Ghrelin. Also interesting for seniors?
Authors:
Martin Dúbrava; Jarmila Jánošiová
Authors‘ workplace:
I. klinika geriatrie, Lekárska fakulta, Univerzita Komenského, Univerzitná nemocnica, Bratislava, Slovenská republika
Published in:
Geriatrie a Gerontologie 2025, 14, č. 2: 65-70
Category:
Review Article
doi:
https://doi.org/10.61568/geri/50-6499/20250512/140517
Overview
The hormone ghrelin was discovered relatively recently (in 1999). Today, we perceive it mainly as one of the important regulators of food intake. In addition to its primary function (increasing the level of growth hormone), it is significantly pleiotropic: it induces a feeling of hunger, or rather appetite, participates in the perception of tastes, prepares the body for food intake (increases motility and secretion of the stomach), has many metabolic effects – reduces insulin secretion, inhibits lipolysis, induces lipogenesis, etc. The biological half-life of ghrelin is short, therefore, in the case of therapeutic use, its synthetic analogues – agonists are more likely to be considered. Currently, ghrelin, its agonists or antagonists are not routinely used in treatment (except for anamorelin – a ghrelin analogue in Japan), although clinical trials are underway with them. Based on existing knowledge, it can be reasonably assumed that they could be effective in the treatment of several important pathologies, such as sarcopenia, cachexia, obesity, Alzheimer’s and Parkinson’s diseases, coronary artery and chronic kidney disease and other pathological conditions with a high prevalence in elderly. In our literature, there has not yet been published information that would specifically relate to the relationship between ghrelin and age. In this article, we offer one possible insight into this area.
Keywords:
geriatrics – ghrelin
Sources
1. Bays HE, González-Campoy JM, Bray GA, et al. Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev Cardio-
vasc Ther 2008; 6(3): 343–368.
2. Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402(6762): 65– 660.
3. Yamada C, Hattori T, Ohnishi S, et al. Ghrelin enhancer, the latest evidence of rikkunshito. Front Nutr 2021; 8:761631.
4. Bukhari SNA. An insight into the multifunctional role of ghrelin and structure activity relationship studies of ghrelin receptor ligands with clinical trials. Eur J Med Chem 2022; 235: 114308.
5. Blatnik M, Soderstrom CI,
Dysinger M, et al. Prandial ghrelin attenuation provides evidence that des-acyl ghrelin may be an artifact of sample handling in human plasma. Bioanalysis 2012; 4(20): 2447–2455.
6. Nass R, Farhy LS, Liu J, et al. Age-dependent decline in acyl-ghrelin concentrations and reduced association of acyl-ghrelin and growth hormone in healthy older adults. J Clin Endocrinol Metab 2014; 99(2): 602–608.
7. Broglio F, Benso A, Castiglioni C, et al. The endocrine response to ghrelin as a function of gender in humans in young and elderly subjects. J Clin Endocrinol Metab 2003; 88(4): 1537–1542.
8. Brzozowski T, Konturek PC, Drozdowicz D, et al. Role of central and peripheral ghrelin in the mechanism of gastric mucosal defence. Inflammopharmacology 2005; 13(1–3): 4562.
9. Ginter G, Ceranowicz P, Warzecha Z. Protective and healing effects of ghrelin and risk of cancer in the digestive system. Int J Mol Sci 2021; 22(19): 10571.
10. Vestergaard ET, Møller N, Andersen
RF, et al. Acute intravenous acyl ghrelin infusion induces thirst but does not affect sodium excretion: two randomized, double-blind, placebo-controlled crossover studies in hypopituitary patients. Eur J Endocrinol 2019; 181(1): 23–30.
11. Egido EM, Rodriguez-Gallardo J, Silvestre RA, et al. Inhibitory effect of ghrelin on insulin and pancreatic somatostatin secretion. Eur J Endocrinol 2002; 146(2): 241–244.
12. Murata M, Okimura Y, Iida K, et al. Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells. J Biol Chem 2002; 277(7): 5667–5674.
13. Shiiya T, Nakazato M, Mizuta M, et al. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 2002; 87(1): 240–244.
14. Vestergaard ET, Jessen N, Møller N, et al. Acyl Ghrelin induces insulin resistance independently of GH, cortisol, and free fatty acids. Sci Rep 2017; 7: 42706.
15. Tschöp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000; 407(6806): 908 – 913.
16. Takaya K, Ariyasu H, Kanamoto N, et al. Ghrelin strongly stimulates growth hormone release in humans. J Clin Endocrinol Metab 2000; 85(12): 4908–4911.
17. Ibrahim Abdalla MM. Ghrelin – physiological functions and regulation. Eur Endocrinol 2015; 11(2): 90–95.
18. Harvey RE, Howard VG, Lemus MB, et al. The ghrelin/GOAT system regulates obesity-induced inflammation in male mice. Endocrinology 2017; 158(7): 2179–2189.
19. Zhou M, Aziz M, Ochani M, et al. The protective role of human ghrelin in sepsis: Restoration of CD4 T cell proliferation. PLoS One 2018; 13(7): e0201139.
20. Morgan AH, Rees DJ, Andrews ZB, et al. Ghrelin mediated neuroprotection – A possible therapy for Parkinson’s disease? Neuro-
pharmacology 2018;136(Pt B): 317–326.
21. Li E, Chung H, Kim Y, et al. Ghrelin directly stimulates adult hippo-
campal neurogenesis: implications for learning and memory. Endocr J 2013; 60(6): 781–789.
22. Fukushima N, Hanada R, Teranishi H, et al. Ghrelin directly regulates bone formation. J Bone Miner Res 2005; 20(5): 790–798.
23. Delhanty PJ, van der Eerden BC, van Leeuwen JP. Ghrelin and bone. Biofactors 2014; 40(1): 41–48.
24. Angelino E, Reano S, Bollo A, et al. Ghrelin knockout mice display defective skeletal muscle regeneration and impaired satellite cell self-renewal. Endocrine 2018; 62(1): 129–135.
25. Zhang X, Zeng Z, Liu Y, et al. Emerging relevance of ghrelin in programmed cell death and its application in diseases. Int J Mol Sci 2023; 24(24):17254.
26. Nagaya N, Moriya J, Yasumura Y, et al. Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Circulation 2004; 110(24): 3674–3679.
27. Soeki T, Kishimoto I, Schwenke DO, et al. Ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction. Am J Physiol Heart Circ Physiol 2008; 294(1): H426–432.
28. Nagaya N, Kojima M, Uematsu M, et al. Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regul Integr Comp Physiol 2001; 280(5): R1483–1487.
29. Zhang CJ, Bidlingmaier M, Altaye M, et al. Acute administration of acyl, but not desacyl ghrelin, decreases blood pressure in healthy humans. Eur J Endocrinol 2017; 176(2): 123–132.
30. Shimizu Y, Nagaya N, Teranishi Y, et al. Ghrelin improves endothelial dysfunction through growth hormone-independent mechanisms in rats. Biochem Biophys Res Commun 2003; 310(3): 830–835.
31. Han QQ, Huang HJ, Wang YL, et al. Ghrelin exhibited antidepressant and anxiolytic effect via the p38-MAPK signaling pathway in hippo-
campus. Prog Neuropsychopharmacol Biol Psychiatry 2019; 93: 11–20.
32. Neary NM, Small CJ, Wren AM, et al. Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial. J Clin Endocrinol Metab. 2004; 89(6): 2832–2836.
33. Strasser F, Lutz TA, Maeder MT, et al. Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study. Br J Cancer 2008; 98(2): 300–308.
34. Temel JS, Abernethy AP, Currow DC, et al. Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. Lancet Oncol 2016; 17(4): 519–531.
35. Currow DC, Maddocks M, Cella D, et al. Efficacy of anamorelin, a novel non-peptide ghrelin analogue, in patients with advanced non-small cell lung cancer (NSCLC) and cachexia-review and expert opinion. Int J Mol Sci 2018; 19(11): 34–71.
36. Pandey S, Bradley L, Del Fabbro E. Updates in cancer cachexia: clinical management and pharmacologic interventions. Cancers (Basel) 2024; 16(9): 1696.
37. Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med 2008; 149(9): 601–611.
38. Pöykkö SM, Kellokoski E, Hörkkö S, et al. Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes 2003; 52(10): 2546–2553.
39. Tack J, Depoortere I, Bisschops R, et al. Influence of ghrelin on gastric emptying and meal-related symptoms in idiopathic gastroparesis. Aliment Pharmacol Ther 2005; 22(9): 847–853.
40. Wo JM, Ejskjaer N, Hellström PM, et al. Randomised clinical trial: ghrelin agonist TZP-101 relieves gastroparesis associated with severe nausea and vomiting--randomised clinical study subset data. Aliment Pharmacol Ther 2011; 33(6): 679–688.
41. Bisht P, Dagar N, Kumar N, et al. Potential targets in constipation research: a review. Curr Drug Targets 2023; 24(3): 247–260.
42. Wu W, Zhu L, Dou Z, et al. Ghrelin in focus: dissecting its critical roles in gastrointestinal pathologies and therapies. Curr Issues Mol Biol 2024; 46(1): 948–
964.
43. Kasprzak A. Role of the ghrelin system in colorectal cancer. Int J Mol Sci 2022; 23(10): 5380.
44. Tuero C, Becerril S, Ezquerro S, et al. Molecular and cellular mechanisms underlying the hepatoprotective role of ghrelin against NAFLD progression. J Physiol Biochem 2023; 79(4): 833–849.
45. Ibrahim M, Khalife L, Abdel-Latif R, et al. Ghrelin hormone a new molecular modulator between obesity and glomerular damage. Mol Biol Rep 2023; 50(12): 10525–10533.
46. Yoshimoto A, Mori K, Sugawara A, et al. Plasma ghrelin and desacyl ghrelin concentrations in renal failure. J Am Soc Nephrol 2002; 13(11): 2748–2752.
47. Takeda R, Nishimatsu H, Suzuki E, et al. Ghrelin improves renal function in mice with ischemic acute renal failure. J Am Soc Nephrol 2006; 17(1): 113–121.
48. Sun GX, Ding R, Li M, et al. Ghrelin attenuates renal fibrosis and inflammation of obstructive nephropathy. J Urol 2015; 193(6): 2107–2115.
49. Luo FM, Liu XJ, Li SQ, et al. Circulating ghrelin in patients with chronic obstructive pulmonary disease. Nutrition 2005; 21(7-8): 793–798.
50. Uzum AK, Aydin MM, Tutuncu Y, et al. Serum ghrelin and adiponectin levels are increased but serum leptin level is unchanged in low weight chronic obstructive pulmonary disease patients. Eur J Intern Med 2014; 25(4): 364–369.
51. Kim JH, Lee CT, Yoon HI, et al. Relation of ghrelin, leptin and inflammatory markers to nutritional status in active pulmonary tuberculosis. Clin Nutr 2010; 29(4): 512–518.
52. Kodama T, Ashitani J, Matsumoto N, et al. Ghrelin treatment suppresses neutrophil-dominant inflammation in airways of patients with chronic respiratory infection. Pulm Pharmacol Ther 2008; 21(5): 774–779.
53. Huang CX, Yuan MJ, Huang H, et al. Ghrelin inhibits post-infarct myocardial remodeling and improves cardiac function through anti-inflammation effect. Peptides 2009; 30(12): 2286–2291.
54. Matsumoto M, Yasuda S, Miyazaki S, et al. Decreased serum ghrelin levels in patients with acute myocardial infarction. Tohoku J Exp Med 2013; 231(3): 235–242.
55. Gruzdeva O, Uchasova E, Belik E, et al. Lipid, adipokine and ghrelin levels in myocardial infarction patients with insulin resistance. BMC Cardiovasc Disord 2014; 14: 7.
56. Li ZF, Zhou DX, Pan WZ, et al. Circulating ghrelin was negatively correlated with pulmonary arterial pressure in atrial septal defect patients. Chin Med J (Engl) 2013; 126(20): 3936–3939.
57. Theodorakis N, Feretzakis G,
Kreouzi M, et al. Ghrelin: an emerging therapy for heart failure. Clin Endocrinol (Oxf) 2025; Jan 5, epub ahead of print.
58. Chen Y, Cao CP, Li CR, et al. Ghrelin modulates insulin sensitivity and tau phosphorylation in high glucose-induced hippocampal neurons. Biol Pharm Bull 2010; 33(7): 1165–1169.
59. Bulgarelli I, Tamiazzo L, Bresciani E, et al. Desacyl-ghrelin and synthetic GH-secretagogues modulate the production of inflammatory cytokines in mouse microglia cells stimulated by beta-amyloid fibrils. J Neurosci Res 2009; 87(12): 2718–2727.
60. Fan L, Mao C, Hu X, et al. New insights into the pathogenesis of Alzheime’s disease. Front Neurol 2020; 10: 1312.
61. Tian J, Wang T, Du H. Ghrelin system in Alzheimer’s disease. Curr Opin Neurobiol 2023; 78:102655.
62. Pan X, Gao Y, Guan K, et al. Ghrelin/GHSR system in depressive disorder: pathologic roles and therapeutic implications. Curr Issues Mol Biol 2024; 46(7): 7324–7338.
63. Kore MS, Mamsa R, Patil D, et al. Ghrelin in depression: a promising therapeutic target. Mol Neurobiol 2024; Oct 18, epub ahead of print.
64. Lis M, Miłuch T, Majdowski M, et al. A link between ghrelin and major depressive disorder: a mini review. Front Psychiatry 2024; 15: 1367523.
65. Jiang H, Li LJ, Wang J, et al. Ghrelin antagonizes MPTP-induced neurotoxicity to the dopaminergic neurons in mouse substantia nigra. Exp Neurol 2008; 212(2): 532–537.
66. Dúbrava M, Šuba J ml., Jánošiová J. Leptín a adiponektín. Zaujímaví hráči aj u seniorov? Geriatra 2022; 28(1): 32–43.
67. Rhodes L, Zollers B, Wofford JA, et al. Capromorelin: a ghrelin receptor agonist and novel therapy for stimulation of appetite in dogs. Vet Med Sci 2017; 4(1): 3–
16.
68. Gortan Cappellari G, Zanetti M, Vinci P, et al. Unacylated ghrelin: a novel regulator of muscle intermediate metabolism with potential beneficial effects in chronic kidney disease. J Ren Nutr 2017; 27(6): 474–477.
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