Review

. 2015 Mar 21;4(6):437-60.

doi: 10.1016/j.molmet.2015.03.005. eCollection 2015 Jun.

Ghrelin

T D Müller¹, R Nogueiras², M L Andermann³, Z B Andrews⁴, S D Anker⁵, J Argente⁶, R L Batterham⁷, S C Benoit⁸, C Y Bowers⁹, F Broglio¹⁰, F F Casanueva¹¹, D D'Alessio¹², I Depoortere¹³, A Geliebter¹⁴, E Ghigo¹⁵, P A Cole¹⁶, M Cowley¹⁷, D E Cummings¹⁸, A Dagher¹⁹, S Diano²⁰, S L Dickson²¹, C Diéguez²², R Granata¹⁰, H J Grill²³, K Grove²⁴, K M Habegger²⁵, K Heppner²⁶, M L Heiman²⁷, L Holsen²⁸, B Holst²⁹, A Inui³⁰, J O Jansson³¹, H Kirchner³², M Korbonits³³, B Laferrère³⁴, C W LeRoux³⁵, M Lopez², S Morin¹, M Nakazato³⁶, R Nass³⁷, D Perez-Tilve³⁸, P T Pfluger¹, T W Schwartz³⁹, R J Seeley⁴⁰, M Sleeman⁴, Y Sun⁴¹, L Sussel⁴², J Tong¹², M O Thorner³⁷, A J van der Lely⁴³, L H T van der Ploeg⁴⁴, J M Zigman⁴⁵, M Kojima⁴⁶, K Kangawa⁴⁷, R G Smith⁴⁸, T Horvath⁴⁹, M H Tschöp⁵⁰

Affiliations

¹ Institute for Diabetes and Obesity, Helmholtz Zentrum München, München, Germany.
² Department of Physiology, Centro de Investigación en Medicina Molecular y Enfermedades Crónicas, University of Santiago de Compostela (CIMUS)-Instituto de Investigación Sanitaria (IDIS)-CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain.
³ Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁴ Department of Physiology, Faculty of Medicine, Monash University, Melbourne, Victoria, Australia.
⁵ Applied Cachexia Research, Department of Cardiology, Charité Universitätsmedizin Berlin, Germany.
⁶ Department of Pediatrics and Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain ; Department of Pediatrics, Universidad Autónoma de Madrid and CIBER Fisiopatología de la obesidad y nutrición, Instituto de Salud Carlos III, Madrid, Spain.
⁷ Centre for Obesity Research, University College London, London, United Kingdom.
⁸ Metabolic Disease Institute, Division of Endocrinology, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
⁹ Tulane University Health Sciences Center, Endocrinology and Metabolism Section, Peptide Research Section, New Orleans, LA, USA.
¹⁰ Division of Endocrinology, Diabetes and Metabolism, Dept. of Medical Sciences, University of Torino, Torino, Italy.
¹¹ Department of Medicine, Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago (CHUS), CIBER de Fisiopatologia Obesidad y Nutricion (CB06/03), Instituto Salud Carlos III, Santiago de Compostela, Spain.
¹² Duke Molecular Physiology Institute, Duke University, Durham, NC, USA.
¹³ Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
¹⁴ New York Obesity Nutrition Research Center, Department of Medicine, St Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY, USA.
¹⁵ Department of Pharmacology & Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁶ Monash Obesity & Diabetes Institute, Monash University, Clayton, Victoria, Australia.
¹⁷ Department of Physiology, Faculty of Medicine, Monash University, Melbourne, Victoria, Australia ; Monash Obesity & Diabetes Institute, Monash University, Clayton, Victoria, Australia.
¹⁸ Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
¹⁹ McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
²⁰ Dept of Neurobiology, Yale University School of Medicine, New Haven, CT, USA.
²¹ Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
²² Department of Physiology, School of Medicine, Instituto de Investigacion Sanitaria (IDIS), University of Santiago de Compostela, Spain.
²³ Department of Psychology, Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA.
²⁴ Department of Diabetes, Obesity and Metabolism, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
²⁵ Comprehensive Diabetes Center, University of Alabama School of Medicine, Birmingham, AL, USA.
²⁶ Division of Diabetes, Obesity, and Metabolism, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
²⁷ NuMe Health, 1441 Canal Street, New Orleans, LA 70112, USA.
²⁸ Departments of Psychiatry and Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
²⁹ Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen N, Denmark.
³⁰ Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
³¹ Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
³² Medizinische Klinik I, Universitätsklinikum Schleswig-Holstein Campus Lübeck, Lübeck, Germany.
³³ Centre for Endocrinology, William Harvey Research Institute, Barts and the London, Queen Mary University of London, London, UK.
³⁴ New York Obesity Research Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
³⁵ Diabetes Complications Research Centre, Conway Institute, University College Dublin, Ireland.
³⁶ Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan.
³⁷ Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA, USA.
³⁸ Department of Internal Medicine, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
³⁹ Department of Neuroscience and Pharmacology, Laboratory for Molecular Pharmacology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
⁴⁰ Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA.
⁴¹ Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
⁴² Department of Genetics and Development, Columbia University, New York, NY, USA.
⁴³ Department of Medicine, Erasmus University MC, Rotterdam, The Netherlands.
⁴⁴ Rhythm Pharmaceuticals, Boston, MA, USA.
⁴⁵ Departments of Internal Medicine and Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁴⁶ Molecular Genetics, Institute of Life Science, Kurume University, Kurume, Japan.
⁴⁷ National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
⁴⁸ The Scripps Research Institute, Florida Department of Metabolism & Aging, Jupiter, FL, USA.
⁴⁹ Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
⁵⁰ Institute for Diabetes and Obesity, Helmholtz Zentrum München, München, Germany ; Division of Metabolic Diseases, Department of Medicine, Technical University Munich, Munich, Germany.

PMID: 26042199
PMCID: PMC4443295
DOI: 10.1016/j.molmet.2015.03.005

Review

Ghrelin

T D Müller et al. Mol Metab. 2015.

. 2015 Mar 21;4(6):437-60.

doi: 10.1016/j.molmet.2015.03.005. eCollection 2015 Jun.

Authors

Affiliations

¹ Institute for Diabetes and Obesity, Helmholtz Zentrum München, München, Germany.
² Department of Physiology, Centro de Investigación en Medicina Molecular y Enfermedades Crónicas, University of Santiago de Compostela (CIMUS)-Instituto de Investigación Sanitaria (IDIS)-CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain.
³ Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁴ Department of Physiology, Faculty of Medicine, Monash University, Melbourne, Victoria, Australia.
⁵ Applied Cachexia Research, Department of Cardiology, Charité Universitätsmedizin Berlin, Germany.
⁶ Department of Pediatrics and Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain ; Department of Pediatrics, Universidad Autónoma de Madrid and CIBER Fisiopatología de la obesidad y nutrición, Instituto de Salud Carlos III, Madrid, Spain.
⁷ Centre for Obesity Research, University College London, London, United Kingdom.
⁸ Metabolic Disease Institute, Division of Endocrinology, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
⁹ Tulane University Health Sciences Center, Endocrinology and Metabolism Section, Peptide Research Section, New Orleans, LA, USA.
¹⁰ Division of Endocrinology, Diabetes and Metabolism, Dept. of Medical Sciences, University of Torino, Torino, Italy.
¹¹ Department of Medicine, Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago (CHUS), CIBER de Fisiopatologia Obesidad y Nutricion (CB06/03), Instituto Salud Carlos III, Santiago de Compostela, Spain.
¹² Duke Molecular Physiology Institute, Duke University, Durham, NC, USA.
¹³ Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
¹⁴ New York Obesity Nutrition Research Center, Department of Medicine, St Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY, USA.
¹⁵ Department of Pharmacology & Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁶ Monash Obesity & Diabetes Institute, Monash University, Clayton, Victoria, Australia.
¹⁷ Department of Physiology, Faculty of Medicine, Monash University, Melbourne, Victoria, Australia ; Monash Obesity & Diabetes Institute, Monash University, Clayton, Victoria, Australia.
¹⁸ Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
¹⁹ McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
²⁰ Dept of Neurobiology, Yale University School of Medicine, New Haven, CT, USA.
²¹ Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
²² Department of Physiology, School of Medicine, Instituto de Investigacion Sanitaria (IDIS), University of Santiago de Compostela, Spain.
²³ Department of Psychology, Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA.
²⁴ Department of Diabetes, Obesity and Metabolism, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
²⁵ Comprehensive Diabetes Center, University of Alabama School of Medicine, Birmingham, AL, USA.
²⁶ Division of Diabetes, Obesity, and Metabolism, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
²⁷ NuMe Health, 1441 Canal Street, New Orleans, LA 70112, USA.
²⁸ Departments of Psychiatry and Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
²⁹ Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen N, Denmark.
³⁰ Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
³¹ Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
³² Medizinische Klinik I, Universitätsklinikum Schleswig-Holstein Campus Lübeck, Lübeck, Germany.
³³ Centre for Endocrinology, William Harvey Research Institute, Barts and the London, Queen Mary University of London, London, UK.
³⁴ New York Obesity Research Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
³⁵ Diabetes Complications Research Centre, Conway Institute, University College Dublin, Ireland.
³⁶ Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan.
³⁷ Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA, USA.
³⁸ Department of Internal Medicine, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
³⁹ Department of Neuroscience and Pharmacology, Laboratory for Molecular Pharmacology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
⁴⁰ Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA.
⁴¹ Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
⁴² Department of Genetics and Development, Columbia University, New York, NY, USA.
⁴³ Department of Medicine, Erasmus University MC, Rotterdam, The Netherlands.
⁴⁴ Rhythm Pharmaceuticals, Boston, MA, USA.
⁴⁵ Departments of Internal Medicine and Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁴⁶ Molecular Genetics, Institute of Life Science, Kurume University, Kurume, Japan.
⁴⁷ National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
⁴⁸ The Scripps Research Institute, Florida Department of Metabolism & Aging, Jupiter, FL, USA.
⁴⁹ Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
⁵⁰ Institute for Diabetes and Obesity, Helmholtz Zentrum München, München, Germany ; Division of Metabolic Diseases, Department of Medicine, Technical University Munich, Munich, Germany.

PMID: 26042199
PMCID: PMC4443295
DOI: 10.1016/j.molmet.2015.03.005

Abstract

Background: The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism.

Scope of review: In this review, we discuss the diverse biological functions of ghrelin, the regulation of its secretion, and address questions that still remain 15 years after its discovery.

Major conclusions: In recent years, ghrelin has been found to have a plethora of central and peripheral actions in distinct areas including learning and memory, gut motility and gastric acid secretion, sleep/wake rhythm, reward seeking behavior, taste sensation and glucose metabolism.

Keywords: Ghrelin; Growth hormone segretagogue receptor.

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Figures

**Figure 1**
Schematic on ghrelin's physiological effects.

**Figure 2**
Schematic on the post-translational processing and acylation of ghrelin.

**Figure 3**
Milestones in ghrelin research. Bar graph represents the number of publications listed in the US National Library of Medicine National Institute of Health (PubMed) and that contain the word ‘ghrelin’ in either the title or the abstract until December 2014.

**Figure 4**
Schematic overview of the 7TM receptors judged to be either stimulating (in green to the right) or inhibiting (red or orange to the left and top) ghrelin secretion directly on the ghrelin cell. The main signaling pathway (Gαs or Gαi) employed by each of the receptors in the ghrelin cell is indicated inside the receptor in black. Figure taken from Engelstoft et al., Mol Metab. 2013 .

See this image and copyright information in PMC

References

1. Kojima M., Hosoda H., Date Y., Nakazato M., Matsuo H., Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402:656–660. - PubMed
1. Tschop M., Smiley D.L., Heiman M.L. Ghrelin induces adiposity in rodents. Nature. 2000;407:908–913. - PubMed
1. Cowley M.A., Smith R.G., Diano S., Tschop M., Pronchuk N., Grove K.L. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron. 2003;37:649–661. - PubMed
1. Nakazato M., Murakami N., Date Y., Kojima M., Matsuo H., Kangawa K. A role for ghrelin in the central regulation of feeding. Nature. 2001;409:194–198. - PubMed
1. Masuda Y., Tanaka T., Inomata N., Ohnuma N., Tanaka S., Itoh Z. Ghrelin stimulates gastric acid secretion and motility in rats. Biochemical and Biophysical Research Communications. 2000;276:905–908. - PubMed

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Ghrelin

Affiliations

Ghrelin

Authors

Affiliations

Abstract

Figures

References

Publication types

Grants and funding

LinkOut - more resources

Full Text Sources

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Research Materials