Biology:Ghrelin

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Short description: Peptide hormone involved in appetite regulation


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


Ghrelin (/ˈɡrɛlɪn/; or lenomorelin, INN) is a hormone primarily produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach,[1][2] and is often called a "hunger hormone" because it increases the drive to eat.[2] Blood levels of ghrelin are highest before meals when hungry, returning to lower levels after mealtimes.[2][3] Ghrelin may help prepare for food intake[2][4] by increasing gastric motility and stimulating the secretion of gastric acid.[2]

Ghrelin activates cells in the anterior pituitary gland and hypothalamic arcuate nucleus,[2][5] including neuropeptide Y neurons that initiate appetite.[2][6] Ghrelin stimulates brain structures having a specific receptor – the growth hormone secretagogue receptor 1A (GHSR-1A).[2][7] Ghrelin also participates in regulation of reward cognition,[8] learning and memory, the sleep-wake cycle, taste sensation, reward behavior, and glucose metabolism.[2][9][10]

History and name

Ghrelin was discovered after the ghrelin receptor (called growth hormone secretagogue type 1A receptor or GHS-R) was determined in 1999.[2] The hormone name is based on its role as a growth hormone-releasing peptide, with reference to the Proto-Indo-European root gʰre-, meaning "to grow".[2]

Gene, transcription products, and structure

Preproghrelin (green and blue) and ghrelin (green)

The GHRL gene produces mRNA which has four exons. 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.[11]

Ghrelin only becomes active when 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.[12] The non-octanoylated form is desacyl ghrelin. It does not activate the GHS-R receptor but does have other effects: cardiac,[13] anti-ghrelin,[14] appetite stimulation,[15] and inhibition of hepatic glucose output.[16] Side-chains other than octanoyl have also been observed: these can also trigger the ghrelin receptor.[17] 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.[18]

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).[19]

Location

Ghrelin cells are found mainly in the stomach[20] and duodenum, but also in the jejunum, lungs, pancreatic islets,[21] gonads, adrenal cortex, placenta, and kidney. It has also been shown that ghrelin is produced locally in the brain.[22] Additionally, research suggests that ghrelin may be produced in the myocardium and have an 'autocrine/ paracrine' like effect within the heart.[23]

Ghrelin cells are also found in oxyntic glands (20% of cells),[24] pyloric glands, and small intestine.

Features

They are ovoid cells with granules.[25] They have gastrin receptors.[26] Some produce nesfatin-1.[27] 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.[28]

Function and mechanism of action

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 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 mTOR/S6K1 pathway mediating the interaction among ghrelin, nesfatin and endocannabinoid gastric systems,[29] and both afferent and efferent vagal signals.

Ghrelin and synthetic ghrelin mimetics (growth hormone secretagogues) increase body weight and fat mass[30][31][32] by triggering receptors in the arcuate nucleus[5] that include neuropeptide Y (NPY) and agouti-related protein (AgRP) neurons.[33][6] Ghrelin-responsiveness of these neurons is both leptin- and insulin-sensitive.[34] Ghrelin reduces the sensitivity of gastric vagal afferents, so they are less sensitive to gastric distension.[35]

In addition to its function in energy homeostasis, ghrelin also activates the cholinergic–dopaminergic reward link in inputs to the ventral tegmental area and in the mesolimbic pathway,[36] a circuit that communicates the hedonic and reinforcing aspects of natural rewards,[9] such as food and addictive drugs such as ethanol.[34][37][38] Ghrelin receptors are located on neurons in this circuit.[9][8] Hypothalamic ghrelin signalling is required for reward from alcohol[39] and palatable/rewarding foods.[40][41]

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.[42][43] Injections of ghrelin in both humans and rats have been shown to increase food intake in a dose-dependent manner.[44] So the more ghrelin that is injected the more food that is consumed. However, ghrelin does not increase meal size, only meal number.[45] 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.[4]

Blood levels

Blood levels are in the pmol/L or fmol/mL range. Both active and total ghrelin can be measured.[46] Circulating ghrelin concentrations rise before eating and fall afterward,[42] more strongly in response to protein and carbohydrate than to lipids.[18] The plasma ghrelin-like immunoreactivity concentration measured with a particular radioimmunoassay in a typical human is 166.0 + 10.1 fmol/mL. Serum ghrelin concentrations tend to increase in age and vary throughout the day, with values peaking while one is asleep.[47]

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.[48] 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.[12][35]

Locations of action

Glucose metabolism

The entire ghrelin system (dAG, AG, GHS-R and GOAT) has a gluco-regulatory action.[49]

Sleep

Preliminary research indicates that ghrelin participates in the regulation of circadian rhythms.[2] A review reported finding strong evidence that sleep restriction affected ghrelin or leptin levels, or energy expenditure.[50]

Reproductive system

Ghrelin has inhibitory effects on gonadotropin-releasing hormone (GnRH) secretion. It may cause decreased fertility.[51]

Fetus and neonate

Ghrelin is produced early by the fetal lung and promotes lung growth.[52] Umbilical cord blood levels of ghrelin show a correlation between ghrelin levels and birth weight.[46]

Cardiovascular system

Ghrelin functions as a cardio-protective peptide by being an anti-inflammatory agent, promoting angiogenesis, inhibiting arrhythmia, and improving heart failure.[53]

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. [54] Additionally, Ghrelin and it's 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.[55]

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.[56] 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.[57]

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.[58][59] Studies have not clarified whether ghrelin levels return to normal in people who had gastric bypass surgery after weight loss has stabilized.[60] Gastric bypass surgery involving vertical-sleeve gastrectomy reduces plasma ghrelin levels by about 60% in the long term.[61]

Anorexia and obesity

Ghrelin levels in the plasma of obese individuals are lower than those in leaner individuals,[58][62] 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.[63][64] Those with anorexia nervosa have high plasma levels of ghrelin[65] compared to both the constitutionally thin and normal-weight controls.[66][67] The level of ghrelin increases during the time of day from midnight to dawn in thinner people, which suggests there is a flaw in the circadian rhythm of obese individuals.[68] Ghrelin levels are high in people with cancer-induced cachexia.[69] There is insufficient evidence to conclude either for or against use of ghrelin in managing cachexia associated with cancer.[70]

Possible Cardiovascular Therapeutic Potential

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.[53] with exogenous ghrelin being shown to improve heart function in rodent models of chronic heart failure [53] and improved ventricular remodeling in post-MI rats.[23]

See also

  • Hypothalamic–pituitary–somatic axis
  • List of growth hormone secretagogues
  • Leptin

References

  1. ↑ "Ghrelin is a growth-hormone-releasing acylated peptide from stomach". Nature 402 (6762): 656–660. December 1999. doi:10.1038/45230. PMID 10604470. Bibcode: 1999Natur.402..656K. 
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 "Ghrelin". Molecular Metabolism 4 (6): 437–460. June 2015. doi:10.1016/j.molmet.2015.03.005. PMID 26042199. 
  3. ↑ "A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans". Diabetes 50 (8): 1714–1719. August 2001. doi:10.2337/diabetes.50.8.1714. PMID 11473029. 
  4. ↑ 4.0 4.1 "Central nervous system control of food intake". Nature 404 (6778): 661–671. April 2000. doi:10.1038/35007534. PMID 10766253. 
  5. ↑ 5.0 5.1 "Systemic administration of growth hormone-releasing peptide activates hypothalamic arcuate neurons". Neuroscience 53 (2): 303–306. March 1993. doi:10.1016/0306-4522(93)90197-n. PMID 8492908. 
  6. ↑ 6.0 6.1 "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". Endocrinology 138 (2): 771–777. February 1997. doi:10.1210/endo.138.2.4907. PMID 9003014. 
  7. ↑ "A receptor in pituitary and hypothalamus that functions in growth hormone release". Science 273 (5277): 974–977. August 1996. doi:10.1126/science.273.5277.974. PMID 8688086. Bibcode: 1996Sci...273..974H. 
  8. ↑ 8.0 8.1 "Neural and Neuroendocrine Control of the Internal Milieu". Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (3rd ed.). New York: McGraw-Hill Medical. 2015. pp. 245–267. ISBN 9780071827690. 
  9. ↑ Le Moal M (2002). "Mesocorticolimbic Dopaminergic Neurons". Neuropsychopharmacology : the fifth generation of progress : an official publication of the American College of Neuropsychopharmacology (5th ed.). Philadelphia, Pa.: Lippincott Williams & Wilkins. ISBN 978-0781728379. http://www.acnp.org/g4/gn401000025/ch025.html. Retrieved 21 May 2014. 
  10. ↑ "Ghrelin gene-related peptides: multifunctional endocrine / autocrine modulators in health and disease". Clinical and Experimental Pharmacology & Physiology 37 (1): 125–131. January 2010. doi:10.1111/j.1440-1681.2009.05241.x. PMID 19566830. 
  11. ↑ 12.0 12.1 "Ghrelin in the regulation of body weight and metabolism". Frontiers in Neuroendocrinology 31 (1): 44–60. January 2010. doi:10.1016/j.yfrne.2009.10.008. PMID 19896496. 
  12. ↑ "Cardiac effects of ghrelin and its endogenous derivatives des-octanoyl ghrelin and des-Gln14-ghrelin". European Journal of Pharmacology 476 (1–2): 87–95. August 2003. doi:10.1016/S0014-2999(03)02083-1. PMID 12969753. 
  13. ↑ "Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans". The Journal of Clinical Endocrinology and Metabolism 89 (6): 3062–3065. June 2004. doi:10.1210/jc.2003-031964. PMID 15181099. 
  14. ↑ "Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor". Endocrinology 147 (5): 2306–2314. May 2006. doi:10.1210/en.2005-1357. PMID 16484324. 
  15. ↑ "Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes". The Journal of Clinical Endocrinology and Metabolism 90 (2): 1055–1060. February 2005. doi:10.1210/jc.2004-1069. PMID 15536157. 
  16. ↑ "Ghrelin--a hormone with multiple functions". Frontiers in Neuroendocrinology 25 (1): 27–68. April 2004. doi:10.1016/j.yfrne.2004.03.002. PMID 15183037. 
  17. ↑ 18.0 18.1 "Interaction between gastric and upper small intestinal hormones in the regulation of hunger and satiety: ghrelin and cholecystokinin take the central stage". Current Protein & Peptide Science 12 (4): 293–304. June 2011. doi:10.2174/138920311795906673. PMID 21428875. 
  18. ↑ "Mice lacking ghrelin receptors resist the development of diet-induced obesity". The Journal of Clinical Investigation 115 (12): 3564–3572. December 2005. doi:10.1172/JCI26002. PMID 16322794. 
  19. ↑ "Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans". The Journal of Clinical Endocrinology and Metabolism 86 (10): 4753–4758. October 2001. doi:10.1210/jcem.86.10.7885. PMID 11600536. 
  20. ↑ "Pancreas islets in metabolic signaling--focus on the beta-cell". Frontiers in Bioscience 13 (13): 7156–7171. May 2008. doi:10.2741/3218. PMID 18508724. 
  21. ↑ "Ghrelin in central neurons". Current Neuropharmacology 7 (1): 37–49. March 2009. doi:10.2174/157015909787602779. PMID 19721816. 
  22. ↑ 23.0 23.1 "Ghrelin and cardiovascular diseases". Current Cardiology Reviews 6 (1): 62–70. February 2010. doi:10.2174/157340310790231662. PMID 21286280. 
  23. ↑ "Endocrine cells in the human oxyntic mucosa. A histochemical study". Scandinavian Journal of Gastroenterology 23 (9): 1089–1099. November 1988. doi:10.3109/00365528809090174. PMID 2470131. 
  24. ↑ "Morphology and function of the entero-endocrine cells". Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et Metabolisme 11 (11): 589–606. November 1979. doi:10.1055/s-0028-1092785. PMID 94030. 
  25. ↑ "Synergistic action of gastrin and ghrelin on gastric acid secretion in rats". Biochemical and Biophysical Research Communications 374 (1): 60–63. September 2008. doi:10.1016/j.bbrc.2008.06.114. PMID 18611393. 
  26. ↑ "Novel insight in distribution of nesfatin-1 and phospho-mTOR in the arcuate nucleus of the hypothalamus of rats". Peptides 31 (2): 257–262. February 2010. doi:10.1016/j.peptides.2009.11.024. PMID 19961888. 
  27. ↑ "Ghrelin expression in the mouse pancreas defines a unique multipotent progenitor population". PLOS ONE 7 (12): e52026. 2012. doi:10.1371/journal.pone.0052026. PMID 23251675. Bibcode: 2012PLoSO...752026A. 
  28. ↑ "The Brain-Stomach Connection". How Gut and Brain Control Metabolism. Frontiers of Hormone Research. 42. Basel: Karger. 2014. pp. 83–92. doi:10.1159/000358316. ISBN 978-3-318-02638-2. 
  29. ↑ "Growth hormone (GH)-independent stimulation of adiposity by GH secretagogues". Biochemical and Biophysical Research Communications 280 (1): 132–138. January 2001. doi:10.1006/bbrc.2000.4065. PMID 11162489. 
  30. ↑ "Ghrelin induces adiposity in rodents". Nature 407 (6806): 908–913. October 2000. doi:10.1038/35038090. PMID 11057670. Bibcode: 2000Natur.407..908T. 
  31. ↑ "Enhanced responsiveness of Ghsr Q343X rats to ghrelin results in enhanced adiposity without increased appetite". Science Signaling 9 (424): ra39. April 2016. doi:10.1126/scisignal.aae0374. PMID 27095593. https://www.hal.inserm.fr/inserm-01463897/file/aae0374_ArticleContent_v13_proofs_FOR%20HAL.pdf. 
  32. ↑ "Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein". Endocrinology 145 (6): 2607–2612. June 2004. doi:10.1210/en.2003-1596. PMID 14962995. 
  33. ↑ 34.0 34.1 "The rat arcuate nucleus integrates peripheral signals provided by leptin, insulin, and a ghrelin mimetic". Diabetes 51 (12): 3412–3419. December 2002. doi:10.2337/diabetes.51.12.3412. PMID 12453894. 
  34. ↑ 35.0 35.1 "Ghrelin selectively reduces mechanosensitivity of upper gastrointestinal vagal afferents". American Journal of Physiology. Gastrointestinal and Liver Physiology 292 (5): G1376–G1384. May 2007. doi:10.1152/ajpgi.00536.2006. PMID 17290011. 
  35. ↑ "Ghrelin induces feeding in the mesolimbic reward pathway between the ventral tegmental area and the nucleus accumbens". Peptides 26 (11): 2274–2279. November 2005. doi:10.1016/j.peptides.2005.04.025. PMID 16137788. 
  36. ↑ "Ghrelin stimulates locomotor activity and accumbal dopamine-overflow via central cholinergic systems in mice: implications for its involvement in brain reward". Addiction Biology 11 (1): 45–54. March 2006. doi:10.1111/j.1369-1600.2006.00002.x. PMID 16759336. 
  37. ↑ "Ghrelin administration into tegmental areas stimulates locomotor activity and increases extracellular concentration of dopamine in the nucleus accumbens". Addiction Biology 12 (1): 6–16. March 2007. doi:10.1111/j.1369-1600.2006.00041.x. PMID 17407492. 
  38. ↑ "Requirement of central ghrelin signaling for alcohol reward". Proceedings of the National Academy of Sciences of the United States of America 106 (27): 11318–11323. July 2009. doi:10.1073/pnas.0812809106. PMID 19564604. Bibcode: 2009PNAS..10611318J. 
  39. ↑ "Ghrelin increases intake of rewarding food in rodents". Addiction Biology 15 (3): 304–311. July 2010. doi:10.1111/j.1369-1600.2010.00216.x. PMID 20477752. 
  40. ↑ "Role of ghrelin in food reward: impact of ghrelin on sucrose self-administration and mesolimbic dopamine and acetylcholine receptor gene expression". Addiction Biology 17 (1): 95–107. January 2012. doi:10.1111/j.1369-1600.2010.00294.x. PMID 21309956. 
  41. ↑ 42.0 42.1 "Ultradian rhythmicity of ghrelin secretion in relation with GH, feeding behavior, and sleep-wake patterns in rats". Endocrinology 143 (4): 1353–1361. April 2002. doi:10.1210/endo.143.4.8712. PMID 11897692. 
  42. ↑ "Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues". American Journal of Physiology. Endocrinology and Metabolism 287 (2): E297–E304. August 2004. doi:10.1152/ajpendo.00582.2003. PMID 15039149. 
  43. ↑ "The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion". Endocrinology 141 (11): 4325–4328. November 2000. doi:10.1210/endo.141.11.7873. PMID 11089570. 
  44. ↑ "Hyperphagic effects of brainstem ghrelin administration". Diabetes 52 (9): 2260–2265. September 2003. doi:10.2337/diabetes.52.9.2260. PMID 12941764. 
  45. ↑ 46.0 46.1 "Concentration of the n-octanoylated active form of ghrelin in fetal and neonatal circulation". Endocrine Journal 52 (2): 271–276. April 2005. doi:10.1507/endocrj.52.271. PMID 15863960. 
  46. ↑ "Ghrelin - Physiological Functions and Regulation". European Endocrinology 11 (2): 90–95. August 2015. doi:10.17925/EE.2015.11.02.90. PMID 29632576. 
  47. ↑ "The growth hormone secretagogue receptor: its intracellular signaling and regulation". International Journal of Molecular Sciences 15 (3): 4837–4855. March 2014. doi:10.3390/ijms15034837. PMID 24651458. 
  48. ↑ "Mechanisms in endocrinology: regulation of glucose metabolism by the ghrelin system: multiple players and multiple actions". European Journal of Endocrinology 171 (1): R21–R32. July 2014. doi:10.1530/EJE-14-0183. PMID 24714083. 
  49. ↑ "Effects of sleep restriction on metabolism-related parameters in healthy adults: A comprehensive review and meta-analysis of randomized controlled trials". Sleep Medicine Reviews 45: 18–30. June 2019. doi:10.1016/j.smrv.2019.02.002. PMID 30870662. 
  50. ↑ "The relationship between gut and adipose hormones, and reproduction". Human Reproduction Update 20 (2): 153–174. 2014. doi:10.1093/humupd/dmt033. PMID 24173881. 
  51. ↑ "Ghrelin expression in human and rat fetal lungs and the effect of ghrelin administration in nitrofen-induced congenital diaphragmatic hernia". Pediatric Research 59 (4 Pt 1): 531–537. April 2006. doi:10.1203/01.pdr.0000202748.66359.a9. PMID 16549524. 
  52. ↑ 53.0 53.1 53.2 "Effect of Ghrelin on the Cardiovascular System". Biology 11 (8): 1190. August 2022. doi:10.3390/biology11081190. PMID 36009817. 
  53. ↑ "The Impact of Ghrelin in Metabolic Diseases: An Immune Perspective". Journal of Diabetes Research 2017: 4527980. 2017. doi:10.1155/2017/4527980. PMID 29082258. 
  54. ↑ "Ghrelin: A Link Between Energy Homeostasis and the Immune System". Endocrinology 158 (7): 2077–2081. July 2017. doi:10.1210/en.2017-00350. PMID 28881864. 
  55. ↑ "Ghrelin's Role in the Hypothalamic-Pituitary-Adrenal Axis Stress Response: Implications for Mood Disorders". Biological Psychiatry 78 (1): 19–27. July 2015. doi:10.1016/j.biopsych.2014.10.021. PMID 25534754. 
  56. ↑ "The Good, the Bad and the Unknown Aspects of Ghrelin in Stress Coping and Stress-Related Psychiatric Disorders". Frontiers in Synaptic Neuroscience 12: 594484. 2020-10-27. doi:10.3389/fnsyn.2020.594484. PMID 33192444. 
  57. ↑ 58.0 58.1 "Ghrelin". Molecular Metabolism 4 (6): 437–460. June 2015. doi:10.1016/j.molmet.2015.03.005. PMID 26042199. 
  58. ↑ "Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery". The New England Journal of Medicine 346 (21): 1623–1630. May 2002. doi:10.1056/NEJMoa012908. PMID 12023994. 
  59. ↑ "Ghrelin and gastric bypass: is there a hormonal contribution to surgical weight loss?". The Journal of Clinical Endocrinology and Metabolism 88 (7): 2999–3002. July 2003. doi:10.1210/jc.2003-030705. PMID 12843132. 
  60. ↑ "Sleeve gastrectomy as sole and definitive bariatric procedure: 5-year results for weight loss and ghrelin". Obesity Surgery 20 (5): 535–540. May 2010. doi:10.1007/s11695-009-0066-6. PMID 20094819. 
  61. ↑ "Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion". The Journal of Clinical Endocrinology and Metabolism 87 (1): 240–244. January 2002. doi:10.1210/jcem.87.1.8129. PMID 11788653. 
  62. ↑ "Elevated fasting plasma ghrelin in prader-willi syndrome adults is not solely explained by their reduced visceral adiposity and insulin resistance". The Journal of Clinical Endocrinology and Metabolism 89 (4): 1718–1726. April 2004. doi:10.1210/jc.2003-031118. PMID 15070936. 
  63. ↑ "High circulating ghrelin: a potential cause for hyperphagia and obesity in prader-willi syndrome". The Journal of Clinical Endocrinology and Metabolism 87 (12): 5461–5464. December 2002. doi:10.1210/jc.2002-020871. PMID 12466337. 
  64. ↑ "Endocrine consequences of anorexia nervosa". The Lancet. Diabetes & Endocrinology 2 (7): 581–592. July 2014. doi:10.1016/S2213-8587(13)70180-3. PMID 24731664. 
  65. ↑ "Balance in ghrelin and leptin plasma levels in anorexia nervosa patients and constitutionally thin women". The Journal of Clinical Endocrinology and Metabolism 88 (1): 109–116. January 2003. doi:10.1210/jc.2002-020645. PMID 12519838. 
  66. ↑ "Constitutional thinness and lean anorexia nervosa display opposite concentrations of peptide YY, glucagon-like peptide 1, ghrelin, and leptin". The American Journal of Clinical Nutrition 85 (4): 967–971. April 2007. doi:10.1093/ajcn/85.4.967. PMID 17413094. 
  67. ↑ "Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity". Proceedings of the National Academy of Sciences of the United States of America 101 (28): 10434–10439. July 2004. doi:10.1073/pnas.0403465101. PMID 15231997. Bibcode: 2004PNAS..10110434Y. 
  68. ↑ "Active ghrelin levels and active to total ghrelin ratio in cancer-induced cachexia". The Journal of Clinical Endocrinology and Metabolism 90 (5): 2920–2926. May 2005. doi:10.1210/jc.2004-1788. PMID 15713718. 
  69. ↑ "Ghrelin for the management of cachexia associated with cancer". The Cochrane Database of Systematic Reviews 2 (2): CD012229. February 2018. doi:10.1002/14651858.cd012229.pub2. PMID 29489032. 

External links

  • Overview of all the structural information available in the PDB for UniProt: Q9UBU3 (Human Appetite-regulating hormone) at the PDBe-KB.
  • Overview of all the structural information available in the PDB for UniProt: Q9EQX0 (Mouse Appetite-regulating hormone) at the PDBe-KB.



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