Advances in Clinical and Experimental Medicine

Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 6, June, p. 789–795

doi: 10.17219/acem/97403

Publication type: original article

Language: English

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Creative Commons BY-NC-ND 3.0 Open Access

Association of total, acylated and unacylated ghrelin with apolipoprotein A1 and insulin concentrations in acromegalic patients

Hanna Komarowska1,A,B,C,D,F, Barbara Bromińska1,B,C,F, Nadia Sawicka-Gutaj1,C,D,F, Magdalena Jaskula-Świtek1,B,F, Ryszard Waśko1,A, Marek Ruchała1,E,F, Gabriel Bromiński2,C,F, Małgorzata Kotwicka3,A,E,F

1 Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poland

2 Department of Urology and Urologic Oncology, Poznan University of Medical Sciences, Poland

3 Department of Cell Biology, Poznan University of Medical Sciences, Poland

Abstract

Background. Ghrelin is a hormone that occurs in acylated (AG) or unacylated (UG) form. Ghrelin strongly stimulates growth hormone (GH) secretion from anterior pituitary, as well as regulates the energy balance and various metabolic parameters. Increased consideration is given to UG, thought to be inactive.
Objectives. We aimed to evaluate the levels of total ghrelin, AG and UG in medically naive and treated patients with biochemically active acromegaly, with respect to variables of lipid and glucose metabolism.
Material and Methods. We studied total ghrelin, AG and calculated UG levels in a group of 24 patients with active acromegaly and 15 healthy controls. Plasma levels of GH, insulin-like growth factor 1 (IGF-1), insulin, glucose, total cholesterol (TC), high-density lipoprotein (HDL) cholesterol and calculated low-density lipoprotein (LDL) cholesterol, triglycerides (TG), apolipoproteins A1 (APO A1), and B-100 (APO B-100) were measured.
Results. Patients with acromegaly revealed lower levels of total ghrelin than healthy controls. In pooled data of all subgroups, simple linear regression analysis revealed that total ghrelin concentration was significantly associated with APO A1 concentration (β = 0.8087; p = 0.0315) and AG concentration was significantly associated with fasting insulin concentration (β = 15.5183; p = 0.011). There was an inverse association between UG and the patients’ age, and positive association between UG and APO A1.
Conclusion. Our results suggest that ghrelin may influence metabolic disturbances in acromegaly. It seems that the assessment of AG and UG is superior to total ghrelin measurement. Mechanisms regulating ghrelin acylation and function of each form need elucidation in order to improve diagnostics and treatment of metabolic disturbances, not only acromegaly.

Key words

ghrelin, acromegaly, apolipoprotein A-1, apolipoprotein B-100

References (40)

  1. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656–660. doi:10.1038/45230
  2. Kojima M, Kangawa K. Ghrelin: Structure and function. Physiol Rev. 2005;85(2):495–522. doi:10.1152/physrev.00012.2004
  3. Varela L, Vázquez MJ, Cordido F, et al. Ghrelin and lipid metabolism: Key partners in energy balance. J Mol Endocrinol. 2011;46(2):R43–63. doi:10.1677/JME-10-0068
  4. Harisseh R, Pillot B, Gharib A, et al. Unacylated ghrelin analog prevents myocardial reperfusion injury independently of permeability transition pore. Basic Res Cardiol. 2017;112(1):4. doi:10.1007/s00395-016-0595-9
  5. Au CC, Furness JB, Brown KA. Ghrelin and breast cancer: Emerging roles in obesity, estrogen regulation, and cancer. Front Oncol. 2016;6:265. doi:10.3389/fonc.2016.00265
  6. Feingold KR, Grunfeld C. Introduction to lipids and lipoproteins. In: De Groot LJ, Chrousos G, Dungan K, et al., eds. Endotext. South Dartmouth, MA: MDText.com, Inc.; 2000. http://www.ncbi.nlm.nih.gov/books/NBK305896/. Accessed June 12, 2018.
  7. Manjunath CN, Rawal JR, Irani PM, Madhu K. Atherogenic dyslipidemia. Indian J Endocrinol Metab. 2013;17(6):969–976. doi:10.4103/2230-8210.122600
  8. Pivonello R, Auriemma RS, Grasso LFS, et al. Complications of acromegaly: Cardiovascular, respiratory and metabolic comorbidities. Pituitary. 2017;20(1):46–62. doi:10.1007/s11102-017-0797-7
  9. Găloiu S, Poiană C. Current therapies and mortality in acromegaly. J Med Life. 2015;8(4):411–415.
  10. Katznelson L, Laws ER, Melmed S, et al. Acromegaly: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933–3951. doi:10.1210/jc.2014-2700
  11. Miranda-Rius J, Brunet-LLobet L, Lahor-Soler E, et al. GH-secreting pituitary macroadenoma (acromegaly) associated with progressive dental malocclusion and refractory CPAP treatment. Head Face Med. 2017;13(1):7. doi:10.1186/s13005-017-0140-6
  12. Leite-Moreira AF, Soares J-B. Physiological, pathological and potential therapeutic roles of ghrelin. Drug Discov Today. 2007;12(7–8):276–288. doi:10.1016/j.drudis.2007.02.009
  13. Jaskula M, Wasko R, Komarowska H, Dziubandowska A, Sowinski J. Serum ghrelin levels and disturbances of the lipid profile in patients with acromegaly. Neuro Endocrinol Lett. 2009;30(2):245–255.
  14. Jarkovská Z, Rosická M, Marek J, et al. Plasma levels of total and active ghrelin in acromegaly and growth hormone deficiency. Physiol Res. 2006;55(2):175–181.
  15. Freda PU, Reyes CM, Conwell IM, Sundeen RE, Wardlaw SL. Serum ghrelin levels in acromegaly: Effects of surgical and long-acting octreotide therapy. J Clin Endocrinol Metab. 2003;88(5):2037–2044. doi:10.1210/jc.2002-021683
  16. Kawamata T, Inui A, Hosoda H, Kangawa K, Hori T. Perioperative plasma active and total ghrelin levels are reduced in acromegaly when com-pared with in nonfunctioning pituitary tumors even after normalization of serum GH. Clin Endocrinol (Oxf). 2007;67(1):140–144. doi:10.1111/j.1365-2265.2007.02851.x
  17. Reyes-Vidal C, Fernandez JC, Bruce JN, et al. Prospective study of surgical treatment of acromegaly: Effects on ghrelin, weight, adiposity, and markers of CV risk. J Clin Endocrinol Metab. 2014;99(11):4124–4132. doi:10.1210/jc.2014-2259
  18. Wasko R, Jaskula M, Komarowska H, Zamyslowska H, Sowinski J, Waligorska-Stachura J. Ghrelin concentrations in acromegalic patients in relation to the administered therapy. Neuro Endocrinol Lett. 2006;27(1–2):162–168.
  19. Delhanty PJD, Huisman M, Julien M, et al. The acylated (AG) to unacylated (UAG) ghrelin ratio in esterase inhibitor-treated blood is higher than previously described. Clin Endocrinol (Oxf). 2015;82(1):142–146. doi:10.1111/cen.12489
  20. Kosowicz J, Baumann-Antczak A, Ruchała M, Gryczyńska M, Gurgul E, Sowiński J. Thyroid hormones affect plasma ghrelin and obestatin levels. Horm Metab Res. 2011;43(2):121–125. doi:10.1055/s-0030-1269853
  21. Özcan B, Neggers SJCMM, Miller AR, et al. Does des-acyl ghrelin improve glycemic control in obese diabetic subjects by decreasing acylated ghrelin levels? Eur J Endocrinol. 2014;170(6):799–807. doi:10.1530/EJE-13-0347
  22. Delhanty PJ, Neggers SJ, van der Lely AJ. Des-acyl ghrelin: A metabolically active peptide. Endocr Dev. 2013;25:112–121. doi:10.1159/000346059
  23. Kleinz MJ, Maguire JJ, Skepper JN, Davenport AP. Functional and immunocytochemical evidence for a role of ghrelin and des-octa­noyl ghrelin in the regulation of vascular tone in man. Cardiovasc Res. 2006;69(1):227–235. doi:10.1016/j.cardiores.2005.09.001
  24. Thompson NM, Gill DAS, Davies R, et al. Ghrelin and des-octa­noyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor. Endocrinology. 2004;145(1):234–242. doi:10.1210/en.2003-0899
  25. Cederberg H, Rajala U, Koivisto V-M, et al. Unacylated ghrelin is associated with changes in body composition and body fat distribution during long-term exercise intervention. Eur J Endocrinol. 2011;165(2):243–248. doi:10.1530/EJE-11-0334
  26. Muhammad A, Delhanty PJD, Huisman M, Visser JA, Jan van der Lelij A, Neggers SJCMM. The acylated/unacylated ghrelin ratio is similar in patients with acromegaly during different treatment regimens. J Clin Endocrinol Metab. 2017;102(7):2425–2432. doi:10.1210/jc.2017-00147
  27. Miya A, Nakamura A, Miyoshi H, et al. Glucose tolerance is improved following surgery for silent somatotroph adenoma. International Journal of Diabetes and Clinical Research. 2015;2:6–12.
  28. Cappiello V, Ronchi C, Morpurgo PS, et al. Circulating ghrelin levels in basal conditions and during glucose tolerance test in acromegalic patients. Eur J Endocrinol. 2002;147(2):189–194.
  29. Barazzoni R, Gortan Cappellari G, Semolic A, et al. Plasma total and unacylated ghrelin predict 5-year changes in insulin resistance. Clin Nutr. 2016;35(5):1168–1173. doi:10.1016/j.clnu.2015.10.002
  30. González CR, Vázquez MJ, López M, Diéguez C. Influence of chronic undernutrition and leptin on GOAT mRNA levels in rat stomach mucosa. J Mol Endocrinol. 2008;41(6):415–421. doi:10.1677/JME-08-0102
  31. Khatib MN, Gaidhane S, Gaidhane AM, Simkhada P, Zahiruddin QS. Ghrelin O acyl transferase (GOAT) as a novel metabolic regulatory enzyme. J Clin Diagn Res. 2015;9(2):LE01–05. doi:10.7860/JCDR/2015/9787.5514
  32. Lim CT, Kola B, Grossman A, Korbonits M. The expression of ghrelin O-acyltransferase (GOAT) in human tissues. Endocr J. 2011;58(8):707–710.
  33. Kouno T, Akiyama N, Fujieda K, et al. Reduced intake of carbohydrate prevents the development of obesity and impaired glucose metabolism in ghrelin O-acyltransferase knockout mice. Peptides. 2016;86:145–152. doi:10.1016/j.peptides.2016.11.003
  34. Barnett BP, Hwang Y, Taylor MS, et al. Glucose and weight control in mice with a designed ghrelin O-acyltransferase inhibitor. Science. 2010;330(6011):1689–1692. doi:10.1126/science.1196154
  35. Teuffel P, Wang L, Prinz P, et al. Treatment with the ghrelin-O-acyltransferase (GOAT) inhibitor GO-CoA-Tat reduces food intake by reducing meal frequency in rats. J Physiol Pharmacol. 2015;66(4):493–503.
  36. Ritze Y, Schollenberger A, Hamze Sinno M, et al. Gastric ghrelin, GOAT, leptin, and leptinR expression as well as peripheral serotonin are dysregulated in humans with obesity. Neurogastroenterol Motil. 2016;28(6):806–815. doi:10.1111/nmo.12773
  37. Mihalache L, Gherasim A, Niță O, et al. Effects of ghrelin in energy balance and body weight homeostasis. Hormones (Athens). 2016;15(2):186–196. doi:10.14310/horm.2002.1672
  38. Hopkins AL, Nelson TAS, Guschina IA, et al. Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R1a activity: Evidence for target cell-induced acylation. Sci Rep. 2017;7:45541. doi:10.1038/srep45541
  39. De Vriese C, Hacquebard M, Gregoire F, Carpentier Y, Delporte C. Ghrelin interacts with human plasma lipoproteins. Endocrinology. 2007;148(5):2355–2362. doi:10.1210/en.2006-1281
  40. Purnell JQ, Weigle DS, Breen P, Cummings DE. Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein choles-terol, but not with gender, menopausal status, or cortisol levels in humans. J Clin Endocrinol Metab. 2003;88(12):5747–5752. doi:10.1210/jc.2003-030513