Background: The role of brain-derived neurotrophic factor (BDNF) variants on change in body weight and cardiovascular risk factors after weight loss remains unclear in obese patients. Objective: Our aim was to analyze the effects of the rs10767664 BDNF gene polymorphism on body weight, cardiovascular risk factors, and serum adipokine levels after a high monounsaturated fatty acids (MUFAs) hypocaloric diet (diet M) versus a high polyunsaturated fatty acids (PUFAs) hypocaloric diet (diet P). Methods: A Caucasian population of 361 obese patients was enrolled. Subjects who met the inclusion criteria were randomly allocated to one of two diets for a period of 3 months. Results: Two hundred and sixteen subjects (59.8%) had the genotype AA (wild-type group), and 145 (40.2%) patients had the genotypes AT (122 patients, 33.8%) or TT (23 patients, 6.4%) (mutant-type group). After weight loss with diet P and diet M and in both genotype groups, body mass index, weight, fat mass, waist circumference, systolic blood pressure, serum leptin levels, low-density lipoprotein cholesterol, and total cholesterol decreased in a significant way. Secondary to weight loss with diet M and only in the wild-type group, insulin levels (-2.1 ± 2.0 vs. -0.7 ± 2.9 IU/L, p < 0.05) and homeostatic model assessment of insulin resistance (-0.7 ± 0.9 vs. -0.3 ± 1.0 U, p < 0.05) decreased. Conclusion: Our data show that the rs10767664 variant of the BDNF gene modifies insulin resistance and insulin levels after weight loss with a hypocaloric diet enriched with MUFAs.

1.
Guh DP, Zhang W, Bansback N: The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health 2009;9:88-101.
2.
Loos RJ, Bouchard C: Obesity - is it a genetic disorder? J Intern Med 2003;254:401-425.
3.
Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, et al: Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 2009;41:18-24.
4.
Nawa H, Carnahan C: BDNF protein measured by a novel enzyme immunoassay in normal brain and after seizure: partial disagreement with mRNA levels. Eur J Neursosci 1995;7:1527-1535.
5.
Kernie SG, Liebl DL, Parada LF: BDNF regulates eating behavior and locomotor activity in mice. EMBO J 2000;19:1290-1300.
6.
Gunstad J, Schofield P, Paul RH, Spitznagel MB, Cohen RA, Williams LM, et al: BDNF Val66Met polymorphism is associated with body mass index in healthy adults. Neuropsychobiology 2006;53:153-156.
7.
Shugart YY, Chen L, Day IN, Lewis SJ, Timpson NJ, Yuan W, et al: Two British women studies replicated the association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) and BMI. Eur J Hum Genet 2009;17:1050-1055.
8.
Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, et al: Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010;42:937-948.
9.
Friedel S, Horro FF, Wermter AK, Geller F, Dempfle A, Reichwald K, et al: Mutation screen of the brain derived neurotrophic factor gene (BDNF): identification of several genetic variants and association studies in patients with obesity, eating disorders, and attention-deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 2005;132B:96-99.
10.
Alharbi KK, Richardson TG, Khan IA, Syed R, Mohammed AK, Boustred CR, et al: Influence of adiposity-related genetic markers in a population of Saudi Arabians where other variables influencing obesity may be reduced. Dis Markers 2014;2014:758232.
11.
Mataix J, Mañas M: Tablas de composición de alimentos españoles. Granada, University of Granada, 2003.
12.
Duart Duart MJ, Arroyo CO, Moreno Frígols JL: Validation of a kinetic model for the reactions in RIA. Clin Chem Lab Med 2002;40:1161-1167.
13.
Mathews DR, Hosker JP, Rudenski AS: Homeostasis model assessment: insulin resistance and beta cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-414.
14.
Pfutzner A, Langefeld M, Kunt T: Evaluation of human resistin assays with serum from patients with type 2 diabetes and different degrees of insulin resistance. Clin Lab 2003;49:571-576.
15.
Meier U, Gressner M: Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem 2004;50:1511-1525.
16.
Lukaski H, Johnson PE: Assessment of fat-free mass using bioelectrical impedance measurements of the human body. Am J Clin Nutr 1985;41:810-817.
17.
de Luis DA, Izaola O, Primo D, Pacheco D: Effect of the rs10767664 variant of the brain-derived neurotrophic factor gene on weight change and cardiovascular risk factors in morbidly obese patients after biliopancreatic diversion surgery. J Nutrigenet Nutrigenomics 2016;9:116-122.
18.
Merhi ZO, Minkoff H, Lambert-Messerlian GM, Macura J, Feldman J, Seifer DB: Plasma brain-derived neurotrophic factor in women after bariatric surgery: a pilot study. Fertil Steril 2009;91(4 suppl):1544-1548.
19.
Fujinami A, Ohta K, Obayashi H: Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: relationship to glucose metabolism and biomarkers of insulin resistance. Clin Biochem 2008;41:812-817.
20.
Thoenen H: Neurotrophins and neuronal plasticity. Science 1995;270:593-598.
21.
Ribasés M, Gratacòs M, Armengol L, de Cid R, Badía A, Jiménez L, et al: Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type. Mol Psychiatry 2003;8:745-751.
22.
Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, et al: The BDNF Val66Met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 2003;112:257-269.
23.
Duan W, Lee J, Guo Z, Mattson MP: Dietary restriction stimulates BDNF production in the brain and thereby protects neurons against excitotoxic injury. J Mol Neurosci 2001;16:1-12.
24.
Krabbe KS, Nielsen AR, Krogh-Madsen R, Plomgaard P, Rasmussen P, Erikstrup C, et al: Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia 2007;50:431-438.
25.
Suwa M, Kishimoto H, Nofuji Y, Nakano H, Sasaki H, Radak Z, et al: Serum brain-derived neurotrophic factor level is increased and associated with obesity in newly diagnosed female patients with type 2 diabetes mellitus. Metabolism 2006;55:852-857.
26.
Teillon S, Calderon GA, Rios M: Diminished diet induced hyperglycemia and dyslipidemia and enhanced expression of PPARα and FGF21 in mice with hepatic ablation of brain-derived neurotropic factor. J Endocrinol 2010;205:37-47.
27.
Han X, Luo Y, Zhang X, Lv C, Sun X, Zhang X, et al: rs4074134 near BDNF gene is associated with type 2 diabetes mellitus in Chinese Han population independently of body mass index. PLoS One 2013;8:e56898.
28.
Zhang Y, Chen M, Wu Z, Chen J, Yu S, Fang Y, et al: Association study of Val66Met polymorphism in brain-derived neurotrophic factor gene with clozapine-induced metabolic syndrome: preliminary report. PLoS One 2013;8:e72652.
29.
Delahanty LM, Pan Q, Jablonski KA, Watson KE, McCaffery JM, Shuldiner A, et al: Genetic predictors of weight loss and weight regain after intensive lifestyle modification, metformin treatment, or standard care in the Diabetes Prevention Program. Diabetes Care 2012;35:363-366.
30.
Genzer Y, Dadon M, Burg C, Chapnik N, Froy O: Effect of dietary fat and the circadian clock on the expression of brain-derived neurotrophic factor (BDNF). Mol Cell Endocrinol 2016;430:49-55.
31.
McCaffery JM, Jablonski KA, Franks PW, Delahanty LM, Aroda V, Marrero D, et al: Replication of the association of BDNF and MC4R variants with dietary intake in the Diabetes Prevention Program. Psychosom Med 2017;79:224-233.
32.
Chung YC, Cui Y, Sumiyoshi T, Kim MG, Lee KH: Associations of fatty acids with cognition, psychopathology, and brain-derived neurotrophic factor levels in patients with first-episode schizophrenia and related disorders treated with paliperidone extended release. J Psychopharmacol 2017;31:1556-1563.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.