• Main page
• About the journal
• Editorial board
• Subscription
• Information for contributors
• Editorial and Peer Review
• Issues archive
• Authors
• Articles
  • By alphabet
  • By category
• Blogs and comments

The journal is included into The list of leading scientific periodicals.

The journal is included into VINITI database and is registered in Electronic scientific library.

The journal is indexed by SCOPUS, Ulrich's International Periodicals Directory.

EBSCO

https://doi.org/10.14300/mnnc.2023.18099

The role of ghrelin in normal and pathological conditions

[Reviews]
Vladimir Alexandrovich Shcherbak; Natalia Arkadyevna Ishchenko; Natalia Mikhailovna Shcherbak; Tatiana Aksenova;

The purpose of the scientific review is to summarize the information available in the literature (2017–2023) on the role of ghrelin (G) in normal and pathological conditions. The databases PubMED, RSCI were used. 28536 publications were found for search words. G plays an important role in the modulation of carbohydrate and lipid metabolism, its effects appear in the central nervous system, pancreas and adipose tissue. The first discovered effect of G was to stimulate the release of growth hormone from the anterior pituitary gland. Later, its influence on carbohydrate and fat metabolism was revealed, as well as its anti-inflammatory effect. The level of G increases on the eve of a meal, and after saturation it decreases. G is an antagonist of leptin produced by adipose tissue. The level of G increases in eating disorders and Prader – Willi syndrome, and decreases in obesity. Physician’s attention to the level of G and its receptor can bring therapeutic benefits to people with obesity and impaired carbohydrate and lipid metabolism.

Download

References:
1. Lv Y., Liang T., Wang G., Li Z. Ghrelin, a gastrointestinal hormone, regulates energy balance and lipid metabolism. Bioscience Reports. 2018;38(5):BSR20181061. https://doi.org/10.1042/bsr20181061
2. Akalu Y., Molla M. D., Dessie G, Ayelign B. Physiological Effect of Ghrelin on Body Systems. International Journal of Endocrinology. 2020;2020:1385138. https://doi.org/10.1155/2020/7828392
3. 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. https://doi.org/10.1038/45230
4. Sato T., Ida T., Shiimura Y., Matsui K., Oishi K., Kojima M. Insights Into the Regulation of Offspring Growth by Maternally Derived Ghrelin. Frontiers in Endocrinology (Lausanne). 2022;13:852636. https://doi.org/10.3389/fendo.2022.852636
5. Dimas A., Politi A., Papaioannou G., Barber T. M., Weickert M. O. [et al.]. The Gestational Effects of Maternal Appetite Axis Molecules on Fetal Growth, Metabolism and Long-Term Metabolic Health: A Systematic Review. International Journal of Molecular Sciences. 2022;23(2):695. https://doi.org/10.3390/ijms23020695
6. Jiao Z. T., Luo Q. Molecular Mechanisms and Health Benefits of Ghrelin: A Narrative Review. Nutrients. 2022;14(19):4191. https://doi.org/10.3390/nu14194191
7. Shankar K., Gupta D., Mani B. K., Findley B. G., OsborneLawrence S. [et al.]. Ghrelin Protects Against InsulinInduced Hypoglycemia in a Mouse Model of Type 1 Diabetes Mellitus. Frontiers in Endocrinology (Lausanne). 2020;11:606. https://doi.org/10.3389/fendo.2020.00606
8. Bouillon-Minois J. B., Trousselard M., Thivel D., Gordon B. A., Schmidt J. [et al.]. Ghrelin as a Biomarker of Stress: A Systematic Review and Meta-Analysis. Nutrients. 2021;13(3):784. https://doi.org/10.3390/nu13030784
9. Micarelli A., Vezzoli A., Malacrida S., Micarelli B., Misici I. [et al.]. Taste Function in Adult Humans from Lean Condition to Stage II Obesity: Interactions with Biochemical Regulators, Dietary Habits, and Clinical Aspects. Nutrients. 2023;15(5):1114. https://doi.org/10.3390/nu15051114
10. Al Massadi O., López M., Tschöp M., Diéguez C., Nogueiras R. Current Understanding of the Hypothalamic Ghrelin Pathways Inducing Appetite and Adiposity. Trends in Neuroscience. 2017;40(3):167-180. https://doi.org/10.1016/j.tins.2016.12.003
11. Tamboli R. A., Antoun J., Sidani R. M., Clements A., Harmata E. E. [et al.]. Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans. Diabetes, Obesity and Metabolism. 2017;19(9):1267-1275. https://doi.org/10.1111/dom.12952
12. de Guia R. M., Hassing A. S., Skov L. J., Ratner C., Plucińska K. [et al.]. Fasting- and ghrelin-induced food intake is regulated by NAMPT in the hypothalamus. Acta Physiologica (Oxford). 2020 ;228(4):e13437. https://doi.org/10.1111/apha.13437
13. Dagher-Hamalian C., Stephan J., Zeeni N., Harhous Z., Shebaby W. N. [et al.]. Ghrelin-induced multi-organ damage in mice fed obesogenic diet. Inflammation Research. 2020;69(10):1019-1026. https://doi.org/10.1007/s00011-020-01383-5
14. Moura-Assis A., Friedman J. M., Velloso L. A. Gut-to-brain signals in feeding control. American Journal of Physiology Endocrinology and Metabolism. 2021;320(2):E326-E332. https://doi.org/10.1152/ajpendo.00388.2020
15. Gonzalez I. E., Ramirez-Matias J., Lu C., Pan W., Zhu A. [et al.]. Paraventricular Calcitonin Receptor-Expressing Neurons Modulate Energy Homeostasis in Male Mice. Endocrinology. 2021;162(6):bqab072. https://doi.org/10.1210/endocr/bqab072
16. Al Massadi O., Nogueiras R., Dieguez C., Girault J. A. Ghrelin and food reward. Neuropharmacology. 2019;148:131-138. https://doi.org/10.1016/j.neuropharm.2019.01.001
17. Han J., Liang X., Guo Y., Wu X., Li Z., Hong T. Agouti-related protein as the glucose signaling sensor in the central melanocortin circuits in regulating fish food intake. Frontiers in Endocrinology (Lausanne). 2022;13:1010472. https://doi.org/10.3389/fendo.2022.1010472
18. Kempf E., Landgraf K., Stein R., Hanschkow M., Hilbert A. [et al.]. Aberrant expression of agouti signaling protein (ASIP) as a cause of monogenic severe childhood obesity. Nature Metabolism. 2022;4(12):1697-1712. https://doi.org/10.1038/s42255-022-00703-9
19. Panigrahi S. K., Toedesbusch C. D., McLeland J. S., Lucey B. P., Wardlaw S. L. Diurnal Patterns for Cortisol, Cortisone and Agouti-Related Protein in Human Cerebrospinal Fluid and Blood. Journal of Clinical Endocrinology and Metabolism. 2020;105(4):e1584-e1592. https://doi.org/10.1210/clinem/dgz274
20. Lass J., Nielsen M. L., Bjørnvad C. R., Vitger A. D, Cremer S. E. Analytical performance of canine acylated and unacylated ghrelin enzyme-linked immunosorbent assays. Veterinary Clinical Pathology. 2019;48(4):748-753. https://doi.org/10.1111/vcp.12801
21. Wang Y., Wu Q., Zhou Q., Chen Y., Lei X. [et al.]. Circulating acyl and des-acyl ghrelin levels in obese adults: a systematic review and meta-analysis. Scientific Reports. 2022;12(1):2679. https://doi.org/10.1038/s41598-022-06636-3
22. Isokawa M. Ghrelin-O-acyltransferase (GOAT) acrylates ghrelin in the hippocampus. Vitamins and Hormones. 2022;118:369-392. https://doi.org/10.1016/bs.vh.2021.11.008
23. Hougland J. L. Ghrelin octanoylation by ghrelin O-acyltransferase: Unique protein biochemistry underlying metabolic signaling. Biochemical Society Transaction. 2019;47(1):169-178. https://doi.org/10.1042/bst20180436
24. Micioni Di Bonaventura E., Botticelli L., Del Bello F., Giorgioni G. [et al.]. Assessing the role of ghrelin and the enzyme ghrelin O-acyltransferase (GOAT) system in food reward, food motivation, and binge eating behavior. Pharmacological Research. 2021;172:105847. https://doi.org/10.1016/j.phrs.2021.105847
25. Liang Y., Yin W., Yin Y., Zhang W. Ghrelin Based Therapy of Metabolic Diseases. Current Medical Chemistry. 2021;28(13):2565-2576. https://doi.org/10.2174/0929867327666200615152804
26. Moose J. E., Leets K. A., Mate N. A., Chisholm J. D., Hougland J. L. An overview of ghrelin O-acyltransferase inhibitors: a literature and patent review for 2010-2019. Expert Opinion in Therapeutically Patents. 2020;30(8):581-593. https://doi.org/10.1080/13543776.2020.1776263
27. Hosseini F. S., Ghassempour A., Amanlou M. Discovery of novel inhibitors of ghrelin O-acyltransferase enzyme: an insilico approach. Research in Pharmaceutical Science. 2022;17(5):540-557. https://doi.org/10.4103/1735-5362.355212
28. Smith A., Woodside B., Abizaid A. Ghrelin and the Control of Energy Balance in Females. Frontiers in Endocrinology (Lausanne). 2022;13:904754. https://doi.org/10.3389/fendo.2022.904754
29. Espinoza García A. S., Martínez Moreno A. G., Reyes Castillo Z. The role of ghrelin and leptin in feeding behavior: Genetic and molecular evidence. Endocrinololia Diabetes y Nutrition (English Edition). 2021;68(9):654-663. https://doi.org/10.1016/j.endien.2020.10.009
30. Davis J. Hunger, ghrelin and the gut. Brain Research. 2018;1693(Pt B):154-158. https://doi.org/10.1016/j.brainres.2018.01.024
31. Deschaine S. L., Leggio L. From «Hunger Hormone» to «It’s Complicated»: Ghrelin Beyond Feeding Control. Physiology (Bethesda). 2022;37(1):5-15. https://doi.org/10.1152/physiol.00024.2021
32. Kitazawa T., Kaiya H. Regulation of Gastrointestinal Motility by Motilin and Ghrelin in Vertebrates. Frontiers in Endocrinology (Lausanne). 2019;10:278. https://doi.org/10.3389/fendo.2019.00278
33. Lin Y., Liang Z., He L., Yang M., Liu D. [et al.]. Gut ghrelin regulates hepatic glucose production and insulin signaling via a gut-brain-liver pathway. Cell Communication and Signaling. 2019;17(1):8. https://doi.org/10.1186/s12964-019-0321-y
34. Watts A. G., Kanoski S. E., Sanchez-Watts G., Langhans W. The physiological control of eating: signals, neurons, and networks. Physiological Reviews. 2022;102(2):689-813. https://doi.org/10.1152/physrev.00028.2020
35. Gupta D., Dowsett G. K. C., Mani B. K, Shankar K., Osborne-Lawrence S. [et al.]. High Coexpression of the Ghrelin and LEAP2 Receptor GHSR With Pancreatic Polypeptide in Mouse and Human Islets. Endocrinology. 2021;162(10):bqab148. https://doi.org/10.1210/endocr/bqab148
36. Abizaid A. Stress and obesity: The ghrelin connection. Journal of Neuroendocrinology. 2019;31(7):e12693. https://doi.org/10.1111/jne.12693
37. Gupta D., Ogden S. B., Shankar K., Varshney S., Zigman J. M. «A LEAP 2 conclusions? Targeting the ghrelin system to treat obesity and diabetes». Molecular Metabolism. 2021;46:101128. https://doi.org/10.1016/j.molmet.2020.101128
38. Tauber M., Coupaye M., Diene G., Molinas C., Valette M., Beauloye V. Prader-Willi syndrome: A model for understanding the ghrelin system. Journal of Neuroendocrinology. 2019;31(7):e12728. https://doi.org/10.1111/jne.12728
39. Erhardt É., Molnár D. Prader-Willi Syndrome: Possibilities of Weight Gain Prevention and Treatment. Nutrients. 2022;14(9):1950. https://doi.org/10.3390/nu14091950
40. Ozmen S., Şeker A., Demirci E. Ghrelin and leptin levels in children with anxiety disorders. Journal of Pediatric Endocrinology and Metabolism. 2019;32(10):1043-1047. https://doi.org/10.1515/jpem-2019-0229
41. Goyal R. K., Guo Y., Mashimo H. Advances in the physiology of gastric emptying. Neurogastroenterology and Motility. 2019;31(4):e13546. https://doi.org/10.1111/nmo.13546
42. Lugilde J., Casado S., Beiroa D., Cuñarro J., Garcia-Lavandeira M. [et al.]. LEAP-2 Counteracts Ghrelin-Induced Food Intake in a Nutrient, Growth Hormone and Age Independent Manner. Cells. 2022;11(3):324. https://doi.org/10.3390/cells11030324
43. Isakova D. N., Petrov I. M., Evgen’eva E. A., Kurmangulov A. A., Troshina I. A., Vasilkova T. N. Eating disorders: predictors of development in disorders of carbohydrate metabolism. Zabaykalsky meditsinsky vestnik. – Transbaikal Medical Bulletin. 2023;1:137-148. (In Russ.). https://doi.org/10.52485/19986173_2023_1_137
44. Bolotova N. V., Kurdiyan M. S., Filina N. Yu. Neuroendocrine mechanisms of regulation of eating behavior (review). Saratovsky nauchno-meditsinsky zhurnal. – Saratov Scientific Medical Journal. 2020;16(3):707-713. (In Russ.)
45. Davies J. S. Ghrelin mediated hippocampal neurogenesis. Vitamins and Hormones. 2022;118:337-367. https://doi.org/10.1016/bs.vh.2021.12.003
46. Smith A., Woodside B., Abizaid A. Ghrelin and the Control of Energy Balance in Females. Frontiers in Endocrinology (Lausanne). 2022;13:904754. https://doi.org/10.3389/fendo.2022.904754
47. Tamura H., Kamegai J., Shimizu T., Ishii S., Sugihara H., Oikawa S. Ghrelin stimulates GH but not food intake in arcuate nucleus ablated rats. Endocrinology. 2002;143(9):3268-75. https://doi.org/10.1210/en.2002-220268
48. van Loenen M. R., Geenen B., Arnoldussen I. A. C., Kiliaan A. J. Ghrelin as a prominent endocrine factor in stress-induced obesity. Nutritional Neuroscience. 2022;25(7):1413-1424. https://doi.org/10.1080/1028415x.2020.1863740
49. Quinino R. M. E. Ghrelin and Its Role as a Marker of Obesity Severity. Obesity Surgery. 2023;33(4):1274-1275. https://doi.org/10.1007/s11695-023-06483-9
50. Nagi K., Habib A. M. Biased signaling: A viable strategy to drug ghrelin receptors for the treatment of obesity. Cellular Signaling. 2021;83:109976. https://doi.org/10.1016/j.cellsig.2021.109976
51. Abizaid A., Hougland J. L. Ghrelin Signaling: GOAT and GHS-R1a Take a LEAP in Complexity. Trends Endocrinol. Metab. 2020;31(2):107-117. https://doi.org/10.1016/j.tem.2019.09.006
52. Auclair N., Patey N., Melbouci L., Ou Y., Magri-Tomaz L. [et al.]. Acylated Ghrelin and The Regulation of Lipid Metabolism in The Intestine. Scientific Reports. 2019;9(1):17975. https://doi.org/10.1038/s41598-019-54265-0
53. Villarreal D., Pradhan G., Zhou Y., Xue B., Sun Y. Diverse and Complementary Effects of Ghrelin and Obestatin. Biomolecules. 2022;12(4):517. https://doi.org/10.3390/biom12040517
54. Ma Y., Zhang H., Guo W., Yu L. Potential role of ghrelin in the regulation of inflammation. FASEB Journal. 2022;36(9):e22508. https://doi.org/10.1096/fj.202200634r
55. Mathur N., Mehdi S. F., Anipindi M., Aziz M., Khan S. A. [et al.]. Ghrelin as an Anti-Sepsis Peptide: Review. Frontiers in Immunology. 2021;11:610363. https://doi.org/10.3389/fimmu.2020.610363

Keywords: ghrelin, leptin, growth hormone, agouti protein, obesity, appetite