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Acute effects of acylated and unacylated ghrelin on total and high molecular weight adiponectin in morbidly obese subjects

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Abstract

Background: Energy homeostasis and body weight are regulated by a highly complex network involving the brain, the digestive tract, and white adipose tissue (WAT). Knowledge about signaling pathways connecting digestive tract and WAT is limited. Gut hormone ghrelin and adipokine adiponectin are both decreased in obesity and they share a potent effect on insulin sensitivity: both adiponectin and the combination of acylated (AG) and unacylated ghrelin (UAG) improve insulin sensitivity. Aim: In the present study, we evaluated whether acute administration of UAG alone or combined with AG affects adiponectin concentrations. Subjects and methods: Eight morbidly obese non-diabetic subjects were treated with either UAG 200 μg, UAG 100 μg + AG 100 μg (Comb), or placebo in 3 episodes in a double blind randomized cross-over design. Study medication was administered as single iv bolus injections at 09:00 h after an overnight fast. High molecular weight (HMW) and total adiponectin, glucose, insulin, and total ghrelin and AG were measured up to 1 h after administration. Results: HMW and total adiponectin concentrations did not change after administration of either UAG or Comb, nor were they different from placebo. Insulin concentrations decreased significantly after acute administration of Comb, reaching a minimum at 20 min: 58.2±3.9% of baseline. Conclusions: Acute iv administration of UAG and the combination of UAG and AG in morbidly obese non-diabetic subjects without overt diabetes does not affect total or HMW adiponectin concentrations, neither directly nor indirectly by changing insulin concentrations.

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References

  1. Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol 2005, 184: 291–318.

    Article  PubMed  CAS  Google Scholar 

  2. Batterham RL, Cowley MA, Small CJ, et al. Gut hormone PYY(3–36) physiologically inhibits food intake. Nature 2002, 418: 650–4.

    Article  PubMed  CAS  Google Scholar 

  3. Asakawa A, Inui A, Yuzuriha H, et al. Characterization of the effects of pancreatic polypeptide in the regulation of energy balance. Gastroenterology 2003, 124: 1325–36.

    Article  PubMed  CAS  Google Scholar 

  4. Larsen PJ, Tang-Christensen M, Jessop DS. Central administration of glucagon-like peptide-1 activates hypothalamic neuroendocrine neurons in the rat. Endocrinology 1997, 138: 4445–55.

    PubMed  CAS  Google Scholar 

  5. Lutz TA, Mollet A, Rushing PA, Riediger T, Scharrer E. The anorectic effect of a chronic peripheral infusion of amylin is abolished in area postrema/nucleus of the solitary tract (AP/NTS) lesioned rats. Int J Obes Relat Metab Disord 2001, 25: 1005–11.

    Article  PubMed  CAS  Google Scholar 

  6. Murphy KG, Dhillo WS, Bloom SR. Gut peptides in the regulation of food intake and energy homeostasis. Endocr Rev 2006, 27: 719–27.

    Article  PubMed  CAS  Google Scholar 

  7. Nogueiras R, Lopez M, Dieguez C. Regulation of lipid metabolism by energy availability: a role for the central nervous system. Obes Rev 2010, 11: 185–201.

    Article  PubMed  CAS  Google Scholar 

  8. Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature 2001, 409: 194–8.

    Article  PubMed  CAS  Google Scholar 

  9. Shintani M, Ogawa Y, Ebihara K, et al. Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes 2001, 50: 227–32.

    Article  PubMed  CAS  Google Scholar 

  10. van der Lely AJ, Tschöp M, Heiman ML, Ghigo E. Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev 2004, 25: 426–57.

    Article  PubMed  CAS  Google Scholar 

  11. Wren AM, Small CJ, Ward HL, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 2000, 141: 4325–8.

    Article  PubMed  CAS  Google Scholar 

  12. Cheung CC, Clifton DK, Steiner RA. Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology 1997, 138: 4489–92.

    Article  PubMed  CAS  Google Scholar 

  13. Kamohara S, Burcelin R, Halaas JL, Friedman JM, Charron MJ. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 1997, 389: 374–7.

    Article  PubMed  CAS  Google Scholar 

  14. Schwartz MW, Seeley RJ, Campfield LA, Burn P, Baskin DG. Identification of targets of leptin action in rat hypothalamus. J Clin Invest 1996, 98: 1101–6.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  15. Ahima RS, Lazar MA. Adipokines and the peripheral and neural control of energy balance. Mol Endocrinol 2008, 22: 1023–31.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Ahima RS, Qi Y, Singhal NS, Jackson MB, Scherer PE. Brain adipocytokine action and metabolic regulation. Diabetes 2006, 55 (Suppl 2): S145–54.

    Article  PubMed  CAS  Google Scholar 

  17. Qi Y, Takahashi N, Hileman SM, et al. Adiponectin acts in the brain to decrease body weight. Nat Med 2004, 10: 524–9.

    Article  PubMed  CAS  Google Scholar 

  18. Tovar S, Nogueiras R, Tung LY, et al. Central administration of resistin promotes short-term satiety in rats. Eur J Endocrinol 2005, 153: R1–5.

    Article  PubMed  CAS  Google Scholar 

  19. Barazzoni R, Zanetti M, Stebel M, Biolo G, Cattin L, Guarnieri G. Hyperleptinemia prevents increased plasma ghrelin concentration during short-term moderate caloric restriction in rats. Gastroenterology 2003, 124: 1188–92.

    Article  PubMed  CAS  Google Scholar 

  20. Kamegai J, Tamura H, Shimizu T, Ishii S, Sugihara H, Oikawa S. Effects of insulin, leptin, and glucagon on ghrelin secretion from isolated perfused rat stomach. Regul Pept 2004, 119: 77–81.

    Article  PubMed  CAS  Google Scholar 

  21. Lejeune MP, Hukshorn CJ, Saris WH, Westerterp-Plantenga MS. Effects of very low calorie diet induced body weight loss with or without human pegylated recombinant leptin treatment on changes in ghrelin and adiponectin concentrations. Physiol Behav 2007, 91: 274–80.

    Article  PubMed  CAS  Google Scholar 

  22. Toshinai K, Mondal MS, Nakazato M, et al. Upregulation of Ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration. Biochem Biophys Res Commun 2001, 281: 1220–5.

    Article  PubMed  CAS  Google Scholar 

  23. Tschöp M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes 2001, 50: 707–9.

    Article  PubMed  Google Scholar 

  24. Weigle DS, Duell PB, Connor WE, Steiner RA, Soules MR, Kuijper JL. Effect of fasting, refeeding, and dietary fat restriction on plasma leptin levels. J Clin Endocrinol Metab 1997, 82: 561–5.

    PubMed  CAS  Google Scholar 

  25. Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999, 257: 79–83.

    Article  PubMed  CAS  Google Scholar 

  26. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996, 271: 10697–703.

    Article  PubMed  CAS  Google Scholar 

  27. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev 2005, 26: 439–51.

    Article  PubMed  CAS  Google Scholar 

  28. Broglio F, Arvat E, Benso A, et al. Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab 2001, 86: 5083–6.

    Article  PubMed  CAS  Google Scholar 

  29. Gauna C, Delhanty PJ, Hofland LJ, et al. Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. J Clin Endocrinol Metab 2005, 90: 1055–60.

    Article  PubMed  CAS  Google Scholar 

  30. van der Lely AJ. Ghrelin and new metabolic frontiers. Horm Res 2009, 71 (Suppl 1): 129–33.

    Article  PubMed  CAS  Google Scholar 

  31. Gauna C, Meyler FM, Janssen JA, et al. Administration of acylated ghrelin reduces insulin sensitivity, whereas the combination of acylated plus unacylated ghrelin strongly improves insulin sensitivity. J Clin Endocrinol Metab 2004, 89: 5035–42.

    Article  PubMed  CAS  Google Scholar 

  32. Kiewiet RM, van Aken MO, van der Weerd K, et al. Effects of acute administration of acylated and unacylated ghrelin on glucose and insulin concentrations in morbidly obese subjects without overt diabetes. Eur J Endocrinol 2009, 161: 567–73.

    Article  PubMed  CAS  Google Scholar 

  33. Berg AH, Combs TP, Du X, Brownlee M, Scherer PE. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 2001, 7: 947–53.

    Article  PubMed  CAS  Google Scholar 

  34. Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001, 7: 941–6.

    Article  PubMed  CAS  Google Scholar 

  35. Nakashima R, Kamei N, Yamane K, Nakanishi S, Nakashima A, Kohno N. Decreased total and high molecular weight adiponectin are independent risk factors for the development of type 2 diabetes in Japanese-Americans. J Clin Endocrinol Metab 2006, 91: 3873–7.

    Article  PubMed  CAS  Google Scholar 

  36. Waki H, Yamauchi T, Kamon J, et al. Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 2003, 278: 40352–63.

    Article  PubMed  CAS  Google Scholar 

  37. National Institutes of Health NH, Lung, and Blood Institute. Clinical Guidelines of the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. Bethesda, Md: Nationale Institutes of Health, 1998.

  38. Barber TM, Hazell M, Christodoulides C, et al. Serum levels of retinol-binding protein 4 and adiponectin in women with polycystic ovary syndrome: associations with visceral fat but no evidence for fat mass-independent effects on pathogenesis in this condition. J Clin Endocrinol Metab 2008, 93: 2859–65.

    Article  PubMed  CAS  Google Scholar 

  39. Gnanapavan S, Kola B, Bustin SA, et al. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 2002, 87: 2988.

    Article  PubMed  CAS  Google Scholar 

  40. Rodriguez A, Gomez-Ambrosi J, Catalan V, et al. Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Int J Obes (Lond) 2009, 33: 541–52.

    Article  CAS  Google Scholar 

  41. Thompson NM, Gill DA, 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: 234–42.

    Article  PubMed  CAS  Google Scholar 

  42. Ott V, Fasshauer M, Dalski A, et al. Direct peripheral effects of ghrelin include suppression of adiponectin expression. Horm Metab Res 2002, 34: 640–5.

    Article  PubMed  CAS  Google Scholar 

  43. McLaughlin T, Abbasi F, Lamendola C, Frayo RS, Cummings DE. Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls. J Clin Endocrinol Metab 2004, 89: 1630–5.

    Article  PubMed  CAS  Google Scholar 

  44. Möhlig M, Wegewitz U, Osterhoff M, et al. Insulin decreases human adiponectin plasma levels. Horm Metab Res 2002, 34: 655–8.

    Article  PubMed  Google Scholar 

  45. Saad MF, Bernaba B, Hwu CM, et al. Insulin regulates plasma ghrelin concentration. J Clin Endocrinol Metab 2002, 87: 3997–4000.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Endocrinology, Department of Internal Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands

    R. M. Kiewiet MD, M. O. van Aken, K. van der Weerd, J. A. Visser, A. P. N. Themmen & A. J. van der Lely

  2. Protein and Peptides Laboratory, Oxford Brookes University, Oxford, UK

    M. J. Hazell

Authors
  1. R. M. Kiewiet MD
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  2. M. J. Hazell
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  3. M. O. van Aken
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  4. K. van der Weerd
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  5. J. A. Visser
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  6. A. P. N. Themmen
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  7. A. J. van der Lely
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Correspondence to R. M. Kiewiet MD.

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Kiewiet, R.M., Hazell, M.J., van Aken, M.O. et al. Acute effects of acylated and unacylated ghrelin on total and high molecular weight adiponectin in morbidly obese subjects. J Endocrinol Invest 34, 434–438 (2011). https://doi.org/10.1007/BF03346709

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