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Preliminary findings on the influence of FTO rs9939609 and MC4R rs17782313 polymorphisms on resting energy expenditure, leptin and thyrotropin levels in obese non-morbid premenopausal women

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Abstract

Given that leptin, ghrelin and thyrotropin play a major role in the regulation of resting energy expenditure (REE) and that the FTO rs9939609 and the MC4R rs17782313 polymorphisms have been proposed to affect energy homeostasis, we hypothesized that both polymorphisms are associated with REE and that these relationships can be mediated by leptin, ghrelin and thyrotropin in obesity. Therefore, the present study aimed to examine the relationships between FTO rs9939609 and the MC4R rs17782313 with REE, leptin, ghrelin and thyrotropin levels in obese women. The study comprised 77 obese (body mass index 34.0 ± 2.8 kg/m2) women (age 36.7 ± 7 years). We measured body composition by dual-energy X-ray absorptiometry and REE by indirect calorimetry. We analysed fasting leptin, ghrelin and thyrotropin levels and the ratio of leptin to fat mass was calculated. Genotype distributions of the polymorphisms did not deviate from Hardy–Weinberg expectations (P values >0.2). Women carrying the A allele of the FTO rs9939609 had lower REE (1,580 ± 22 vs. 1,739 ± 35 kcal/day, P < 0.001) and higher leptin to fat mass ratio (1.33 ± 0.05 vs. 1.13 ± 0.08 ng/ml kg, P < 0.05) and thyrotropin levels (1.93 ± 0.10 vs. 1.53 ± 0.16 μU/ml, P < 0.05) regardless of age and body mass index. We found no significant influence of the MC4R rs17782313 on energy metabolism or biochemical variables. Our findings confirm that the A allele of the FTO rs9939609 is associated with lower REE and increased plasma leptin levels. We also found an association between the FTO rs9939609 and thyrotropin, suggesting the possible influence of FTO in the hypothalamic–pituitary–thyroid axis as a potential mechanism of the increased adiposity.

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References

  1. al-Adsani H, Hoffer LJ, Silva JE (1997) Resting energy expenditure is sensitive to small dose changes in patients on chronic thyroid hormone replacement. J Clin Endocrinol Metab 82:1118–1125

    CAS  PubMed  Google Scholar 

  2. Andreasen CH, Stender-Petersen KL, Mogensen MS, Torekov SS, Wegner L, Andersen G et al (2008) Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 57:95–101

    Article  CAS  PubMed  Google Scholar 

  3. Berentzen T, Kring SI, Holst C, Zimmermann E, Jess T, Hansen T, Pedersen O, Toubro S, Astrup A, Sørensen TI (2008) Lack of association of fatness-related FTO gene variants with energy expenditure or physical activity. J Clin Endocrinol Metab 93:2904–2908

    Article  CAS  PubMed  Google Scholar 

  4. Biondi B (2010) Thyroid and obesity: an intriguing relationship. In J Clin Endocrinol Metab 95:3614–3617

    Article  CAS  Google Scholar 

  5. Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN (2008) An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med 359:2558–2566

    Article  CAS  PubMed  Google Scholar 

  6. Cole SA, Butte NF, Voruganti VS, Cai G, Haack K, Kent JW Jr, Blangero J, Comuzzie AG, McPherson JD, Gibbs RA (2010) Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic children. Am J Clin Nutr 91:191–199

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Compher C, Frankenfield D, Keim N, Roth-Yousey L (2006) Best practice methods to apply to measurement of resting metabolic rate in adults: a systematic review. J Am Diet Assoc 106:881–903

    Article  PubMed  Google Scholar 

  8. Cooper JA, Watras AC, O’Brien MJ, Luke A, Dobratz JR, Earthman CP, Schoeller DA (2009) Assessing validity and reliability of resting metabolic rate in six gas analysis systems. J Am Diet Assoc 109:128–132

    Article  PubMed Central  PubMed  Google Scholar 

  9. Do R, Bailey SD, Desbiens K, Belisle A, Montpetit A, Bouchard C, Pérusse L, Vohl MC, Engert JC (2008) Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec family study. Diabetes 57:1147–1150

    Article  CAS  PubMed  Google Scholar 

  10. Doucet E, St Pierre S, Alméras N, Mauriège P, Richard D, Tremblay A (2000) Changes in energy expenditure and substrate oxidation resulting from weight loss in obese men and women: is there an important contribution of leptin? J Clin Endocrinol Metab 85:1550–1556

    CAS  PubMed  Google Scholar 

  11. Dougkas A, Yaqoob P, Givens DI, Reynolds CK, Minihane AM (2013) The impact of obesity-related SNP on appetite and energy intake. Br J Nutr 22:1–6

    Google Scholar 

  12. Dwivedi OP, Tabassum R, Chauhan G, Ghosh S, Marwaha RK, Tandon N, Bharadwaj D (2012) Common variants of FTO are associated with childhood obesity in a cross-sectional study of 3,126 urban Indian children. PLoS One 7:e47772

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Fang H, Li Y, Du S, Hu X, Zhang Q, Liu A, Ma G (2010) Variant rs9939609 in the FTO gene is associated with body mass index among Chinese children. BMC Med Genet 11:136

    Article  PubMed Central  PubMed  Google Scholar 

  14. Feldt-Rasmussen U (2007) Thyroid and leptin. Thyroid 17:413–419

    Article  CAS  PubMed  Google Scholar 

  15. Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Brüning JC, Rüther U (2009) Inactivation of the Fto gene protects from obesity. Nature 458:894–898

    Article  CAS  PubMed  Google Scholar 

  16. Frayling TM, Timpson NJ, Weedon MN et al (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889–894

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Gil-Campos M, Aguilera CM, Cañete R, Gil A (2006) Ghrelin: a hormone regulating food intake and energy homeostasis. Br J Nutr 96:201–226

    Article  CAS  PubMed  Google Scholar 

  18. Hakanen M, Raitakari OT, Lehtimäki T, Peltonen N, Pahkala K, Sillanmäki L, Lagström H, Viikari J, Simell O, Rönnemaa T (2009) FTO genotype is associated with body mass index after the age of seven years but not with energy intake or leisure-time physical activity. J Clin Endocrinol Metab 94:1281–1287

    Article  CAS  PubMed  Google Scholar 

  19. Haupt A, Thamer C, Staiger H, Tschritter O, Kirchhoff K, Machicao F, Häring HU, Stefan N, Fritsche A (2009) Variation in the FTO gene influences food intake but not energy expenditure. Exp Clin Endocrinol Diabetes 117:194–197

    Article  CAS  PubMed  Google Scholar 

  20. Knudsen N, Laurberg P, Rasmussen LB, Bülow I, Perrild H, Ovesen L, Jørgensen T (2005) Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab 90:4019–4024

    Article  CAS  PubMed  Google Scholar 

  21. Krakoff J, Ma L, Kobes S, Knowler WC, Hanson RL, Bogardus C, Baier LJ (2008) Lower metabolic rate in individuals heterozygous for either a frameshift or a functional missense MC4R variant. Diabetes 57:3267–3272

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Kring SI, Holst C, Toubro S, Astrup A, Hansen T, Pedersen O, Sørensen TI (2010) Common variants near MC4R in relation to body fat, body fat distribution, metabolic traits and energy expenditure. Int J Obes (Lond) 34:182–189

    Article  CAS  Google Scholar 

  23. Labayen I, Díez N, González A, Parra D, Martínez JA (2003) Effects of protein vs. carbohydrate-rich diets on fuel utilisation in obese women during weight loss. Forum Nutr 56:168–170

    CAS  PubMed  Google Scholar 

  24. Labayen I, Díez N, Parra D, González A, Martínez JA (2004) Basal and postprandial substrate oxidation rates in obese women receiving two test meals with different protein content. Clin Nutr 23:571–578

    Article  CAS  PubMed  Google Scholar 

  25. Labayen I, Forga L, Martinez JA (1999) Nutrient oxidation and metabolic rate as affected by meals containing different proportions of carbohydrate and fat, in healthy young women. Eur J Nutr 38:158–166

    Article  CAS  PubMed  Google Scholar 

  26. Labayen I, Ortega FB, Ruiz JR, Lasa A, Simón E, Margareto J (2011) Role of baseline leptin and ghrelin levels on body weight and fat mass changes after an energy-restricted diet intervention in obese women: effects on energy metabolism. J Cli Endocrinol Metab 96:E996–E1000

    Article  CAS  Google Scholar 

  27. Labayen I, Ruiz JR, Ortega FB, Dallongeville J, Jiménez-Pavón D, Castillo MJ, De Henauw S, González-Gross M, Bueno G, Molnar D, Kafatos A, Díaz LE, Meirhaeghe A, Moreno LA (2011) Association between the FTO rs9939609 polymorphism and leptin in European adolescents: a possible link with energy balance control. The HELENA study. Int J Obes 35:882–882

    Article  Google Scholar 

  28. Larder R, Cheung MK, Tung YC, Yeo GS, Coll AP (2011) Where to go with FTO? Trends Endocrinol Metab 22:53–59

    Article  CAS  PubMed  Google Scholar 

  29. Liu G, Zhu H, Lagou V, Gutin B, Stallmann-Jorgensen IS, Treiber FA, Dong Y, Snieder H (2010) FTO variant rs9939609 is associated with body mass index and waist circumference, but not with energy intake or physical activity in European- and African-American youth. BMC Med Genet 11:57

    Article  PubMed Central  PubMed  Google Scholar 

  30. Loos RJ, Lindgren CM, Li S, Wheeler E, Zhao JH, Prokopenko I et al (2008) Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet 40:768–775

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Mejía-Benítez A, Klünder-Klünder M, Yengo L, Meyre D, Aradillas C, Cruz E, Pérez-Luque E, Malacara JM, Garay ME, Peralta-Romero J, Flores-Huerta S, García-Mena J, Froguel P, Cruz M, Bonnefond A (2013) Analysis of the contribution of FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes to obesity in Mexican children. BMC Med Genet 14:21

    Article  PubMed Central  PubMed  Google Scholar 

  32. Nogueiras R, Tschop MH, Zigman JM (2008) Central nervous system regulation of energy metabolism: ghrelin versus leptin. Ann N Y Acad Sci 1126:14–19

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Olszewski PK, Fredriksson R, Eriksson JD, Mitra A, Radomska KJ, Gosnell BA, Solvang MN, Levine AS, Schiöth HB (2009) Hypothalamic FTO is associated with the regulation of energy intake not feeding reward. BMC Neurosci 10:129

    Article  PubMed Central  PubMed  Google Scholar 

  34. Qi L, Kang K, Zhang C, van Dam RM, Kraft P, Hunter D, Lee CH, Hu FB (2008) Fat mass-and obesity-associated (FTO) gene variant is associated with obesity: longitudinal analyses in two cohort studies and functional test. Diabetes 57:3145–3151

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Reinehr T (2010) Obesity and thyroid function. Mol Cell Endocrinol 316:165–171

    Article  CAS  PubMed  Google Scholar 

  36. Roef G, Lapauw B, Goemaere S, Zmierczak HG, Toye K, Kaufman JM, Taes Y (2012) Body composition and metabolic parameters are associated with variation in thyroid hormone levels among euthyroid young men. Eur J Endocrinol 167:719–726

    Article  CAS  PubMed  Google Scholar 

  37. Ruiz JR, Labayen I, Ortega FB, Legry V, Moreno LA, Dallongeville J, Martínez-Gómez D, Bokor S, Manios Y, Ciarapica D, Gottrand F, De Henauw S, Molnár D, Sjöström M, Meirhaeghe A (2010) Attenuation of the effect of the FTO rs9939609 polymorphism on total and central body fat by physical activity in adolescents: the HELENA study. Arch Pediatr Adolesc Med 164:328–333

    Article  PubMed  Google Scholar 

  38. Ruiz JR, Larrarte E, Margareto J, Ares R, Alkorta P, Labayen I (2011) Preliminary findings on the role of PLIN1 polymorphisms on body composition and energy metabolism response to energy restriction in obese women. Br J Nutr 106:486–490

    Article  CAS  PubMed  Google Scholar 

  39. Speakman JR, Rance KA, Johnstone AM (2008) Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity (Silver Spring) 16:1961–1965

    Article  CAS  Google Scholar 

  40. St-Pierre DH, Karelis AD, Cianflone K, Conus F, Mignault D, Rabasa-Lhoret R, St-Onge M, Tremblay-Lebeau A, Poehlman ET (2004) Relationship between ghrelin and energy expenditure in healthy young women. J Clin Endocrinol Metab 89:5993–5997

    Article  CAS  PubMed  Google Scholar 

  41. Tews D, Fischer-Posovszky P, Fromme T, Klingenspor M, Fischer J, Rüther U, Marienfeld R, Barth T, Möller P, Debatin K, Wabitsch M (2013) FTO deficiency induces UCP-1 expression and mitochondrial uncoupling in adipocytes. Endocrinology 154:3141–3151

    Article  CAS  PubMed  Google Scholar 

  42. Thearle MS, Muller YL, Hanson RL, Mullins M, Abdussamad M, Tran J, Knowler WC, Bogardus C, Krakoff J, Baier LJ (2012) Greater impact of melanocortin-4 receptor deficiency on rates of growth and risk of type 2 diabetes during childhood compared with adulthood in Pima Indians. Diabetes 61:250–257

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Xi B, Chandak GR, Shen Y, Wang Q, Zhou D (2012) Association between common polymorphism near the MC4R gene and obesity risk: a systematic review and meta-analysis. PLoS One 7:e45731

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

We thank the women for their participation in the study and Raquel Ares, Silvia Francisco, Izaskun Felipe and Emilio Sanz for their contribution to the participant’s recruitment and medical supervision of the study. This study was supported by the University of the Basque Country (UPV 05/80), Social Foundation of the Caja Vital-Kutxa and by the Department of Health of the Government of the Basque Country (2008/111062).

Compliance with ethics guidelines

The study was in accordance with the Helsinki II Declaration, as revised in 2000 and was approved by the Ethical Committee of the Hospital of Txagorritxu (Vitoria, Spain). All participants received verbal and written information about the nature and purpose of the study, and all of them gave written consent to participate.

Conflict of interest

Maria Arrizabalaga, Eider Larrarte, Javier Margareto, Sara Maldonado, Lourdes Barrenetxea and Idoia Labayen declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Nutrition and Food Science, University of the Basque Country, UPV/EHU, Paseo de la Universidad 7, 01006, Vitoria, Spain

    María Arrizabalaga & Idoia Labayen

  2. Health and Quality of Life Area, Tecnalia, Miñano, Spain

    Eider Larrarte

  3. Biomedical Research Area, Tecnalia, Miñano, Spain

    Javier Margareto

  4. Department of Physical Education and Sport, University of the Basque Country, UPV/EHU, Vitoria, Spain

    Sara Maldonado-Martín

  5. Department of Medicine, University of the Basque Country, UPV/EHU, Vitoria, Spain

    Lurdes Barrenechea

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  1. María Arrizabalaga
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  6. Idoia Labayen
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Correspondence to Idoia Labayen.

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Arrizabalaga, M., Larrarte, E., Margareto, J. et al. Preliminary findings on the influence of FTO rs9939609 and MC4R rs17782313 polymorphisms on resting energy expenditure, leptin and thyrotropin levels in obese non-morbid premenopausal women. J Physiol Biochem 70, 255–262 (2014). https://doi.org/10.1007/s13105-013-0300-5

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