Increase in Energy Intake Leads to a Decrease in Obestatin in Restricting-Type of Anorexia Nervosa

Abstract

Restricting-type of anorexia nervosa (AN-R) is a serious disorder affecting adolescents and young adults, and decreases quality of life over long period. Successful weight restoration is an important prognostic factor for disease outcome; however, the underlying mechanism of refeeding-resistance, a core psychopathology relevant to ‘ambivalent’ eating behaviors, remains unclear in this disorder. Obestatin plays an important role in the regulation of growth hormone release, appetite, and energy metabolism. However, the progress of these patients and changes in the levels of obestatin during treatment were not reported. The purpose of this study was to determine the changes in obestatin levels when energy intake increases in AN-R patients. As a result, obestatin was higher in AN-R patients than in control subjects as well as acyl ghrelin and des-acyl ghrelin. An increase in the intake calorie has decreased obestatin as well as des-acyl ghrelin. These findings indicate that the obestatin is an important factor in the diagnosis and treatment of AN-R, similarly to acyl ghrelin and des-acyl ghrelin. In the future, the research on the clinical application of the ghrelin peptide family and the receptor will be expected to progress.

Key words

eating disorders - energy intake - hospitalization - gut hormone

References

• 1 American Psychiatric Association .Diagnostic and statistical manual of mental disorders.. 4th edn. Washington, DC: American Psychiatric Association; 2000
• 2 Asakawa A, Inui A, Kaga T. et al . Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin.  Gastroenterology. 2001;  120 337-345
• 3 Chen CY, Asakawa A, Fujimiya M. et al . Ghrelin gene products and the regulation of food intake and gut motility.  Pharmacol Rev. 2009;  61 430-481
• 4 Chen CY, Fujimiya M, Asakawa A. et al . At the cutting edge: ghrelin gene products in food intake and gut motility.  Neuroendocrinology. 2009;  89 9-17
• 5 Chen CY, Fujimiya M, Laviano A. et al . Modulation of ingestive behavior and gastrointestinal motility by ghrelin in diabetic animals and humans.  J Chin Med Assoc. 2010;  73 225-229
• 6 Drossman DA, Ontjes DA, Heizer WD. Clinical conference. Anorexia nervosa.  Gastroenterology. 1979;  77 1115-1131
• 7 Fujimiya M, Asakawa A, Ataka K. et al . Ghrelin, des-acyl ghrelin, and obestatin: regulatory roles on the gastrointestinal motility.  Int J Pept. 2010;  305192
• 8 Fujino K, Inui A, Asakawa A. et al . Ghrelin induces fasted motor activity of the gastrointestinal tract in conscious fed rats.  J Physiol. 2003;  550 227-240
• 9 Fukushima M, Nakai Y, Taniguchi A. et al . Insulin sensitivity, insulin secretion, and glucose effectiveness in anorexia nervosa: a minimal model analysis.  Metabolism. 1993;  42 1164-1168
• 10 Gao XY, Kuang HY, Liu XM. et al . Decreased obestatin in plasma in metabolically obese, normal-weight men with normal glucose tolerance.  Diabetes Res Clin Pract. 2008;  79 e5-e6
• 11 Germain N, Galusca B, Grouselle D. et al . Ghrelin/obestatin ratio in two populations with low bodyweight: constitutional thinness and anorexia nervosa.  Psychoneuroendocrinology. 2009;  34 413-419
• 12 Gourcerol G, Million M, Adelson DW. et al . Lack of interaction between peripheral injection of CCK and obestatin in the regulation of gastric satiety signaling in rodents.  Peptides. 2006;  27 2811-2819
• 13 Harada T, Nakahara T, Yasuhara D. et al . Obestatin, acyl ghrelin, and des-acyl ghrelin responses to an oral glucose tolerance test in the restricting type of anorexia nervosa.  Biol Psychiatry. 2008;  63 245-247
• 14 Hosoda H, Kojima M, Matsuo H. et al . Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue.  Biochem Biophys Res Commun. 2000;  279 909-913
• 15 Hotta M, Ohwada R, Katakami H. et al . Plasma levels of intact and degraded ghrelin and their responses to glucose infusion in anorexia nervosa.  J Clin Endocrinol Metab. 2004;  89 5707-5712
• 16 Inhoff T, Mönnikes H, Noetzel S. et al . Desacyl ghrelin inhibits the orexigenic effect of peripherally injected ghrelin in rats.  Peptides. 2008;  29 2159-2168
• 17 Inui A. Ghrelin: an orexigenic and somatotrophic signal from the stomach.  Nat Rev Neurosci. 2001;  2 551-560
• 18 Kojima M, Hosoda H, Date Y. et al . Ghrelin is a growth-hormone-releasing acylated peptide from stomach.  Nature. 1999;  402 656-660
• 19 Li ZF, Guo ZF, Yang SG. et al . Circulating ghrelin and ghrelin to obestatin ratio are low in patients with untreated mild-to-moderate hypertension.  Regul Pept. 2010;  165 206-209
• 20 Lippl F, Erdmann J, Lichter N. et al . Relation of plasma obestatin levels to bmi, gender, age and insulin.  Horm Metab Res. 2008;  40 806-812
• 21 Martini AC, Fernández-Fernández R, Tovar S. et al . Comparative analysis of the effects of ghrelin and unacylated ghrelin on luteinizing hormone secretion in male rats.  Endocrinology. 2006;  147 2374-2382
• 22 Matsuda K, Miura T, Kaiya H. et al . Regulation of food intake by acyl and des-acyl ghrelins in the goldfish.  Peptides. 2006;  27 2321-2325
• 23 Nakahara T, Harada T, Yasuhara D. et al . Plasma obestatin concentrations are negatively correlated with body mass index, insulin resistance index, and plasma leptin concentrations in obesity and anorexia nervosa.  Biol Psychiatry. 2008;  64 252-255
• 24 Nakazato M, Murakami N, Date Y. et al . A role for ghrelin in the central regulation of feeding.  Nature. 2001;  409 194-198
• 25 Nogueiras R, Pfluger P, Tovar S. et al . Effects of obestatin on energy balance and growth hormone secretion in rodents.  Endocrinology. 2007;  148 21-26
• 26 Nozaki T, Tamai H, Matsubayashi S. et al . Insulin response to intravenous glucose in patients with anorexia nervosa showing low insulin response to oral glucose.  J Clin Endocrinol Metab. 1994;  79 217-222
• 27 Otto B, Tschöp M, Heldwein W. et al . Endogenous and exogenous glucocorticoids decrease plasma ghrelin in humans.  Eur J Endocrinol. 2004;  151 113-117
• 28 Qader SS, Håkanson R, Rehfeld JF. et al . Proghrelin-derived peptides influence the secretion of insulin, glucagon, pancreatic polypeptide and somatostatin: a study on isolated islets from mouse and rat pancreas.  Regul Pept. 2008;  146 230-237
• 29 Rauh M, Gröschl M, Rascher W. Simultaneous quantification of ghrelin and desacyl-ghrelin by liquid chromatography-tandem mass spectrometry in plasma, serum, and cell supernatants.  Clin Chem. 2007;  53 902-910
• 30 Samson WK, White MM, Price C. et al . Obestatin acts in brain to inhibit thirst.  Am J Physiol Regul Integr Comp Physiol. 2007;  292 637-643
• 31 Sedláčková D, Kopečková J, Papežová H. et al . Changes of plasma obestatin, ghrelin and NPY in anorexia and bulimia nervosa patients before and after a high-carbohydrate breakfast.  Physiol Res. 2011;  60 165-173
• 32 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;  87 240-244
• 33 Steinhausen HC. The outcome of anorexia nervosa in the 20^th century.  Am J Psychiatry. 2002;  159 1284-1293
• 34 St-Pierre DH, Settanni F, Olivetti I. et al . Circulating obestatin levels in normal and Type 2 diabetic subjects.  J Endocrinol Invest. 2010;  33 211-214
• 35 Takaya K, Ariyasu H, Kanamoto N. et al . Ghrelin strongly stimulates growth hormone release in humans.  J Clin Endocrinol Metab. 2000;  85 4908-4911
• 36 Tanaka M, Tatebe Y, Nakahara T. et al . Eating pattern and the effect of oral glucose on ghrelin and insulin secretion in patients with anorexia nervosa.  Clin Endocrinol (Oxf). 2003;  59 574-579
• 37 Tschöp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents.  Nature. 2000;  407 908-913
• 38 Yasuhara D, Naruo T, Nagai N. et al . Insulinogenic index at 15 min as a marker of nutritional rehabilitation in anorexia nervosa.  Am J Clin Nutr. 2003;  77 292-299
• 39 Yasuhara D, Naruo T, Nagai N. et al . Glucose tolerance predicts short-term refeeding outcome in females with anorexia nervosa.  Psychosom Med. 2005;  67 669-676
• 40 Zhang JV, Ren PG, Avsian-Kretchmer O. et al . Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake.  Science. 2005;  310 996-999
• 41 Zou CC, Liang L, Wang CL. et al . The change in ghrelin and obestatin levels in obese children after weight reduction.  Acta Paediatr. 2009;  98 159-165

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