increases food intake by regulating NPY and POMC expression
Oh, T. S., Cho, H., Cho, J. H., Yu, S.-W., & Kim, E. K. (2016) · Autophagy · doi:10.1080/15548627.2016.1215382 · Cited by 121 · see citing works
Both Acyl and Des-Acyl Ghrelin Regulate Adiposity and Glucose Metabolism via Central Nervous System Ghrelin Receptors
Heppner, K. M., Piechowski, C. L., Müller, A., Ottaway, N., Sisley, S. R., Smiley, D. L., Habegger, K. M., Pfluger, P. T., DiMarchi, R. D., Biebermann, H., et al. (2013) · Diabetes · doi:10.2337/db13-0414 · Cited by 120 · see citing works
Self-citation
Effects of ghrelin and amylin on dopamine, norepinephrine and serotonin release in the hypothalamus
Brunetti, L., Recinella, L., Orlando, G., Michelotto, B., Nisio, C. D., & Vacca, M. (2002) · European Journal of Pharmacology · doi:10.1016/s0014-2999(02)02552-9 · Cited by 119 · see citing works
Ghrelin’s Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction
Schellekens, H., Francesco, P. N. D., Kandil, D., Theeuwes, W. F., McCarthy, T., van Oeffelen, W. E. P. A., Perelló, M., Giblin, L. M., Dinan, T. G., & Cryan, J. F. (2015) · ACS Chemical Neuroscience · doi:10.1021/cn500318q · Cited by 117 · see citing works
Hippocampus ghrelin signaling mediates appetite through lateral hypothalamic orexin pathways
Hsu, T. M., Hahn, J. D., Konanur, V., Noble, E. E., Suarez, A. N., Thai, J. B., Nakamoto, E. M., & Kanoski, S. E. (2015) · eLife · doi:10.7554/elife.11190 · Cited by 115 · see citing works
Mutually Opposite Signal Modulation by Hypothalamic Heterodimerization of Ghrelin and Melanocortin-3 Receptors
Rediger, A., Piechowski, C. L., Yi, C., Tarnow, P., Strotmann, R., Grüters, A., Krude, H., Schöneberg, T., Tschöp, M. H., Kleinau, G., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.287607 · Cited by 112 · see citing works
Self-citation
Activation of AMP-Activated Protein Kinase Within the Ventromedial Hypothalamus Amplifies Counterregulatory Hormone Responses in Rats With Defective Counterregulation
McCrimmon, R. J., Fan, X., Cheng, H. M., McNay, E. C., Chan, O. T. M., Shaw, M., Ding, Y., Zhu, W., & Sherwin, R. S. (2006) · Diabetes · doi:10.2337/db05-1359 · Cited by 112 · see citing works
Divergent Neuronal Circuitries Underlying Acute Orexigenic Effects of Peripheral or Central Ghrelin: Critical Role of Brain Accessibility
Cabral, A., Valdivia, S., Fernández, G., Reynaldo, M. B., & Perelló, M. (2014) · Journal of Neuroendocrinology · doi:10.1111/jne.12168 · Cited by 109 · see citing works
Hypothalamic Control of Lipid Metabolism: Focus on Leptin, Ghrelin and Melanocortins
Diéguez, C., Vazquez, M. J., Romero, A., López, M., & Nogueiras, R. (2011) · Neuroendocrinology · doi:10.1159/000328122 · Cited by 105 · see citing works
Self-citation
Melanocortin signaling in the CNS directly regulates circulating cholesterol
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Authors: Al Massadi, O., López, M., Tschöp, M., Diéguez, C., & Nogueiras, R.
Affiliations: Universidade de Santiago de Compostela (ES)
Helmholtz Munich (DE)
ORCID: López, Miguel
Tschöp, Matthias
Diéguez, Carlos
Venue: Trends in Neurosciences
Publisher: Elsevier BV
Published: 2017-03
Volume: 40
Issue: 3
Pages: 167-180
ISSN: 0166-2236 (ISSN-L)
DOI: 10.1016/j.tins.2016.12.003
OpenAlex: W2571988049
Cited by: 124
References: 104
Citations by year: 2026: 5 · 2025: 12 · 2024: 10 · 2023: 12 · 2022: 17 · 2021: 14 · 2020: 19 · 2019: 13 · 2018: 11 · 2017: 11
FWCI: 1.79
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Neurosciences (publishedVersion)
PubMed (publishedVersion)
mediaTUM (Technical University of Munich) (submittedVersion)
Site cant be reached (submittedVersion)
PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords: ghrelin, hypothalamus, appetite, adiposity, energy balance, feeding behavior, glucose homeostasis, intracellular signaling, hypothalamic nuclei
MeSH terms: Animals, Appetite, Glucose, Humans, Hypothalamus, Adiposity, Ghrelin

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Current Understanding of the Hypothalamic Ghrelin Pathways Inducing Appetite and Adiposity

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