Background/Aims: Investigation of the genetic makeup may facilitate the implementation of more personalized nutritional interventions. The aims were to examine whether the rs10830963 MTNR1B polymorphism affects weight loss in response to a hypocaloric diet and to find potential gene-gene interplays and gene-diet interactions. Methods: 167 subjects enrolled in a personalized nutritional intervention for weight loss (3-6 weeks) were examined for anthropometric measurements, dietary habits and physical activity at baseline and at the first follow-up visit. Three polymorphisms, which have previously been associated with body weight regulation, rs10830963 (MTNR1B), rs9939609 (FTO) and rs17782313 (MC4R), were analyzed using the Luminex® 100/200™ System. Results: After adjusting for covariates, females with the rs10830963 CG/GG genotype showed lower weight loss than those with the CC genotype. In the total population, carriers of variant alleles of both FTO and MC4R showed a significant association with MTNR1B and weight loss outcome. Moreover, among women, higher total protein and animal protein intakes were associated with a lower weight loss in G allele carriers of the MTNR1B variant. Conclusions: Our data evidenced that rs10830963 MTNR1B polymorphism could be associated with individual differences in weight loss induced by a hypocaloric diet. This association was influenced by FTO and MC4R loci and modified by baseline protein intake.

1.
Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al: Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the global burden of disease study 2013. Lancet 2014;384:766-781.
2.
Kushner RF: Weight loss strategies for treatment of obesity. Prog Cardiovasc Dis 2014;56:465-472.
3.
Abete I, Astrup A, Martinez JA, Thorsdottir I, Zulet MA: Obesity and the metabolic syndrome: role of different dietary macronutrient distribution patterns and specific nutritional components on weight loss and maintenance. Nutr Rev 2010;68:214-231.
4.
Perez-Cornago A, Ramirez MJ, Zulet MA, Martinez JA: Effect of dietary restriction on peripheral monoamines and anxiety symptoms in obese subjects with metabolic syndrome. Psychoneuroendocrinology 2014;47:98-106.
5.
Burmeister JM, Carels RA: Television use and binge eating in adults seeking weight loss treatment. Eat Behav 2014;15:83-86.
6.
Mariman EC: Human biology of weight maintenance after weight loss. J Nutrigenet Nutrigenomics 2012;5:13-25.
7.
Moreno-Aliaga MJ, Santos JL, Marti A, Martinez JA: Does weight loss prognosis depend on genetic make-up? Obes Rev 2005;6:155-168.
8.
Deram S, Villares SM: Genetic variants influencing effectiveness of weight loss strategies. Arq Bras Endocrinol Metab 2009;53:129-138.
9.
Goni L, Milagro FI, Cuervo M, Martinez JA: Single-nucleotide polymorphisms and DNA methylation markers associated with central obesity and regulation of body weight. Nutr Rev 2014;72:673-690.
10.
Gomez-Abellan P, Madrid JA, Ordovas JM, Garaulet M: Chronobiological aspects of obesity and metabolic syndrome. Endocrinol Nutr 2012;59:50-61.
11.
Summa KC, Turek FW: Chronobiology and obesity: interactions between circadian rhythms and energy regulation. Adv Nutr 2014;5:312S-319S.
12.
Barrenetxe J, Delagrange P, Martinez JA: Physiological and metabolic functions of melatonin. J Physiol Biochem 2004;60:61-72.
13.
Cipolla-Neto J, Amaral FG, Afeche SC, Tan DX, Reiter RJ: Melatonin, energy metabolism, and obesity: a review. J Pineal Res 2014;56:371-381.
14.
Stančáková A, Kuulasmaa T, Paananen J, Jackson AU, Bonnycastle LL, Collins FS, Boehnke M, Kuusisto J, Laakso M: Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5,327 nondiabetic Finnish men. Diabetes 2009;58:2129-2136.
15.
Andersson EA, Holst B, Sparso T, Grarup N, Banasik K, Holmkvist J, Jorgensen T, Borch-Johnsen K, Egerod KL, Lauritzen T, Sorensen TI, Bonnefond A, Meyre D, Froguel P, Schwartz TW, Pedersen O, Hansen T: MTNR1B G24E variant associates with BMI and fasting plasma glucose in the general population in studies of 22,142 Europeans. Diabetes 2010;59:1539-1548.
16.
Peter I, McCaffery JM, Kelley-Hedgepeth A, Hakonarson H, Reis S, Wagenknecht LE, Kopin AS, Huggins GS; Genetics Subgroup of the Look AHEAD Study: Association of type 2 diabetes susceptibility loci with one-year weight loss in the Look AHEAD clinical trial. Obesity (Silver Spring) 2012;20:1675-1682.
17.
Mirzaei K, Xu M, Qi Q, de Jonge L, Bray GA, Sacks F, Qi L: Variants in glucose- and circadian rhythm-related genes affect the response of energy expenditure to weight-loss diets: the POUNDS LOST Trial. Am J Clin Nutr 2014;99:392-399.
18.
Mulder H, Nagorny CL, Lyssenko V, Groop L: Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene. Diabetologia 2009;52:1240-1249.
19.
Zhang C, Bao W, Rong Y, Yang H, Bowers K, Yeung E, Kiely M: Genetic variants and the risk of gestational diabetes mellitus: a systematic review. Hum Reprod Update 2013;19:376-390.
20.
de Luis DA, Aller R, Conde R, Izaola O, Gonzalez Sagrado M, Castrodeza Sanz J: The rs9939609 gene variant in FTO modified the metabolic response of weight loss after a 3-month intervention with a hypocaloric diet. J Investig Med 2013;61:22-26.
21.
Zlatohlavek L, Vrablik M, Motykova E, Ceska R, Vasickova L, Dlouha D, Hubacek JA: FTO and MC4R gene variants determine BMI changes in children after intensive lifestyle intervention. Clin Biochem 2013;46:313-316.
22.
Goni L, Cuervo M, Milagro FI, Martinez JA: A genetic risk tool for obesity predisposition assessment and personalized nutrition implementation based on macronutrient intake. Genes Nutr 2015;10:445.
23.
Panel on Macronutrients, Panel on the Definition of Dietary Fiber, Subcommittee on Upper Reference Levels of Nutrients, Subcommittee on Interpretation and Uses of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes: Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). Washington, The National Academies Press, 2005.
24.
Mataix J: Tablas de composición de alimentos, ed 5. Granada, EUG, 2009.
25.
Moreiras O: Tablas de composición de alimentos, ed 15. Madrid, Pirámide, 2012.
26.
Dunbar SA: Applications of Luminex xMAP technology for rapid, high-throughput multiplexed nucleic acid detection. Clin Chim Acta 2006;363:71-82.
27.
Holzapfel C, Siegrist M, Rank M, Langhof H, Grallert H, Baumert J, Irimie C, Klopp N, Wolfarth B, Illig T, Hauner H, Halle M: Association of a MTNR1B gene variant with fasting glucose and HOMA-B in children and adolescents with high BMI-SDS. Eur J Endocrinol 2011;164:205-212.
28.
Sparso T, Bonnefond A, Andersson E, Bouatia-Naji N, Holmkvist J, Wegner L, Grarup N, Gjesing AP, Banasik K, Cavalcanti-Proenca C, Marchand M, Vaxillaire M, Charpentier G, Jarvelin MR, Tichet J, Balkau B, Marre M, Levy-Marchal C, Faerch K, Borch-Johnsen K, Jorgensen T, Madsbad S, Poulsen P, Vaag A, Dina C, Hansen T, Pedersen O, Froguel P: G-allele of intronic rs10830963 in MTNR1B confers increased risk of impaired fasting glycemia and type 2 diabetes through an impaired glucose-stimulated insulin release: studies involving 19,605 Europeans. Diabetes 2009;58:1450-1456.
29.
Srinivasan V, Ohta Y, Espino J, Pariente JA, Rodriguez AB, Mohamed M, Zakaria R: Metabolic syndrome, its pathophysiology and the role of melatonin. Recent Pat Endocr Metab Immune Drug Discov 2013;7:11-25.
30.
Lyssenko V, Nagorny CL, Erdos MR, Wierup N, Jonsson A, Spegel P, Bugliani M, Saxena R, Fex M, Pulizzi N, Isomaa B, Tuomi T, Nilsson P, Kuusisto J, Tuomilehto J, Boehnke M, Altshuler D, Sundler F, Eriksson JG, Jackson AU, Laakso M, Marchetti P, Watanabe RM, Mulder H, Groop L: Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nat Genet 2009;41:82-88.
31.
Xia Q, Chen ZX, Wang YC, Ma YS, Zhang F, Che W, Fu D, Wang XF: Association between the melatonin receptor 1B gene polymorphism on the risk of type 2 diabetes, impaired glucose regulation: a meta-analysis. PLoS One 2012;7:e50107.
32.
Ochner CN, Barrios DM, Lee CD, Pi-Sunyer FX: Biological mechanisms that promote weight regain following weight loss in obese humans. Physiol Behav 2013;120:106-113.
33.
van Nas A, Guhathakurta D, Wang SS, Yehya N, Horvath S, Zhang B, Ingram-Drake L, Chaudhuri G, Schadt EE, Drake TA, Arnold AP, Lusis AJ: Elucidating the role of gonadal hormones in sexually dimorphic gene coexpression networks. Endocrinology 2009;150:1235-1249.
34.
Dempfle A, Hinney A, Heinzel-Gutenbrunner M, Raab M, Geller F, Gudermann T, Schafer H, Hebebrand J: Large quantitative effect of melanocortin-4 receptor gene mutations on body mass index. J Med Genet 2004;41:795-800.
35.
Lindgren CM, Heid IM, Randall JC, Lamina C, Steinthorsdottir V, Qi L, et al: Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. PLoS Genet 2009;5:e1000508.
36.
Heid IM, Jackson AU, Randall JC, Winkler TW, Qi L, Steinthorsdottir V, et al: Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet 2010;42:949-960.
37.
Randall JC, Winkler TW, Kutalik Z, Berndt SI, Jackson AU, Monda KL, et al: Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits. PLoS Genet 2013;9:e1003500.
38.
Navas-Carretero S, Holst C, Saris W, van Baak M, Jebb S, Kafatos A, Papadaki A, Pfeiffer A, Handjieva-Darlenska T, Hlavaty P, Stender S, Larsen T, Astrup A, Martinez J: Gender and protein intake impact on the success of weight maintenance and cardiovascular risk benefits, independently of the mode of food provision: the DiOGenes randomised trial. J Am Coll Nutr, in press.
39.
Loos RJ, Yeo GS: The bigger picture of FTO: the first GWAS-identified obesity gene. Nat Rev Endocrinol 2014;10:51-61.
40.
Villalobos-Comparan M, Teresa Flores-Dorantes M, Teresa Villarreal-Molina M, Rodriguez-Cruz M, Garcia-Ulloa AC, Robles L, Huertas-Vazquez A, Saucedo-Villarreal N, Lopez-Alarcon M, Sanchez-Munoz F, Dominguez-Lopez A, Gutierrez-Aguilar R, Menjivar M, Coral-Vazquez R, Hernandez-Stengele G, Vital-Reyes VS, Acuna-Alonzo V, Romero-Hidalgo S, Ruiz-Gomez DG, Riano-Barros D, Herrera MF, Gomez-Perez FJ, Froguel P, Garcia-Garcia E, Teresa Tusie-Luna M, Aguilar-Salinas CA, Canizales-Quinteros S: The FTO gene is associated with adulthood obesity in the Mexican population. Obesity (Silver Spring) 2008;16:2296-2301.
41.
Lappalainen T, Kolehmainen M, Schwab U, Pulkkinen L, de Mello VD, Vaittinen M, Laaksonen DE, Poutanen K, Uusitupa M, Gylling H: Gene expression of FTO in human subcutaneous adipose tissue, peripheral blood mononuclear cells and adipocyte cell line. J Nutrigenet Nutrigenomics 2010;3:37-45.
42.
Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gomez-Marin C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF, Lee JH, Puviindran V, Tam D, Shen M, Son JE, Vakili NA, Sung HK, Naranjo S, Acemel RD, Manzanares M, Nagy A, Cox NJ, Hui CC, Gomez-Skarmeta JL, Nobrega MA: Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 2014;507:371-375.
43.
Loos RJ: The genetic epidemiology of melanocortin 4 receptor variants. Eur J Pharmacol 2011;660:156-164.
44.
Hinney A, Volckmar AL, Knoll N: Melanocortin-4 receptor in energy homeostasis and obesity pathogenesis. Prog Mol Biol Transl Sci 2013;114:147-191.
45.
El-Sayed Moustafa JS, Froguel P: From obesity genetics to the future of personalized obesity therapy. Nat Rev Endocrinol 2013;9:402-413.
46.
Zhang X, Qi Q, Zhang C, Smith SR, Hu FB, Sacks FM, Bray GA, Qi L: FTO genotype and 2-year change in body composition and fat distribution in response to weight-loss diets: the POUNDS LOST Trial. Diabetes 2012;61:3005-3011.
47.
Verhoef SP, Camps SG, Bouwman FG, Mariman EC, Westerterp KR: Genetic predisposition, dietary restraint and disinhibition in relation to short and long-term weight loss. Physiol Behav 2014;128:247-251.
48.
Qi L: Gene-diet interaction and weight loss. Curr Opin Lipidol 2014;25:27-34.
49.
Martinez JA, Navas-Carretero S, Saris WH, Astrup A: Personalized weight loss strategies - the role of macronutrient distribution. Nat Rev Endocrinol 2014;10:749-760.
50.
Oishi K, Uchida D, Itoh N: Low-carbohydrate, high-protein diet affects rhythmic expression of gluconeogenic regulatory and circadian clock genes in mouse peripheral tissues. Chronobiol Int 2012;29:799-809.
51.
Teixeira PJ, Going SB, Houtkooper LB, Cussler EC, Metcalfe LL, Blew RM, Sardinha LB, Lohman TG: Pretreatment predictors of attrition and successful weight management in women. Int J Obes Relat Metab Disord 2004;28:1124-1133.
52.
Westerterp-Plantenga MS, Nieuwenhuizen A, Tome D, Soenen S, Westerterp KR: Dietary protein, weight loss, and weight maintenance. Annu Rev Nutr 2009;29:21-41.
53.
Ortner Hadziabdic M, Mucalo I, Hrabac P, Matic T, Rahelic D, Bozikov V: Factors predictive of drop-out and weight loss success in weight management of obese patients. J Hum Nutr Diet 2015;28(suppl 2):24-32.
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.