Tuncay KÜME, Korcan DEMİR, Ece BÖBER, Gönül ÇATLI, Ayhan ABACI, Hale TUHAN, Sezer ACAR, Özlem GÜRSOY ÇALAN

Increased concentrations of serum nesfatin-1 levels in childhood with idiopathic chronic malnutrition

Background/aim: Nesfatin-1, an anorexigenic molecule, seems to play a role in appetite regulation and energy homeostasis. The goalof this study was to evaluate the relation of nesfatin-1 with anthropometric and metabolic (ghrelin, leptin) parameters in children withidiopathic chronic malnutrition.Materials and methods: The study included 37 underweight and 38 healthy children who were similar regarding age, sex, and pubertalstatus. Anthropometric and biochemical (nesfatin-1, ghrelin, and leptin levels) variables were assessed.Results: A total of 37 underweight subjects (mean age 10.5 ± 2.6 years) and 38 heathy subjects (mean age 10.3 ± 2.3 years) wererecruited. Underweight children had significantly higher nesfatin-1 (2.76 ± 0.4 vs. 1.56 ± 0.7, P < 0.001) and lower leptin levels (2.21 ±2.0 vs. 5.21 ± 2.4, P < 0.001) than those of the control subjects. Nesfatin-1 levels were significantly associated with only leptin levels, afteradjusting for age and BMI (r = –0.371, P = 0.001).Conclusion: The present study is the first to evaluate nesfatin-1 levels in relation with anthropometric and metabolic parameters inchildren with chronic malnutrition, who were subsequently found to have significantly higher nesfatin-1 levels. Our study underlinesthat nesfatin-1 may play a role in the development of malnutrition by inhibiting food intake in children.

PDF

___

Sawaya AL, Martins PA, Grillo LP, Florencio TT. Long-term effects of early malnutrition on body weight regulation. Nutr Rev 2004; 62: 127-133.
Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol 2005; 184: 291-318.
Cone RD, Cowley MA, Butler AA, Fan W, Marks DL, Low MJ. The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. Int J Obes Relat Metab Disord 2001; 25 Suppl 5: 63-67.
Oh IS, Shimizu H, Satoh T, Okada S, Adachi S, Inoue K, Eguchi H, Yamamoto M, Imaki T, Hashimoto K et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature 2006; 443: 709-712.
Stengel A, Goebel M, Wang L, Rivier J, Kobelt P, Monnikes H, Lambrecht NW, Tache Y. Central nesfatin-1 reduces darkphase food intake and gastric emptying in rats: differential role of corticotropin-releasing factor2 receptor. Endocrinology 2009; 150: 4911-4919.
Yosten GL, Samson WK. Nesfatin-1 exerts cardiovascular actions in brain: possible interaction with the central melanocortin system. Am J Physiol Regul Integr Comp Physiol 2009; 297: 330-336.
Cowley MA, Grove KL. To be or NUCB2, is nesfatin the answer? Cell Metab 2006; 4: 421-422.
Garcia-Galiano D, Navarro VM, Gaytan F, Tena-Sempere M. Expanding roles of NUCB2/nesfatin-1 in neuroendocrine regulation. J Mol Endocrinol 2010; 45: 281-290.
Stengel A, Tache Y. Role of brain NUCB2/nesfatin-1 in the regulation of food intake. Curr Pharm Des 2013; 19: 6955-6959.
Guo FF, Xu L, Gao SL, Sun XR, Li ZL, Gong YL. The effects of nesfatin-1 in the paraventricular nucleus on gastric motility and its potential regulation by the lateral hypothalamic area in rats. J Neurochem 2015; 132: 266-275.
Wang Q, Guo F, Sun X, Gao S, Li Z, Gong Y, Xu L. Effects of exogenous nesfatin-1 on gastric distention-sensitive neurons in the central nucleus of the amygdala and gastric motility in rats. Neurosci Lett 2014; 5 82: 65-70.
Kaba S, Karaman K, Komuroglu U, K AB, Demir N, Kocaman S, Dogan M, Ceylan N. Role of circulating nesfatin-1 in the underweight children with poor appetite. Eur Rev Med Pharmacol Sci 2015; 19: 4703-4706.
Ustabas Kahraman F, Vehapoglu A, Ozgen IT, Terzioglu S, Cesur Y, Dundaroz R. Correlation of brain neuropeptide (nesfatin-1 and orexin-A) concentrations with anthropometric and biochemical parameters in malnourished children. J Clin Res Pediatr Endocrinol 2015; 7: 197-202.
Denroche HC, Huynh FK, Kieffer TJ. The role of leptin in glucose homeostasis. J Diabetes Investig 2012; 3: 115-129.
Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763-770.
Hassink SG, Sheslow DV, de Lancey E, Opentanova I, Considine RV, Caro JF. Serum leptin in children with obesity: relationship to gender and development. Pediatrics 1996; 98: 201- 203.
Singhal A, Farooqi IS, O’Rahilly S, Cole TJ, Fewtrell M, Lucas A. Early nutrition and leptin concentrations in later life. Am J Clin Nutr 2002; 75: 993-999.
Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334: 292-295.
Schrauwen P, van Marken Lichtenbelt WD, Westerterp KR, Saris WH. Effect of diet composition on leptin concentration in lean subjects. Metabolism 1997; 46: 420-424.
Soliman AT, ElZalabany MM, Salama M, Ansari BM. Serum leptin concentrations during severe protein-energy malnutrition: correlation with growth parameters and endocrine function. Metabolism 2000; 49: 819-825.
Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001; 86: 5992.
Fagerberg B, Hulten LM, Hulthe J. Plasma ghrelin, body fat, insulin resistance, and smoking in clinically healthy men: the atherosclerosis and insulin resistance study. Metabolism 2003; 52: 1460-1463.
Morpurgo PS, Resnik M, Agosti F, Cappiello V, Sartorio A, Spada A. Ghrelin secretion in severely obese subjects before and after a 3-week integrated body mass reduction program. J Endocrinol Invest 2003; 26: 723-727.
Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, Wei R, Curtin LR, Roche AF, Johnson CL. 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 11 2002: 1-190.
Waterlow JC. Classification and definition of protein-calorie malnutrition. Br Med J 1972; 3: 566-569.
Waterlow JC. Note on the assessment and classification of protein-energy malnutrition in children. Lancet 1973; 2: 87-89.
Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 1976; 51: 170-179.
Goebel-Stengel M, Wang L. Central and peripheral expression and distribution of NUCB2/nesfatin-1. Curr Pharm Des 2013; 19: 6935-6940.
Price TO, Samson WK, Niehoff ML, Banks WA. Permeability of the blood-brain barrier to a novel satiety molecule nesfatin-1. Peptides 2007; 28: 2372-2381.
Stengel A, Tache Y. Nesfatin-1—role as possible new potent regulator of food intake. Regul Pept 2010; 163: 18-23.
Mortazavi S, Gonzalez R, Ceddia R, Unniappan S. Long-term infusion of nesfatin-1 causes a sustained regulation of wholebody energy homeostasis of male Fischer 344 rats. Front Cell Dev Biol 2015; 3: 22.
Abaci A, Catli G, Anik A, Kume T, Bober E. The relation of serum nesfatin-1 level with metabolic and clinical parameters in obese and healthy children. Pediatr Diabetes 2013; 14: 189-195.
Anwar GM, Yamamah G, Ibrahim A, El-Lebedy D, Farid TM, Mahmoud R. Nesfatin-1 in childhood and adolescent obesity and its association with food intake, body composition and insulin resistance. Regul Pept 2014; 188: 21-24.
Tan BK, Hallschmid M, Kern W, Lehnert H, Randeva HS. Decreased cerebrospinal fluid/plasma ratio of the novel satiety molecule, nesfatin-1/NUCB-2, in obese humans: evidence of nesfatin-1/NUCB-2 resistance and implications for obesity treatment. J Clin Endocrinol Metab 2011; 96: 669-673.
Ramanjaneya M, Chen J, Brown JE, Tripathi G, Hallschmid M, Patel S, Kern W, Hillhouse EW, Lehnert H, Tan BK et al. Identification of nesfatin-1 in human and murine adipose tissue: a novel depot-specific adipokine with increased levels in obesity. Endocrinology 2010; 151: 3169-3180.
Zegers D, Beckers S, Mertens IL, Van Gaal LF, Van Hul W. Association between polymorphisms of the Nesfatin gene, NUCB2, and obesity in men. Mol Genet Metab 2011; 103: 282- 286.
Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev 2005; 85: 495-522.
Whatmore AJ, Hall CM, Jones J, Westwood M, Clayton PE. Ghrelin concentrations in healthy children and adolescents. Clin Endocrinol (Oxf) 2003; 59: 649-654.
Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T, Suda M, Koh T, Natsui K, Toyooka S et al. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab 2001; 86: 4753-4758.
Otto B, Cuntz U, Fruehauf E, Wawarta R, Folwaczny C, Riepl RL, Heiman ML, Lehnert P, Fichter M, Tschop M. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol 2001; 145: 669-673.
Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes 2001; 50: 707-709.
Haluzik M, Kabrt J, Nedvidkova J, Svobodova J, Kotrlikova E, Papezova H. Relationship of serum leptin levels and selected nutritional parameters in patients with protein-caloric malnutrition. Nutrition 1999; 15: 829-833.
Hill KK, Hill DB, McClain MP, Humphries LL, McClain CJ. Serum insulin-like growth factor-I concentrations in the recovery of patients with anorexia nervosa. J Am Coll Nutr 1993; 12: 475-478.
Buyukgebiz B, Ozturk Y, Yilmaz S, Arslan N. Serum leptin concentrations in children with mild-to-moderate protein-energy malnutrition. Pediatr Int 2003; 45: 550-554.