eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
Current issue Archive Manuscripts accepted About the journal Special issues Editorial board Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
Clinical research

Circulating brain-derived neurotrophic factor, leptin, neuropeptide Y, and their clinical correlates in cystic fibrosis: a cross-sectional study

Jan K. Nowak, Mariusz Szczepanik, Magdalena Trypuć, Andrzej Pogorzelski, Waldemar Bobkowski, Marcin Grytczuk, Alina Minarowska, Rafał Wójciak, Jaroslaw Walkowiak

Arch Med Sci
Online publish date: 2018/04/23
View full text
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero
Cystic fibrosis (CF) involves chronic inflammation and decreased pulmonary function, which increase caloric demand. Yet, sufficient energy provision is hindered by reduced appetite and fat malabsorption. Brain-derived neurotrophic factor (BDNF), leptin, and neuropeptide Y (NPY) belong to energy balance-regulating factors. We aimed to assess their concentrations in CF patients in order to search for potential clinical correlates.

Material and methods
This was an exploratory, cross-sectional study. Patients’ weight and height Z-scores, forced expiratory volume in 1 s (FEV1%), exocrine pancreatic status (fecal elastase-1), genotypes, and other characteristics were assessed. Serum concentrations of BDNF, leptin, NPY, IL-6, and TNF-α were measured using ELISA.

The study enrolled 56 patients, of whom 29 (52%) were female and 17 (30%) were younger than 16 years. Median (1st–3rd quartile) mass Z-score was –0.85 (–1.56–(–0.36)); median FEV1 was 70.5% (45.0–89.5); 48 (86%) patients had exocrine pancreatic insufficiency and 8 (14%) diabetes. Overall, median concentrations were: BDNF: 33.91 ng/ml (26.40–40.43), leptin: 12.05 ng/ml (8.93–17.77), NPY: 2.86 ng/ml (1.75–4.42). None of these factors correlated with mass Z-score, FEV1%, IL-6 or TNF-α. Leptin and NPY correlated negatively (ρ = –0.62, p = 3 × 10–7); BDNF/NPY ratio was associated with leptin (ρ = 0.54, p = 2 × 10–5), BDNF/leptin ratio correlated with NPY (ρ = 0.60, p = 1 × 10–6). In a multivariable regression analysis NPY was weakly, but independently, associated with FEV1%, and leptin with age.

BDNF and leptin were not associated with weight Z-score or FEV1%. Serum NPY concentrations seemed to be lower in CF patients with reduced pulmonary function independently of malnutrition and inflammation.


appetite, cachexia, malnutrition, inflammation, respiratory insufficiency

Turck D, Braegger CP, Colombo C, et al. ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis. Clin Nutr 2016; 35: 557-77.
Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci 2015; 11: 1164-78.
Han JC, Liu QR, Jones M, et al. Brain-derived neurotrophic factor and obesity in the WAGR syndrome. N Engl J Med 2008; 359: 918-27.
Speliotes EK, Willer CJ, Berndt SI, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010; 42: 937-48.
Dinoff A, Herrmann N, Swardfager W, Lanctôt KL. The effect of acute exercise on blood concentrations of brain-derived neurotrophic factor in healthy adults: a meta-analysis. Eur J Neurosci 2017; 46: 1635-46.
Rosenbaum M, Leibel RL. 20 years of leptin: role of leptin in energy homeostasis in humans. J Endocrinol 2014; 223: T83-96.
Leung L, Kang J, Rayyan E, et al. Decreased basal chloride secretion and altered cystic fibrosis transmembrane conductance regulatory protein, Villin, GLUT5 protein expression in jejunum from leptin-deficient mice. Diabetes Metab 2014; 7: 321-30.
Boguszewski MCS, Kamoi TO, Bento Radominski R, et al. Insulin-like growth factor-1, leptin, body composition, and clinical status interactions in children with cystic fibrosis. Horm Res 2007; 67: 250-6.
Cohen RI, Tsang D, Koenig S, Wilson D, McCloskey T, Chandra S. Plasma ghrelin and leptin in adult cystic
fibrosis patients. J Cyst Fibros 2008; 7: 398-402.
Arumugam R, LeBlanc A, Seilheimer DK, Hardin DS. Serum leptin and IGF-I levels in cystic fibrosis. Endocr Res 1998; 24: 247-57.
Ziai S, Belson L, Malet A, et al. The association between leptin and insulin levels in adults with cystic fibrosis. Diabetes Metab 2012; 38: 34-9.
Stylianou C, Galli-Tsinopoulou A, Koliakos G, Fotoulaki M, Nousia-Arvanitakis S. Ghrelin and leptin levels in young adults with cystic fibrosis: relationship with body fat. J Cyst Fibros 2007; 6: 293-6.
Monajemzadeh M, Ashtiani MTH, Sadrian E, et al. Variation in plasma leptin levels in young Iranian children with cystic fibrosis. Arch Med Sci 2013; 9: 883-7.
Ahme ML, Ong KK, Thomson AH, Dunger DB. Reduced gains in fat and fat-free mass, and elevated leptin levels in children and adolescents with cystic fibrosis. Acta Paediatr 2004; 93: 1185-91.
Schmitt-Grohé S, Hippe V, Igel M, et al. Serum leptin and cytokines in whole blood in relation to clinical and nutritional status in cystic fibrosis. J Pediatr Gastroenterol Nutr 2006; 43: 228-33.
Holzer P, Reichmann F, Farzi A. Neuropeptide Y, peptide YY and pancreatic polypeptide in the gut-brain axis. Neuropeptides 2012; 46: 261-74.
Walkowiak J. Assessment of maldigestion in cystic fibrosis. J Pediatr 2004; 145: 285-7.
Spitzer M, Wildenhain J, Rappsilber J, Tyers M. BoxPlotR: a web tool for generation of box plots. Nat Methods 2014; 11: 121-2.
Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 2009; 41: 1149-60.
Cohen RI, Chandra S, Koenig S, Tsang D, Wilson D, McCloskey T. Ghrelin receptor expression in lymphocytes isolated from adult cystic fibrosis patients. Respir Int Rev Thorac Dis 2010; 79: 141-6.
Monajemzadeh M, Mokhtari S, Motamed F, et al. Plasma ghrelin levels in children with cystic fibrosis and healthy children. Arch Med Sci 2013; 9: 93-7.
Cohen RI, Ginsberg N, Tsang D, Wann LC, Ye X, Liu SF. Association of nesfatin-1 and fat mass in cystic fibrosis. Respir Int Rev Thorac Dis 2013; 86: 312-7.
Guo Y, Su M, McNutt MA, Gu J. Expression and distribution of cystic fibrosis transmembrane conductance regulator in neurons of the human brain. J Histochem Cytochem 2009; 57: 1113-20.
Xue R, Gu H, Qiu Y, et al. Expression of cystic fibrosis transmembrane conductance regulator in ganglia of human gastrointestinal tract. Sci Rep 2016; 6: 30926.
Varness T, Seffrood EE, Connor EL, Rock MJ, Allen DB. Oxandrolone improves height velocity and BMI in patients with cystic fibrosis. Int J Pediatr Endocrinol 2009; 2009: 826895.
Yoshida T. Serum levels of mature brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in healthy subjects. Open Clin Chem J 2012; 5: 7-12.
Russo F, Chimienti G, Clemente C, Ferreri C, Orlando A, Riezzo G. A possible role for ghrelin, leptin, brain-derived neurotrophic factor and docosahexaenoic acid in reducing the quality of life of coeliac disease patients following a gluten-free diet. Eur J Nutr 2017; 56: 807-18.
Liu W, Han X, Zhou X, et al. Brain derived neurotrophic factor in newly diagnosed diabetes and prediabetes. Mol Cell Endocrinol 2016; 429: 106-13.
Monteleone P, Fabrazzo M, Martiadis V, Serritella C, Pannuto M, Maj M. Circulating brain-derived neurotrophic factor is decreased in women with anorexia and bulimia nervosa but not in women with binge-eating disorder: relationships to co-morbid depression, psychopathology and hormonal variables. Psychol Med 2005; 35:
Chimienti G, Mezzapesa A, Rotelli MT, Lupo L, Pepe G. Plasma concentrations but not serum concentrations of brain-derived neurotrophic factor are related to pro-inflammatory cytokines in patients undergoing major abdominal surgery. Clin Biochem 2012; 45: 631-6.
Kauer-Sant’Anna M, Kapczinski F, Andreazza AC, et al. Brain-derived neurotrophic factor and inflammatory markers in patients with early- vs. late-stage bipolar disorder. Int J Neuropsychopharmacol 2009; 12: 447-58.
Huang T, Gejl AK, Tarp J, Andersen LB, Peijs L, Bugge A. Cross-sectional associations of objectively measured physical activity with brain-derived neurotrophic factor in adolescents. Physiol Behav 2017; 171: 87-91.
Anusha K, Hettiaratchi UPK, Athiththan LV, Perera PPR. Inter-relationship of serum leptin levels with selected anthropometric parameters among a non-diabetic population: a cross-sectional study. Eat Weight Disord 2017 Jul 7; doi: 10.1007/s40519-017-0413-x.
Wang D, Gao L, Gong K, Chai Q, Wang G. Increased serum leptin level in overweight patients with colon carcinoma: a cross-sectional and prospective study. Mol Clin Oncol 2017; 6: 75-8.
Domínguez C, Vieites-Prado A, Pérez-Mato M, et al. Role of adipocytokines in the pathophysiology of migraine. A cross-sectional study. Cephalalgia 2017 Jan 1; doi: 10.1177/0333102417720213.
Huang Q, Liao J, Liu Y, Liang H, Ma P, Pan J. Plasma neuropeptide Y levels in Chinese patients with primary insomnia. Sleep Breath 2015; 19: 617-22.
Doniec Z, Pierzchała-Koziec K, Tomalak W, Kurzawa R. Serum level of leptin and neuropeptide Y in children with mild asthma [Polish]. Pneumonol Alergol Pol 2004; 72: 9-13.
Vats P, Singh SN, Singh VK, et al. Appetite regulatory peptides in Indian Antarctic expeditioners. Nutr Neurosci 2005; 8: 233-8.
Mpouzika MDA, Papathanassoglou EDE, Giannakopoulou M, et al. Altered serum stress neuropeptide levels in critically ill individuals and associations with lymphocyte populations. Neuropeptides 2013; 47: 25-36.
Quick links
© 2018 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe