Skip to main content
Log in

DNA Methylation and Hydroxymethylation Levels in Relation to Two Weight Loss Strategies: Energy-Restricted Diet or Bariatric Surgery

  • Original Contributions
  • Published:
Obesity Surgery Aims and scope Submit manuscript

Abstract

Background

Weight loss can be influenced by genetic factors and epigenetic mechanisms that participate in the regulation of body weight. This study aimed to investigate whether the weight loss induced by two different obesity treatments (energy restriction or bariatric surgery) may affect global DNA methylation (LINE-1) and hydroxymethylation profile, as well as the methylation patterns in inflammatory genes.

Methods

This study encompassed women from three differents groups: 1. control group (n = 9), normal weight individuals; 2. energy restriction group (n = 22), obese patients following an energy-restricted Mediterranean-based dietary treatment (RESMENA); and 3. bariatric surgery group (n = 14), obese patients underwent a hypocaloric diet followed by bariatric surgery. Anthropometric measurements and 12-h fasting blood samples were collected before the interventions and after 6 months. Lipid and glucose biomarkers, global hydroxymethylation (by ELISA), LINE-1, SERPINE-1, and IL-6 (by MS-HRM) methylation levels were assessed in all participants.

Results

Baseline LINE-1 methylation was associated with serum glucose levels whereas baseline hydroxymethylation was associated with BMI, waist circumference, total cholesterol, and triglycerides. LINE-1 and SERPINE-1 methylation levels did not change after weight loss, whereas IL-6 methylation increased after energy restriction and decreased in the bariatric surgery group. An association between SERPINE-1 methylation and weight loss responses was found.

Conclusions

Global DNA methylation and hydroxymethylation might be biomarkers for obesity and associated comorbidities. Depending on the obesity treatment (diet or surgery), the DNA methylation patterns behave differently. Baseline SERPINE-1 methylation may be a predictor of weight loss values after bariatric surgery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Organization WH. Global status report on noncommunicable diseases. In: Organization WH, editor. Rome, Italy; 2011.

  2. Martinez JA, Parra MD, Santos JL, et al. Genotype-dependent response to energy-restricted diets in obese subjects: towards personalized nutrition. Asia Pac J Clin Nutr. 2008;17 Suppl 1:119–22.

    PubMed  Google Scholar 

  3. Ara R, Blake L, Gray L, et al. What is the clinical effectiveness and cost-effectiveness of using drugs in treating obese patients in primary care? A systematic review. Health Technol Assess. 2012;16(5):iii–xiv. 1–195.

    Article  CAS  PubMed  Google Scholar 

  4. Sjostrom L. Review of the key results from the Swedish Obese Subjects (SOS) trial—a prospective controlled intervention study of bariatric surgery. J Intern Med. 2013;273(3):219–34.

    Article  CAS  PubMed  Google Scholar 

  5. Zulet MA, Bondia-Pons I, Abete I, et al. The reduction of the metabolyc syndrome in Navarra-Spain (RESMENA-S) study: a multidisciplinary strategy based on chrononutrition and nutritional education, together with dietetic and psychological control. Nutr Hosp. 2011;26(1):16–26.

    CAS  PubMed  Google Scholar 

  6. Lopez-Legarrea P, de la Iglesia R, Abete I, et al. The protein type within a hypocaloric diet affects obesity-related inflammation: the RESMENA project. Nutrition. 2014;30(4):424–9.

    Article  CAS  PubMed  Google Scholar 

  7. Wadden TA, Butryn ML, Byrne KJ. Efficacy of lifestyle modification for long-term weight control. Obes Res. 2004;12(Suppl):151S–62S.

    Article  PubMed  Google Scholar 

  8. Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2011. Obes Surg. 2013;23(4):427–36.

    Article  PubMed  Google Scholar 

  9. Neff KJ, le Roux CW. Bariatric surgery: a best practice article. J Clin Pathol. 2013;66(2):90–8.

    Article  PubMed  Google Scholar 

  10. Hainer V, Zamrazilova H, Spalova J, et al. Role of hereditary factors in weight loss and its maintenance. Physiol Res. 2008;57 Suppl 1:S1–S15.

    CAS  PubMed  Google Scholar 

  11. Still CD, Wood GC, Chu X, et al. High allelic burden of four obesity SNPs is associated with poorer weight loss outcomes following gastric bypass surgery. Obesity (Silver Spring). 2011;19(8):1676–83.

    Article  CAS  Google Scholar 

  12. Martinez JA, Milagro FI, Claycombe KJ, et al. Epigenetics in adipose tissue, obesity, weight loss, and diabetes. Adv Nutr. 2014;5(1):71–81.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Choi SW, Claycombe KJ, Martinez JA, et al. Nutritional epigenomics: a portal to disease prevention. Adv Nutr. 2013;4(5):530–2.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Milagro FI, Campion J, Cordero P, et al. A dual epigenomic approach for the search of obesity biomarkers: DNA methylation in relation to diet-induced weight loss. FASEB J. 2011;25(4):1378–89.

    Article  CAS  PubMed  Google Scholar 

  15. Moleres A, Campión J, Milagro FI, et al. Differential DNA methylation patterns between high and low responders to a weight loss intervention in overweight or obese adolescents: the EVASYON study. FASEB J. 2013;27(6):2504–12.

    Article  CAS  PubMed  Google Scholar 

  16. Bouchard L, Rabasa-Lhoret R, Faraj M, et al. Differential epigenomic and transcriptomic responses in subcutaneous adipose tissue between low and high responders to caloric restriction. Am J Clin Nutr. 2010;91(2):309–20.

    Article  CAS  PubMed  Google Scholar 

  17. Zhao J, Goldberg J, Vaccarino V. Promoter methylation of serotonin transporter gene is associated with obesity measures: a monozygotic twin study. Int J Obes (Lond). 2013;37(1):140–5.

    Article  CAS  Google Scholar 

  18. Campion J, Milagro FI, Martinez JA. Individuality and epigenetics in obesity. Obes Rev. 2009;10(4):383–92.

    Article  CAS  PubMed  Google Scholar 

  19. Barres R, Kirchner H, Rasmussen M, et al. Weight loss after gastric bypass surgery in human obesity remodels promoter methylation. Cell Rep. 2013;3(4):1020–7.

    Article  CAS  PubMed  Google Scholar 

  20. Kirchner H, Nylen C, Laber S, et al. Altered promoter methylation of PDK4, IL1 B, IL6, and TNF after Roux-en Y gastric bypass. Surg Obes Relat Dis. 2014;10(4):671–8.

    Article  PubMed  Google Scholar 

  21. Weisenberger DJ, Campan M, Long TI, et al. Analysis of repetitive element DNA methylation by MethyLight. Nucleic Acids Res. 2005;33(21):6823–36.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Feinberg AP, Irizarry RA, Fradin D, et al. Personalized epigenomic signatures that are stable over time and covary with body mass index. Sci Transl Med. 2010;2(49):49ra67.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Zhu ZZ, Hou L, Bollati V, et al. Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis. Int J Epidemiol. 2012;41(1):126–39.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Perng W, Mora-Plazas M, Marin C, et al. A prospective study of LINE-1DNA methylation and development of adiposity in school-age children. PLoS One. 2013;8(4), e62587.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Zhao J, Goldberg J, Bremner JD, et al. Global DNA methylation is associated with insulin resistance: a monozygotic twin study. Diabetes. 2012;61(2):542–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Martin-Nunez GM, Cabrera-Mulero R, Rubio-Martin E, et al. Methylation levels of the SCD1 gene promoter and LINE-1 repeat region are associated with weight change: an intervention study. Mol Nutr Food Res. 2014;58(7):1528–36.

    Article  CAS  PubMed  Google Scholar 

  27. Cash HL, McGarvey ST, Houseman EA, et al. Cardiovascular disease risk factors and DNA methylation at the LINE-1 repeat region in peripheral blood from Samoan Islanders. Epigenetics. 2011;6(10):1257–64.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Crow MK. Long interspersed nuclear elements (LINE-1): potential triggers of systemic autoimmune disease. Autoimmunity. 2010;43(1):7–16.

    Article  CAS  PubMed  Google Scholar 

  29. Lopez-Legarrea P, Mansego ML, Zulet MA, et al. SERPINE1, PAI-1 protein coding gene, methylation levels and epigenetic relationships with adiposity changes in obese subjects with metabolic syndrome features under dietary restriction. J Clin Biochem Nutr. 2013;53(3):139–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Pfeifer GP, Kadam S, Jin SG. 5-hydroxymethylcytosine and its potential roles in development and cancer. Epigenetics Chromatin. 2013;6(1):10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. de la Iglesia R, Lopez-Legarrea P, Abete I, et al. A new dietary strategy for long-term treatment of the metabolic syndrome is compared with the American Heart Association (AHA) guidelines: the MEtabolic Syndrome REduction in NAvarra (RESMENA) project. Br J Nutr. 2014;111(4):643–52.

    Article  PubMed  Google Scholar 

  32. Perez-Cornago A, Lopez-Legarrea P, de la Iglesia R, et al. Longitudinal relationship of diet and oxidative stress with depressive symptoms in patients with metabolic syndrome after following a weight loss treatment: the RESMENA project. Clin Nutr. 2014;33(6):1061–7.

    Article  CAS  PubMed  Google Scholar 

  33. Perez-Cornago A, de la Iglesia R, Lopez-Legarrea P, et al. A decline in inflammation is associated with less depressive symptoms after a dietary intervention in metabolic syndrome patients: a longitudinal study. Nutr J. 2014;13:36.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Bavaresco M, Paganini S, Lima TP, et al. Nutritional course of patients submitted to bariatric surgery. Obes Surg. 2010;20(6):716–21.

    Article  PubMed  Google Scholar 

  35. Nicoletti CF, de Oliveira BA, de Pinhel MA, et al. Influence of excess weight loss and weight regain on biochemical indicators during a 4-year follow-up after Roux-en-Y gastric bypass. Obes Surg. 2015;25(2):279–84.

    Article  PubMed  Google Scholar 

  36. Biro SM, Olson DL, Garren MJ, et al. Diabetes remission and glycemic response to pre-bariatric surgery diet. J Surg Res. 2013;185(1):1–5.

    Article  PubMed  Google Scholar 

  37. Fraga MF, Ballestar E, Paz MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A. 2005;102(30):10604–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Bjornsson HT, Sigurdsson MI, Fallin MD, et al. Intra-individual change over time in DNA methylation with familial clustering. JAMA. 2008;299(24):2877–83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Zhang FF, Santella RM, Wolff M, et al. White blood cell global methylation and IL-6 promoter methylation in association with diet and lifestyle risk factors in a cancer-free population. Epigenetics. 2012;7(6):606–14.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Huang YT, Maccani JZ, Hawley NL, Wing RR, Kelsey KT, McCaffery JM. Epigenetic patterns in successful weight loss maintainers: a pilot study. Int J Obes (Lond). 2014.

  41. Pearce MS, McConnell JC, Potter C, et al. Global LINE-1 DNA methylation is associated with blood glycaemic and lipid profiles. Int J Epidemiol. 2012;41(1):210–7.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Ulrich CM, Toriola AT, Koepl LM, et al. Metabolic, hormonal and immunological associations with global DNA methylation among postmenopausal women. Epigenetics. 2012;7(9):1020–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Shen L, Wu H, Diep D, et al. Genome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics. Cell. 2013;153(3):692–706.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Gao F, Das SK. Epigenetic regulations through DNA methylation and hydroxymethylation: clues for early pregnancy in decidualization. Biomol Concepts. 2014;5(2):95–107.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Song CX, Szulwach KE, Dai Q, et al. Genome-wide profiling of 5-formylcytosine reveals its roles in epigenetic priming. Cell. 2013;153(3):678–91.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Branco MR, Ficz G, Reik W. Uncovering the role of 5‐hydroxymethylcytosine in the epigenome. Nat Rev Genet. 2012;13:7–13.

    CAS  Google Scholar 

  47. Valinluck V, Tsai HH, Rogstad DK, et al. Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). Nucleic Acids Res. 2004;32(14):4100–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Guibert S, Weber M. Functions of DNA methylation and hydroxymethylation in mammalian development. Curr Top Dev Biol. 2013;104:47–83.

    Article  CAS  PubMed  Google Scholar 

  49. Lister R, Mukamel EA, Nery JR, et al. Global epigenomic reconfiguration during mammalian brain development. Science. 2013;341(6146):1237905.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Lashley T, Gami P, Valizadeh N, Li A, Revesz T, Balazs R. Alterations in global DNA methylation and hydroxymethylation are not detected in Alzheimer’s disease. Neuropathol Appl Neurobiol. 2014.

  51. Coppieters N, Dieriks BV, Lill C, et al. Global changes in DNA methylation and hydroxymethylation in Alzheimer’s disease human brain. Neurobiol Aging. 2014;35(6):1334–44.

    Article  CAS  PubMed  Google Scholar 

  52. Nathan DM, Davidson MB, DeFronzo RA, et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care. 2007;30(3):753–9.

    Article  CAS  PubMed  Google Scholar 

  53. Tonet AC, Karnikowski M, Moraes CF, et al. Association between the -174 G/C promoter polymorphism of the interleukin-6 gene and cardiovascular disease risk factors in Brazilian older women. Braz J Med Biol Res. 2008;41(1):47–53.

    Article  CAS  PubMed  Google Scholar 

  54. Moleres A, Rendo-Urteaga T, Azcona C, et al. Il6 gene promoter polymorphism (-174G/C) influences the association between fat mass and cardiovascular risk factors. J Physiol Biochem. 2009;65(4):405–13.

    Article  CAS  PubMed  Google Scholar 

  55. Roth CL, Kratz M, Ralston MM, et al. Changes in adipose-derived inflammatory cytokines and chemokines after successful lifestyle intervention in obese children. Metabolism. 2011;60(4):445–52.

    Article  CAS  PubMed  Google Scholar 

  56. Bocca G, Corpeleijn E, Stolk RP, et al. Effect of obesity intervention programs on adipokines, insulin resistance, lipid profile, and low-grade inflammation in 3- to 5-y-old children. Pediatr Res. 2014;75(2):352–7.

    Article  CAS  PubMed  Google Scholar 

  57. Campion J, Milagro F, Martinez JA. Epigenetics and obesity. Prog Mol Biol Transl Sci. 2010;94:291–347.

    Article  CAS  PubMed  Google Scholar 

  58. Kohler HP, Grant PJ. Plasminogen-activator inhibitor type 1 and coronary artery disease. N Engl J Med. 2000;342(24):1792–801.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Verónica Ciáurriz for the technical assistant. This work was supported by grant no. 2014/04902-1 and no. 2013/08916-4 from the São Paulo Research Foundation (FAPESP), Brazil; the Spanish Government (CIBERobn Network and the Nutrigenio project, ref. AGL2013-45554-R); and the Government of Navarra (RESMENA project; ref. 48/2009) and IdiSNA, Navarra Institute for Health Research.

Conflict of Interest

The authors declare that they have no competing interests.

Statement of Informed Consent (When Reporting Studies That Involve Human Participants)

Informed consent was obtained from all individual participants included in the study.

Statement of Human and Animal Rights

This research was approved by the appropriate Ethical Committes in Spain and Brazil. Also, the updated guidelines of the Helsinki declaration and EU regulations were strictly followed.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to José Alfredo Martinez.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nicoletti, C.F., Nonino, C.B., de Oliveira, B.A.P. et al. DNA Methylation and Hydroxymethylation Levels in Relation to Two Weight Loss Strategies: Energy-Restricted Diet or Bariatric Surgery. OBES SURG 26, 603–611 (2016). https://doi.org/10.1007/s11695-015-1802-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11695-015-1802-8

Keywords

Navigation