View source for Ghrelin

{{Short description|Peptide hormone involved in appetite regulation}}
{{Use dmy dates|date=March 2016}}
{{Infobox gene}}

'''Ghrelin''' ({{IPAc-en|ˈ|ɡ|r|ɛ|l|ɪ|n}}; or '''lenomorelin''', [[International Nonproprietary Name|INN]]) is a [[hormone]] primarily produced by [[enteroendocrine cells]] of the [[gastrointestinal tract]], especially the stomach,<ref name="Kojima1999">{{cite journal | vauthors = Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K | title = Ghrelin is a growth-hormone-releasing acylated peptide from stomach | journal = Nature | volume = 402 | issue = 6762 | pages = 656–660 | date = December 1999 | pmid = 10604470 | doi = 10.1038/45230 | s2cid = 753383 | bibcode = 1999Natur.402..656K }}</ref><ref name="muller">{{cite journal | vauthors = Müller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD, Argente J, Batterham RL, Benoit SC, Bowers CY, Broglio F, Casanueva FF, D'Alessio D, Depoortere I, Geliebter A, Ghigo E, Cole PA, Cowley M, Cummings DE, Dagher A, Diano S, Dickson SL, Diéguez C, Granata R, Grill HJ, Grove K, Habegger KM, Heppner K, Heiman ML, Holsen L, Holst B, Inui A, Jansson JO, Kirchner H, Korbonits M, Laferrère B, LeRoux CW, Lopez M, Morin S, Nakazato M, Nass R, Perez-Tilve D, Pfluger PT, Schwartz TW, Seeley RJ, Sleeman M, Sun Y, Sussel L, Tong J, Thorner MO, van der Lely AJ, van der Ploeg LH, Zigman JM, Kojima M, Kangawa K, Smith RG, Horvath T, Tschöp MH | display-authors = 6 | title = Ghrelin | journal = Molecular Metabolism | volume = 4 | issue = 6 | pages = 437–460 | date = June 2015 | pmid = 26042199 | pmc = 4443295 | doi = 10.1016/j.molmet.2015.03.005 }}</ref> and is also dubbed the "'''hunger hormone'''" because it increases the drive to eat.<ref name="muller" /> Blood levels of ghrelin are highest before meals when hungry, returning to lower levels after mealtimes.<ref name="muller" /><ref>{{cite journal | vauthors = Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS | title = A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans | journal = Diabetes | volume = 50 | issue = 8 | pages = 1714–1719 | date = August 2001 | pmid = 11473029 | doi = 10.2337/diabetes.50.8.1714 | doi-access = free }}</ref> Ghrelin may help prepare for food intake<ref name="muller" /><ref name = "Schwartz_2000"/> by increasing gastric [[motility]] and stimulating the [[secretion]] of [[gastric acid]].<ref name="muller" />

Ghrelin activates cells in the [[anterior pituitary|anterior pituitary gland]] and [[hypothalamus|hypothalamic]] [[arcuate nucleus]],<ref name="muller" /><ref name="Dickson1993">{{cite journal | vauthors = Dickson SL, Leng G, Robinson IC | title = Systemic administration of growth hormone-releasing peptide activates hypothalamic arcuate neurons | journal = Neuroscience | volume = 53 | issue = 2 | pages = 303–306 | date = March 1993 | pmid = 8492908 | doi = 10.1016/0306-4522(93)90197-n | s2cid = 9757253 }}</ref> including [[neuropeptide Y]] [[neuron]]s that initiate [[appetite]].<ref name="muller" /><ref name="pmid9003014">{{cite journal | vauthors = Dickson SL, Luckman SM | title = Induction of c-fos messenger ribonucleic acid in neuropeptide Y and growth hormone (GH)-releasing factor neurons in the rat arcuate nucleus following systemic injection of the GH secretagogue, GH-releasing peptide-6 | journal = Endocrinology | volume = 138 | issue = 2 | pages = 771–777 | date = February 1997 | pmid = 9003014 | doi = 10.1210/endo.138.2.4907 | doi-access = free }}</ref> Ghrelin stimulates brain structures having a specific [[receptor (biochemistry)|receptor]] &ndash; the [[growth hormone]] [[secretagogue]] receptor 1A ([[GHSR]]-1A).<ref name="muller" /><ref name="Howard1996">{{cite journal | vauthors = Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, Hamelin M, Hreniuk DL, Palyha OC, Anderson J, Paress PS, Diaz C, Chou M, Liu KK, McKee KK, Pong SS, Chaung LY, Elbrecht A, Dashkevicz M, Heavens R, Rigby M, Sirinathsinghji DJ, Dean DC, Melillo DG, Patchett AA, Nargund R, Griffin PR, DeMartino JA, Gupta SK, Schaeffer JM, Smith RG, Van der Ploeg LH | display-authors = 6 | title = A receptor in pituitary and hypothalamus that functions in growth hormone release | journal = Science | volume = 273 | issue = 5277 | pages = 974–977 | date = August 1996 | pmid = 8688086 | doi = 10.1126/science.273.5277.974 | s2cid = 32192383 | bibcode = 1996Sci...273..974H }}</ref> Ghrelin also participates in regulation of reward [[cognition]],<ref name="NHM-Ghrelin">{{cite book |vauthors=Nestler EJ, Hyman SE, Holtzman DM, Malenka RC |title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2015 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0-07-182769-0 | pages = 245–267 | edition = 3rd | chapter = Neural and Neuroendocrine Control of the Internal Milieu }}</ref> learning and [[memory]], [[circadian rhythm|the sleep-wake cycle]], [[taste]] sensation, [[reward system|reward behavior]], and [[glucose metabolism]].<ref name="muller" /><ref name="Cholinergic-dopaminergic reward link">{{cite journal | vauthors = Dickson SL, Egecioglu E, Landgren S, Skibicka KP, Engel JA, Jerlhag E | title = The role of the central ghrelin system in reward from food and chemical drugs | journal = Molecular and Cellular Endocrinology | volume = 340 | issue = 1 | pages = 80–87 | date = June 2011 | pmid = 21354264 | doi = 10.1016/j.mce.2011.02.017 | hdl-access = free | quote = Whereas ghrelin emerged as a stomach-derived hormone involved in energy balance, hunger and meal initiation via hypothalamic circuits, it now seems clear that it also has a role in motivated reward-driven behaviours via activation of the so-called "cholinergic-dopaminergic reward link". | s2cid = 206815322 | hdl = 2077/26318 | url = https://hal.archives-ouvertes.fr/hal-00706318/file/PEER_stage2_10.1016%252Fj.mce.2011.02.017.pdf }}</ref><ref name="Mesocorticolimbic projection">{{cite book | veditors = Davis KL, Charney D, Coyle JT, Nemeroff C | title = Neuropsychopharmacology : the fifth generation of progress: an official publication of the American College of Neuropsychopharmacology | date = 2002 | publisher = Lippincott Williams & Wilkins | location = Philadelphia, Pa. | isbn = 978-0-7817-2837-9 | edition = 5th | author = Le Moal M | chapter = Mesocorticolimbic Dopaminergic Neurons | chapter-url = http://www.acnp.org/g4/gn401000025/ch025.html | access-date = 21 May 2014 | archive-date = 5 February 2018 | archive-url = https://web.archive.org/web/20180205211300/http://www.acnp.org/g4/gn401000025/ch025.html }}</ref>

==History and name==
Ghrelin was discovered after the ghrelin receptor (called growth hormone secretagogue type 1A receptor or GHS-R) was determined in 1999.<ref name=muller/> The hormone name is based on its role as a '''''g'''rowth '''h'''ormone-'''rel'''easing peptide'', with reference to the [[Proto-Indo-European language|Proto-Indo-European]] root ''[[wiktionary:Reconstruction:Proto-Indo-European/gʰreh₁-|gʰre-]]'', meaning "to grow".<ref name=muller/>

==Gene, transcription products, and structure==
[[File:Preproghrelin 1P7X.png|thumb|Preproghrelin (green and blue) and ghrelin (green)]]
The ''GHRL'' gene produces [[mRNA]] which has four [[exon]]s. Five products arise: the first is the 117-amino acid ''preproghrelin''. It is homologous to promotilin; both are members of the [[motilin]] family. It is cleaved to produce ''proghrelin'' which is cleaved to produce an unacylated 28-amino acid  ''ghrelin'' and an acylated ''C-ghrelin''. ''[[Obestatin]]'' is presumed to be  cleaved from  C-ghrelin.<ref name = "pmid19566830">{{cite journal | vauthors = Seim I, Amorim L, Walpole C, Carter S, Chopin LK, Herington AC | title = Ghrelin gene-related peptides: multifunctional endocrine / autocrine modulators in health and disease | journal = Clinical and Experimental Pharmacology & Physiology | volume = 37 | issue = 1 | pages = 125–131 | date = January 2010 | pmid = 19566830 | doi = 10.1111/j.1440-1681.2009.05241.x | s2cid = 21657818 }}</ref>

Ghrelin only becomes active when [[caprylic acid|caprylic (octanoic) acid]] is linked posttranslationally to [[serine]] at the 3-position by the enzyme [[ghrelin O-acyltransferase]] (GOAT) to form a [[proteolipid]]. It is located on the cell membrane of ghrelin cells in the stomach and [[pancreas]].<ref name = "pmid19896496"/> The non-octanoylated form is desacyl ghrelin. It does not activate the GHS-R receptor but does have other effects: cardiac,<ref>{{cite journal | vauthors = Bedendi I, Alloatti G, Marcantoni A, Malan D, Catapano F, Ghé C, Deghenghi R, Ghigo E, Muccioli G | display-authors = 6 | title = Cardiac effects of ghrelin and its endogenous derivatives des-octanoyl ghrelin and des-Gln14-ghrelin | journal = European Journal of Pharmacology | volume = 476 | issue = 1–2 | pages = 87–95 | date = August 2003 | pmid = 12969753 | doi = 10.1016/S0014-2999(03)02083-1 | hdl-access = free | hdl = 2318/125949 | s2cid = 20542064 }}</ref> anti-ghrelin,<ref>{{cite journal | vauthors = Broglio F, Gottero C, Prodam F, Gauna C, Muccioli G, Papotti M, Abribat T, Van Der Lely AJ, Ghigo E | display-authors = 6 | title = Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 89 | issue = 6 | pages = 3062–3065 | date = June 2004 | pmid = 15181099 | doi = 10.1210/jc.2003-031964 | doi-access = free }}</ref> appetite stimulation,<ref>{{cite journal | vauthors = Toshinai K, Yamaguchi H, Sun Y, Smith RG, Yamanaka A, Sakurai T, Date Y, Mondal MS, Shimbara T, Kawagoe T, Murakami N, Miyazato M, Kangawa K, Nakazato M | display-authors = 6 | title = Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor | journal = Endocrinology | volume = 147 | issue = 5 | pages = 2306–2314 | date = May 2006 | pmid = 16484324 | doi = 10.1210/en.2005-1357 | doi-access = free }}</ref> and inhibition of hepatic glucose output.<ref>{{cite journal | vauthors = Gauna C, Delhanty PJ, Hofland LJ, Janssen JA, Broglio F, Ross RJ, Ghigo E, van der Lely AJ | display-authors = 6 | title = Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 90 | issue = 2 | pages = 1055–1060 | date = February 2005 | pmid = 15536157 | doi = 10.1210/jc.2004-1069 | doi-access = free }}</ref> Side-chains other than octanoyl have also been observed: these can also trigger the ghrelin receptor.<ref>{{cite journal | vauthors = Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB | title = Ghrelin--a hormone with multiple functions | journal = Frontiers in Neuroendocrinology | volume = 25 | issue = 1 | pages = 27–68 | date = April 2004 | pmid = 15183037 | doi = 10.1016/j.yfrne.2004.03.002 | s2cid = 24821233 }}</ref>  In particular, decanoyl ghrelin has been found to constitute a significant portion of circulating ghrelin in mice, but as of 2011 its presence in humans has not been established.<ref name = "Stengel_Tache_2011" >{{cite journal | vauthors = Stengel A, Taché Y | title = Interaction between gastric and upper small intestinal hormones in the regulation of hunger and satiety: ghrelin and cholecystokinin take the central stage | journal = Current Protein & Peptide Science | volume = 12 | issue = 4 | pages = 293–304 | date = June 2011 | pmid = 21428875 | pmc = 3670092 | doi = 10.2174/138920311795906673 }}</ref>

==Ghrelin cells==

===Alternative names===
The ghrelin cell is also known as an A-like cell (pancreas), X-cell (for unknown function), X/A-like cell (rats), Epsilon cell (pancreas), P/D sub 1 cell (humans) and Gr cell (abbreviation for ghrelin cell).<ref name="pmid16322794">{{cite journal | vauthors = Zigman JM, Nakano Y, Coppari R, Balthasar N, Marcus JN, Lee CE, Jones JE, Deysher AE, Waxman AR, White RD, Williams TD, Lachey JL, Seeley RJ, Lowell BB, Elmquist JK | display-authors = 6 | title = Mice lacking ghrelin receptors resist the development of diet-induced obesity | journal = The Journal of Clinical Investigation | volume = 115 | issue = 12 | pages = 3564–3572 | date = December 2005 | pmid = 16322794 | pmc = 1297251 | doi = 10.1172/JCI26002 }}</ref>

===Location===
Ghrelin cells are found mainly in the stomach<ref name = "pmid11600536">{{cite journal | vauthors = Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T, Suda M, Koh T, Natsui K, Toyooka S, Shirakami G, Usui T, Shimatsu A, Doi K, Hosoda H, Kojima M, Kangawa K, Nakao K | display-authors = 6 | title = Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 86 | issue = 10 | pages = 4753–4758 | date = October 2001 | pmid = 11600536 | doi = 10.1210/jcem.86.10.7885 | doi-access = free }}</ref> and duodenum, but also in the jejunum, lungs, pancreatic islets,<ref name="pmid18508724">{{cite journal | vauthors = Suckale J, Solimena M | title = Pancreas islets in metabolic signaling--focus on the beta-cell | journal = Frontiers in Bioscience | volume = 13 | issue = 13 | pages = 7156–7171 | date = May 2008 | pmid = 18508724 | doi = 10.2741/3218 | s2cid = 646106 | doi-access = free }}</ref> gonads, adrenal cortex, placenta, and kidney. It has also been shown that ghrelin is produced locally in the brain.<ref>{{cite journal | vauthors = Ferrini F, Salio C, Lossi L, Merighi A | title = Ghrelin in central neurons | journal = Current Neuropharmacology | volume = 7 | issue = 1 | pages = 37–49 | date = March 2009 | pmid = 19721816 | pmc = 2724662 | doi = 10.2174/157015909787602779 }}</ref> Additionally, research suggests that ghrelin may be produced in the myocardium and have an 'autocrine/ paracrine' like effect within the heart.<ref name="Ghrelin and cardiovascular diseases">{{cite journal | vauthors = Zhang G, Yin X, Qi Y, Pendyala L, Chen J, Hou D, Tang C | title = Ghrelin and cardiovascular diseases | journal = Current Cardiology Reviews | volume = 6 | issue = 1 | pages = 62–70 | date = February 2010 | pmid = 21286280 | pmc = 2845796 | doi = 10.2174/157340310790231662 }}</ref>

Ghrelin cells are also found in [[parietal cells|oxyntic glands]] (20% of cells),<ref name="pmid2470131">{{cite journal | vauthors = Simonsson M, Eriksson S, Håkanson R, Lind T, Lönroth H, Lundell L, O'Connor DT, Sundler F | display-authors = 6 | title = Endocrine cells in the human oxyntic mucosa. A histochemical study | journal = Scandinavian Journal of Gastroenterology | volume = 23 | issue = 9 | pages = 1089–1099 | date = November 1988 | pmid = 2470131 | doi = 10.3109/00365528809090174 }}</ref> [[pyloric glands]], and small intestine.

===Features===
They are ovoid cells with granules.<ref name="pmid94030">{{cite journal | vauthors = Grube D, Forssmann WG | title = Morphology and function of the entero-endocrine cells | journal = Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et Métabolisme | volume = 11 | issue = 11 | pages = 589–606 | date = November 1979 | pmid = 94030 | doi = 10.1055/s-0028-1092785 | s2cid = 40287472 }}</ref> They have [[gastrin]] receptors.<ref name="pmid18611393">{{cite journal | vauthors = Fukumoto K, Nakahara K, Katayama T, Miyazatao M, Kangawa K, Murakami N | title = Synergistic action of gastrin and ghrelin on gastric acid secretion in rats | journal = Biochemical and Biophysical Research Communications | volume = 374 | issue = 1 | pages = 60–63 | date = September 2008 | pmid = 18611393 | doi = 10.1016/j.bbrc.2008.06.114 | bibcode = 2008BBRC..374...60F }}</ref> Some produce [[nesfatin-1]].<ref name="pmid19961888">{{cite journal | vauthors = Inhoff T, Stengel A, Peter L, Goebel M, Taché Y, Bannert N, Wiedenmann B, Klapp BF, Mönnikes H, Kobelt P | display-authors = 6 | title = Novel insight in distribution of nesfatin-1 and phospho-mTOR in the arcuate nucleus of the hypothalamus of rats | journal = Peptides | volume = 31 | issue = 2 | pages = 257–262 | date = February 2010 | pmid = 19961888 | pmc = 4043136 | doi = 10.1016/j.peptides.2009.11.024 }}</ref> Ghrelin cells are not terminally differentiated in the pancreas: they are progenitor cells that can give rise to A-cells, PP cells and Beta-cells there.<ref name="pmid23251675">{{cite journal | vauthors = Arnes L, Hill JT, Gross S, Magnuson MA, Sussel L | title = Ghrelin expression in the mouse pancreas defines a unique multipotent progenitor population | journal = PLOS ONE | volume = 7 | issue = 12 | article-number = e52026 | year = 2012 | pmid = 23251675 | pmc = 3520898 | doi = 10.1371/journal.pone.0052026 | doi-access = free | bibcode = 2012PLoSO...752026A }}</ref>

==Function and mechanism of action{{anchor|Cholinergic–dopaminergic reward link}}==
Ghrelin is a participant in regulating the complex process of [[energy homeostasis]] which adjusts both ''energy input'' – by adjusting hunger signals – and ''energy output'' – by adjusting the proportion of energy going to [[Adenosine triphosphate|ATP]] production, fat storage, glycogen storage, and short-term heat loss. The net result of these processes is reflected in body weight, and is under continuous monitoring and adjustment based on metabolic signals and needs. At any given moment in time, it may be in equilibrium or disequilibrium. Gastric-brain communication is an essential part of energy homeostasis, and several communication pathways are probable, including the gastric intracellular [[Mechanistic target of rapamycin|mTOR]]/[[P70-S6 Kinase 1|S6K1]] pathway mediating the interaction among ghrelin, [[nesfatin]] and [[endocannabinoid]] gastric systems,<ref name="pmid24732927">{{cite book |vauthors=Folgueira C, Seoane LM, Casanueva FF |chapter=The Brain-Stomach Connection |year=2014  |editor1=Delhanty PJD |editor2=van der Lely AJ |title=How Gut and Brain Control Metabolism |series= Frontiers of Hormone Research |volume= 42 |location= Basel |publisher= Karger |pages= 83–92 |doi= 10.1159/000358316 |isbn= 978-3-318-02638-2 |pmid=24732927 |hdl=20.500.11940/4604 }}</ref> and both afferent and efferent vagal signals.

Ghrelin and synthetic ghrelin mimetics ([[growth hormone secretagogue]]s) increase body weight and fat mass<ref>{{cite journal | vauthors = Lall S, Tung LY, Ohlsson C, Jansson JO, Dickson SL | title = Growth hormone (GH)-independent stimulation of adiposity by GH secretagogues | journal = Biochemical and Biophysical Research Communications | volume = 280 | issue = 1 | pages = 132–138 | date = January 2001 | pmid = 11162489 | doi = 10.1006/bbrc.2000.4065 | bibcode = 2001BBRC..280..132L }}</ref><ref>{{cite journal | vauthors = Tschöp M, Smiley DL, Heiman ML | title = Ghrelin induces adiposity in rodents | journal = Nature | volume = 407 | issue = 6806 | pages = 908–913 | date = October 2000 | pmid = 11057670 | doi = 10.1038/35038090 | s2cid = 4564644 | bibcode = 2000Natur.407..908T | author-link1 = Matthias H. Tschöp }}</ref><ref name="pmid27095593">{{cite journal | vauthors = Chebani Y, Marion C, Zizzari P, Chettab K, Pastor M, Korostelev M, Geny D, Epelbaum J, Tolle V, Morisset-Lopez S, Pantel J | display-authors = 6 | title = Enhanced responsiveness of Ghsr Q343X rats to ghrelin results in enhanced adiposity without increased appetite | journal = Science Signaling | volume = 9 | issue = 424 | pages = ra39 | date = April 2016 | pmid = 27095593 | doi = 10.1126/scisignal.aae0374 | s2cid = 29245906 | url = https://www.hal.inserm.fr/inserm-01463897/file/aae0374_ArticleContent_v13_proofs_FOR%20HAL.pdf }}</ref> by triggering receptors in the [[arcuate nucleus]]<ref name="Dickson1993" /> that include [[neuropeptide Y]] (NPY) and [[agouti-related peptide|agouti-related protein]] (AgRP) neurons.<ref name="pmid14962995">{{cite journal | vauthors = Chen HY, Trumbauer ME, Chen AS, Weingarth DT, Adams JR, Frazier EG, Shen Z, Marsh DJ, Feighner SD, Guan XM, Ye Z, Nargund RP, Smith RG, Van der Ploeg LH, Howard AD, MacNeil DJ, Qian S | display-authors = 6 | title = Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein | journal = Endocrinology | volume = 145 | issue = 6 | pages = 2607–2612 | date = June 2004 | pmid = 14962995 | doi = 10.1210/en.2003-1596 | doi-access = free }}</ref><ref name="pmid9003014" /> Ghrelin-responsiveness of these neurons is both leptin- and insulin-sensitive.<ref name = "pmid12453894">{{cite journal | vauthors = Hewson AK, Tung LY, Connell DW, Tookman L, Dickson SL | title = The rat arcuate nucleus integrates peripheral signals provided by leptin, insulin, and a ghrelin mimetic | journal = Diabetes | volume = 51 | issue = 12 | pages = 3412–3419 | date = December 2002 | pmid = 12453894 | doi = 10.2337/diabetes.51.12.3412 | doi-access = free }}</ref> Ghrelin reduces the sensitivity of gastric [[Vagus nerve|vagal]] [[afferent nerve fiber|afferents]], so they are less sensitive to gastric distension.<ref name = "pmid17290011" />

In addition to its function in energy homeostasis, ghrelin also activates the '''cholinergic–dopaminergic reward link'''<!--This is the target of a section redirect on this topic, so this term is bolded per MOS:BOLD#Other uses.--> in inputs to the [[ventral tegmental area]] and in the [[mesolimbic pathway]],<ref name="pmid16137788">{{cite journal | vauthors = Naleid AM, Grace MK, Cummings DE, Levine AS | title = Ghrelin induces feeding in the mesolimbic reward pathway between the ventral tegmental area and the nucleus accumbens | journal = Peptides | volume = 26 | issue = 11 | pages = 2274–2279 | date = November 2005 | pmid = 16137788 | doi = 10.1016/j.peptides.2005.04.025 | s2cid = 25619880 }}</ref> a circuit that communicates the hedonic and reinforcing aspects of natural rewards,<ref name="Cholinergic-dopaminergic reward link"/> such as food and addictive drugs such as ethanol.<ref name = "pmid12453894" /><ref>{{cite journal | vauthors = Jerlhag E, Egecioglu E, Dickson SL, Andersson M, Svensson L, Engel JA | title = Ghrelin stimulates locomotor activity and accumbal dopamine-overflow via central cholinergic systems in mice: implications for its involvement in brain reward | journal = Addiction Biology | volume = 11 | issue = 1 | pages = 45–54 | date = March 2006 | pmid = 16759336 | doi = 10.1111/j.1369-1600.2006.00002.x | s2cid = 33650732 }}</ref><ref>{{cite journal | vauthors = Jerlhag E, Egecioglu E, Dickson SL, Douhan A, Svensson L, Engel JA | title = Ghrelin administration into tegmental areas stimulates locomotor activity and increases extracellular concentration of dopamine in the nucleus accumbens | journal = Addiction Biology | volume = 12 | issue = 1 | pages = 6–16 | date = March 2007 | pmid = 17407492 | doi = 10.1111/j.1369-1600.2006.00041.x | s2cid = 22556527 }}</ref> Ghrelin receptors are located on neurons in this circuit.<ref name="Cholinergic-dopaminergic reward link" /><ref name="NHM-Ghrelin"/> Hypothalamic ghrelin signalling is required for reward from alcohol<ref name = "pmid19564604">{{cite journal | vauthors = Jerlhag E, Egecioglu E, Landgren S, Salomé N, Heilig M, Moechars D, Datta R, Perrissoud D, Dickson SL, Engel JA | display-authors = 6 | title = Requirement of central ghrelin signaling for alcohol reward | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 27 | pages = 11318–11323 | date = July 2009 | pmid = 19564604 | pmc = 2703665 | doi = 10.1073/pnas.0812809106 | doi-access = free | bibcode = 2009PNAS..10611318J }}</ref> and palatable/rewarding foods.<ref name = "pmid20477752">{{cite journal | vauthors = Egecioglu E, Jerlhag E, Salomé N, Skibicka KP, Haage D, Bohlooly-Y M, Andersson D, Bjursell M, Perrissoud D, Engel JA, Dickson SL | display-authors = 6 | title = Ghrelin increases intake of rewarding food in rodents | journal = Addiction Biology | volume = 15 | issue = 3 | pages = 304–311 | date = July 2010 | pmid = 20477752 | pmc = 2901520 | doi = 10.1111/j.1369-1600.2010.00216.x }}</ref><ref name = "pmid21309956">{{cite journal | vauthors = Skibicka KP, Hansson C, Egecioglu E, Dickson SL | title = Role of ghrelin in food reward: impact of ghrelin on sucrose self-administration and mesolimbic dopamine and acetylcholine receptor gene expression | journal = Addiction Biology | volume = 17 | issue = 1 | pages = 95–107 | date = January 2012 | pmid = 21309956 | pmc = 3298643 | doi = 10.1111/j.1369-1600.2010.00294.x }}</ref>

Ghrelin has been linked to inducing appetite and feeding behaviors. Circulating ghrelin levels are the highest right before a meal and the lowest right after.<ref name = "pmid11897692">{{cite journal | vauthors = Tolle V, Bassant MH, Zizzari P, Poindessous-Jazat F, Tomasetto C, Epelbaum J, Bluet-Pajot MT | title = Ultradian rhythmicity of ghrelin secretion in relation with GH, feeding behavior, and sleep-wake patterns in rats | journal = Endocrinology | volume = 143 | issue = 4 | pages = 1353–1361 | date = April 2002 | pmid = 11897692 | doi = 10.1210/endo.143.4.8712 | doi-access = free }}</ref><ref name = "pmid15039149">{{cite journal | vauthors = Cummings DE, Frayo RS, Marmonier C, Aubert R, Chapelot D | title = Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 287 | issue = 2 | pages = E297–E304 | date = August 2004 | pmid = 15039149 | doi = 10.1152/ajpendo.00582.2003 | s2cid = 14197143 }}</ref> Injections of ghrelin in both humans and rats have been shown to increase food intake in a dose-dependent manner.<ref name = "pmid11089570">{{cite journal | vauthors = Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR | display-authors = 6 | title = The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion | journal = Endocrinology | volume = 141 | issue = 11 | pages = 4325–4328 | date = November 2000 | pmid = 11089570 | doi = 10.1210/endo.141.11.7873 | doi-access = free }}</ref> So the more ghrelin that is injected the more food that is consumed. However, ghrelin does not increase meal size, only meal number.<ref name = "pmid12941764">{{cite journal | vauthors = Faulconbridge LF, Cummings DE, Kaplan JM, Grill HJ | title = Hyperphagic effects of brainstem ghrelin administration | journal = Diabetes | volume = 52 | issue = 9 | pages = 2260–2265 | date = September 2003 | pmid = 12941764 | doi = 10.2337/diabetes.52.9.2260 | doi-access = free }}</ref> Ghrelin injections also increase an animal's motivation to seek out food, behaviors including increased sniffing, foraging for food, and hoarding food. Body weight is regulated through energy balance, the amount of energy taken in versus the amount of energy expended over an extended period of time. Studies have shown that ghrelin levels are positively correlated with weight. This data suggests that ghrelin functions as an [[adiposity]] signal, a messenger between the body's energy stores and the brain.<ref name = "Schwartz_2000">{{cite journal | vauthors = Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG | title = Central nervous system control of food intake | journal = Nature | volume = 404 | issue = 6778 | pages = 661–671 | date = April 2000 | pmid = 10766253 | doi = 10.1038/35007534 | s2cid = 205005718 | author-link4 = Randy Seeley | author-link1 = Michael Warren Schwartz }}</ref>

==Blood levels==
Blood levels are in the pmol/L or fmol/mL range. Both active and total ghrelin can be measured.<ref name="pmid15863960">{{cite journal | vauthors = Yokota I, Kitamura S, Hosoda H, Kotani Y, Kangawa K | title = Concentration of the n-octanoylated active form of ghrelin in fetal and neonatal circulation | journal = Endocrine Journal | volume = 52 | issue = 2 | pages = 271–276 | date = April 2005 | pmid = 15863960 | doi = 10.1507/endocrj.52.271 | doi-access = free }}</ref>  Circulating ghrelin concentrations rise before eating and fall afterward,<ref name = "pmid11897692"/> more strongly in response to protein and carbohydrate than to lipids.<ref name = "Stengel_Tache_2011" /> The plasma ghrelin-like immunoreactivity concentration measured with a particular [[radioimmunoassay]] in a typical human is 166.0 <u>+</u> 10.1 fmol/mL. Serum ghrelin concentrations tend to increase in age and vary throughout the day, with values peaking while one is asleep.<ref>{{cite journal | vauthors = Ibrahim Abdalla MM | title = Ghrelin - Physiological Functions and Regulation | journal = European Endocrinology | volume = 11 | issue = 2 | pages = 90–95 | date = August 2015 | pmid = 29632576 | pmc = 5819073 | doi = 10.17925/EE.2015.11.02.90 }}</ref>

==Ghrelin receptor==
The ghrelin receptor ''GHS-R1a'' (a splice-variant of the [[growth hormone secretagogue receptor]], with the ''GHS-R1b'' splice being inactive) is involved in mediating a wide variety of biological effects of ghrelin, including: stimulation of growth hormone release, increase in hunger, modulation of glucose and lipid metabolism, regulation of gastrointestinal motility and secretion, protection of neuronal and cardiovascular cells, and regulation of immune function.<ref name="pmid24651458">{{cite journal | vauthors = Yin Y, Li Y, Zhang W | title = The growth hormone secretagogue receptor: its intracellular signaling and regulation | journal = International Journal of Molecular Sciences | volume = 15 | issue = 3 | pages = 4837–4855 | date = March 2014 | pmid = 24651458 | pmc = 3975427 | doi = 10.3390/ijms15034837 | doi-access = free }}</ref> They are present in high density in the hypothalamus and pituitary, on the vagus nerve (on both afferent cell bodies and efferent nerve endings) and throughout the gastrointestinal tract.<ref name = "pmid19896496">{{cite journal | vauthors = Castañeda TR, Tong J, Datta R, Culler M, Tschöp MH | title = Ghrelin in the regulation of body weight and metabolism | journal = Frontiers in Neuroendocrinology | volume = 31 | issue = 1 | pages = 44–60 | date = January 2010 | pmid = 19896496 | doi = 10.1016/j.yfrne.2009.10.008 | s2cid = 23820027 | author-link5 = Matthias H. Tschöp }}</ref><ref name = "pmid17290011">{{cite journal | vauthors = Page AJ, Slattery JA, Milte C, Laker R, O'Donnell T, Dorian C, Brierley SM, Blackshaw LA | display-authors = 6 | title = Ghrelin selectively reduces mechanosensitivity of upper gastrointestinal vagal afferents | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 292 | issue = 5 | pages = G1376–G1384 | date = May 2007 | pmid = 17290011 | doi = 10.1152/ajpgi.00536.2006 | s2cid = 10681559 }}</ref>

==Locations of action==

===Glucose metabolism===
The entire ghrelin system (dAG, AG, GHS-R and GOAT) has a gluco-regulatory action.<ref name="pmid24714083">{{cite journal | vauthors = Heppner KM, Tong J | title = Mechanisms in endocrinology: regulation of glucose metabolism by the ghrelin system: multiple players and multiple actions | journal = European Journal of Endocrinology | volume = 171 | issue = 1 | pages = R21–R32 | date = July 2014 | pmid = 24714083 | doi = 10.1530/EJE-14-0183 | doi-access = free }}</ref>

===Sleep===
Preliminary research indicates that ghrelin participates in the regulation of [[circadian rhythm]]s.<ref name=muller/> A review reported finding strong evidence that sleep restriction affected ghrelin or leptin levels, or energy expenditure.<ref>{{cite journal | vauthors = Zhu B, Shi C, Park CG, Zhao X, Reutrakul S | title = Effects of sleep restriction on metabolism-related parameters in healthy adults: A comprehensive review and meta-analysis of randomized controlled trials | journal = Sleep Medicine Reviews | volume = 45 | pages = 18–30 | date = June 2019 | pmid = 30870662 | doi = 10.1016/j.smrv.2019.02.002 | s2cid = 78091930 }}</ref>

===Reproductive system===
Ghrelin has inhibitory effects on [[gonadotropin-releasing hormone]] (GnRH) secretion. It may cause decreased fertility.<ref name = "pmid24173881">{{cite journal | vauthors = Comninos AN, Jayasena CN, Dhillo WS | title = The relationship between gut and adipose hormones, and reproduction | journal = Human Reproduction Update | volume = 20 | issue = 2 | pages = 153–174 | year = 2014 | pmid = 24173881 | doi = 10.1093/humupd/dmt033 | doi-access = free }}</ref>

===Fetus and neonate===
Ghrelin is produced early by the fetal lung and promotes lung growth.<ref>{{cite journal | vauthors = Santos M, Bastos P, Gonzaga S, Roriz JM, Baptista MJ, Nogueira-Silva C, Melo-Rocha G, Henriques-Coelho T, Roncon-Albuquerque R, Leite-Moreira AF, De Krijger RR, Tibboel D, Rottier R, Correia-Pinto J | display-authors = 6 | title = Ghrelin expression in human and rat fetal lungs and the effect of ghrelin administration in nitrofen-induced congenital diaphragmatic hernia | journal = Pediatric Research | volume = 59 | issue = 4 Pt 1 | pages = 531–537 | date = April 2006 | pmid = 16549524 | doi = 10.1203/01.pdr.0000202748.66359.a9 | doi-access = free | hdl = 1822/67942 | hdl-access = free }}</ref> [[Umbilical cord]] blood levels of ghrelin show a correlation between ghrelin levels and birth weight.<ref name="pmid15863960"/>

=== Cardiovascular system ===
Ghrelin functions as a cardio-protective peptide by being an anti-inflammatory agent, promoting angiogenesis, inhibiting arrhythmia, and improving heart failure.<ref name=":0"/>

=== Immune system ===
Ghrelin has a diverse immunoregulatory role mediating the release of anti-inflammatory cytokines such as IL-4 and 10 along with TGF-β while reducing pro-inflammatory cytokines such as TNF-α, INF-γ, and IL-1β from various immunologically competent cells ''in vitro'' and ''in vivo.'' <ref>{{cite journal | vauthors = Pereira JA, da Silva FC, de Moraes-Vieira PM | title = The Impact of Ghrelin in Metabolic Diseases: An Immune Perspective | journal = Journal of Diabetes Research | volume = 2017 | article-number = 4527980 | date = 2017 | pmid = 29082258 | pmc = 5610818 | doi = 10.1155/2017/4527980 | doi-access = free }}</ref> Additionally, Ghrelin and its endogenous receptor, GHSR1a, along with GOAT are expressed in primary immune tissues such as the spleen and thymus where it has a role in modulating interactions between metabolic state and inflammation, mediating energy balance homeostasis.<ref>{{cite journal | vauthors = Chowen JA, Argente J | title = Ghrelin: A Link Between Energy Homeostasis and the Immune System | journal = Endocrinology | volume = 158 | issue = 7 | pages = 2077–2081 | date = July 2017 | pmid = 28881864 | doi = 10.1210/en.2017-00350 | doi-access = free }}</ref>

=== Stress/ Hypothalamic-pituitary-adrenal (HPA) axis ===
GHSR1A, Ghrelin's endogenous receptor, is expressed within the hypothalamus including the arcuate nucleus, but not in the paraventricular nucleus (PVN) where ghrelin has been found to indirectly affect HPA axis function via neighboring corticotropin releasing hormone (CRH) neurons.<ref>{{cite journal | vauthors = Spencer SJ, Emmerzaal TL, Kozicz T, Andrews ZB | title = Ghrelin's Role in the Hypothalamic-Pituitary-Adrenal Axis Stress Response: Implications for Mood Disorders | journal = Biological Psychiatry | volume = 78 | issue = 1 | pages = 19–27 | date = July 2015 | pmid = 25534754 | doi = 10.1016/j.biopsych.2014.10.021 | s2cid = 38370890 }}</ref> Studies regarding how ghrelin affects cortisol and adrenocorticotropic hormone (ACTH) secretion along with how cortisol and ACTH levels affect ghrelin are inconsistent as different psychological and physical stressors within ''in-vivo'' studies have produced a myriad of results as the underlying mechanisms are still not understood well.<ref>{{cite journal | vauthors = Fritz EM, Singewald N, De Bundel D | title = The Good, the Bad and the Unknown Aspects of Ghrelin in Stress Coping and Stress-Related Psychiatric Disorders | journal = Frontiers in Synaptic Neuroscience | volume = 12 | article-number = 594484 | date = 2020-10-27 | pmid = 33192444 | pmc = 7652849 | doi = 10.3389/fnsyn.2020.594484 | doi-access = free }}</ref>

== Role(s) in disease ==

===Gastric bypass surgery===
[[Gastric bypass surgery]] not only reduces gut capacity for food, but also lowers ghrelin levels compared to both lean people and those who lost weight through dieting.<ref name="muller2">{{cite journal |display-authors=6 |vauthors=Müller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD, Argente J, Batterham RL, Benoit SC, Bowers CY, Broglio F, Casanueva FF, D'Alessio D, Depoortere I, Geliebter A, Ghigo E, Cole PA, Cowley M, Cummings DE, Dagher A, Diano S, Dickson SL, Diéguez C, Granata R, Grill HJ, Grove K, Habegger KM, Heppner K, Heiman ML, Holsen L, Holst B, Inui A, Jansson JO, Kirchner H, Korbonits M, Laferrère B, LeRoux CW, Lopez M, Morin S, Nakazato M, Nass R, Perez-Tilve D, Pfluger PT, Schwartz TW, Seeley RJ, Sleeman M, Sun Y, Sussel L, Tong J, Thorner MO, van der Lely AJ, van der Ploeg LH, Zigman JM, Kojima M, Kangawa K, Smith RG, Horvath T, Tschöp MH |date=June 2015 |title=Ghrelin |journal=Molecular Metabolism |volume=4 |issue=6 |pages=437–460 |doi=10.1016/j.molmet.2015.03.005 |pmc=4443295 |pmid=26042199}}</ref><ref name="pmid120239942">{{cite journal |vauthors=Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ |date=May 2002 |title=Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery |journal=The New England Journal of Medicine |volume=346 |issue=21 |pages=1623–1630 |doi=10.1056/NEJMoa012908 |pmid=12023994|doi-access=free }}</ref> Studies have not clarified whether ghrelin levels return to normal in people who had gastric bypass surgery after weight loss has stabilized.<ref name="pmid128431322">{{cite journal |vauthors=Cummings DE, Shannon MH |date=July 2003 |title=Ghrelin and gastric bypass: is there a hormonal contribution to surgical weight loss? |journal=The Journal of Clinical Endocrinology and Metabolism |volume=88 |issue=7 |pages=2999–3002 |doi=10.1210/jc.2003-030705 |pmid=12843132 |doi-access=free}}</ref> Gastric bypass surgery involving [[vertical-sleeve gastrectomy]] reduces plasma ghrelin levels by about 60% in the long term.<ref name="pmid200948192">{{cite journal |vauthors=Bohdjalian A, Langer FB, Shakeri-Leidenmühler S, Gfrerer L, Ludvik B, Zacherl J, Prager G |date=May 2010 |title=Sleeve gastrectomy as sole and definitive bariatric procedure: 5-year results for weight loss and ghrelin |journal=Obesity Surgery |volume=20 |issue=5 |pages=535–540 |doi=10.1007/s11695-009-0066-6 |pmid=20094819 |s2cid=207303352}}</ref>

===Anorexia and obesity===
Ghrelin levels in the plasma of obese individuals are lower than those in leaner individuals,<ref name="muller2" /><ref name="pmid117886532">{{cite journal |display-authors=6 |vauthors=Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S |date=January 2002 |title=Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion |journal=The Journal of Clinical Endocrinology and Metabolism |volume=87 |issue=1 |pages=240–244 |doi=10.1210/jcem.87.1.8129 |pmid=11788653 |doi-access=free}}</ref> suggesting that ghrelin does not contribute to obesity, except in the cases of [[Prader–Willi syndrome]]-induced obesity, where high ghrelin levels are correlated with increased food intake.<ref name="pmid150709362">{{cite journal |display-authors=6 |vauthors=Goldstone AP, Thomas EL, Brynes AE, Castroman G, Edwards R, Ghatei MA, Frost G, Holland AJ, Grossman AB, Korbonits M, Bloom SR, Bell JD |date=April 2004 |title=Elevated fasting plasma ghrelin in prader-willi syndrome adults is not solely explained by their reduced visceral adiposity and insulin resistance |journal=The Journal of Clinical Endocrinology and Metabolism |volume=89 |issue=4 |pages=1718–1726 |doi=10.1210/jc.2003-031118 |pmid=15070936 |doi-access=free}}</ref><ref name="pmid124663372">{{cite journal |display-authors=6 |vauthors=DelParigi A, Tschöp M, Heiman ML, Salbe AD, Vozarova B, Sell SM, Bunt JC, Tataranni PA |date=December 2002 |title=High circulating ghrelin: a potential cause for hyperphagia and obesity in prader-willi syndrome |journal=The Journal of Clinical Endocrinology and Metabolism |volume=87 |issue=12 |pages=5461–5464 |doi=10.1210/jc.2002-020871 |pmid=12466337 |doi-access=free}}</ref> Those with [[anorexia nervosa]] have high plasma levels of ghrelin<ref name="pmid247316642">{{cite journal |vauthors=Misra M, Klibanski A |date=July 2014 |title=Endocrine consequences of anorexia nervosa |journal=The Lancet. Diabetes & Endocrinology |volume=2 |issue=7 |pages=581–592 |doi=10.1016/S2213-8587(13)70180-3 |pmc=4133106 |pmid=24731664}}</ref> compared to both the constitutionally thin and normal-weight controls.<ref name="pmid125198382">{{cite journal |display-authors=6 |vauthors=Tolle V, Kadem M, Bluet-Pajot MT, Frere D, Foulon C, Bossu C, Dardennes R, Mounier C, Zizzari P, Lang F, Epelbaum J, Estour B |date=January 2003 |title=Balance in ghrelin and leptin plasma levels in anorexia nervosa patients and constitutionally thin women |journal=The Journal of Clinical Endocrinology and Metabolism |volume=88 |issue=1 |pages=109–116 |doi=10.1210/jc.2002-020645 |pmid=12519838 |doi-access=free}}</ref><ref name="pmid174130942">{{cite journal |display-authors=6 |vauthors=Germain N, Galusca B, Le Roux CW, Bossu C, Ghatei MA, Lang F, Bloom SR, Estour B |date=April 2007 |title=Constitutional thinness and lean anorexia nervosa display opposite concentrations of peptide YY, glucagon-like peptide 1, ghrelin, and leptin |journal=The American Journal of Clinical Nutrition |volume=85 |issue=4 |pages=967–971 |doi=10.1093/ajcn/85.4.967 |pmid=17413094 |doi-access=free}}</ref> In healthy individuals, levels of circulating ghrelin increase during the time of day from midnight to dawn. However, a study comparing obese and healthy men found that this nocturnal increase in ghrelin was absent in the obese population, suggesting alterations of circadian patterns in obese men.<ref name="pmid152319972">{{cite journal |vauthors=Yildiz BO, Suchard MA, Wong ML, McCann SM, Licinio J |date=July 2004 |title=Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=101 |issue=28 |pages=10434–10439 |bibcode=2004PNAS..10110434Y |doi=10.1073/pnas.0403465101 |pmc=478601 |pmid=15231997 |doi-access=free}}</ref> Ghrelin levels are high in people with [[cancer]]-induced [[cachexia]].<ref name="pmid157137182">{{cite journal |display-authors=6 |vauthors=Garcia JM, Garcia-Touza M, Hijazi RA, Taffet G, Epner D, Mann D, Smith RG, Cunningham GR, Marcelli M |date=May 2005 |title=Active ghrelin levels and active to total ghrelin ratio in cancer-induced cachexia |journal=The Journal of Clinical Endocrinology and Metabolism |volume=90 |issue=5 |pages=2920–2926 |doi=10.1210/jc.2004-1788 |pmid=15713718 |doi-access=free}}</ref> There is insufficient evidence to conclude either for or against use of ghrelin in managing cachexia associated with cancer.<ref>{{cite journal |vauthors=Khatib MN, Shankar AH, Kirubakaran R, Gaidhane A, Gaidhane S, Simkhada P, Quazi Syed Z |date=February 2018 |title=Ghrelin for the management of cachexia associated with cancer |journal=The Cochrane Database of Systematic Reviews |volume=2 |issue=2 |article-number=CD012229 |doi=10.1002/14651858.cd012229.pub2 |pmc=6491219 |pmid=29489032}}</ref>

=== Effects on cardiovascular system ===
Ghrelin has been theorized to have protective effects on the cardiovascular system. Studies have shown that in mice models of myocardial infarction (MI) with knock-outs of ghrelin, subjects with no endogenous ghrelin production had a significantly increased mortality rate along with worse metrics in terms of cardiac sympathetic activity and systolic function when compared to wild-type subjects.<ref name=":0">{{cite journal | vauthors = Hosoda H | title = Effect of Ghrelin on the Cardiovascular System | journal = Biology | volume = 11 | issue = 8 | page = 1190 | date = August 2022 | pmid = 36009817 | pmc = 9405061 | doi = 10.3390/biology11081190 | doi-access = free }}</ref> with exogenous ghrelin being shown to improve heart function in rodent models of chronic heart failure <ref name=":0" /> and improved ventricular remodeling in post-MI rats.<ref name="Ghrelin and cardiovascular diseases"/>

== See also ==
* [[Hypothalamic–pituitary–somatic axis]]
* [[List of growth hormone secretagogues]]
*[[Leptin]]
*[[Raptin]]

== References ==
{{Reflist}}

== External links ==
{{Wiktionary}}
* {{PDBe-KB2|Q9UBU3|Human Appetite-regulating hormone}}
* {{PDBe-KB2|Q9EQX0|Mouse Appetite-regulating hormone}}

{{Hormones}}
{{Neuropeptides}}
{{Orexigenics}}
{{GH/IGF-1 axis signaling modulators}}

[[Category:Appetite stimulants]]
[[Category:Ghrelin receptor agonists]]
[[Category:Growth hormone secretagogues]]
[[Category:Hormones of the somatotropic axis]]
[[Category:Neuropeptides]]
[[Category:Obesity]]
[[Category:Peptide hormones]]
[[Category:World Anti-Doping Agency prohibited substances]]
[[Category:Pancreatic hormones]]