A systematic review of studies of DNA methylation in the context of a weight loss intervention

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

• 1 World Health Organisation. www.who.int/mediacentre/factsheets/fs311/en/
  Google Scholar
• 2 Pi-Sunyer X. The medical risks of obesity. Postgrad. Med. 121(6), 21–33 (2009).
  MedlineGoogle Scholar
• 3 Wang YC, Mcpherson K, Marsh T, Gortmaker SL, Brown M. Health and economic burden of the projected obesity trends in the USA and the UK. Lancet 378(9793), 815–825 (2011).
  MedlineGoogle Scholar
• 4 Misra A, Singhal N, Khurana L. Obesity, the metabolic syndrome, and Type 2 diabetes in developing countries: role of dietary fats and oils. J. Am. Coll. Nutr. 29(3 Suppl.), s289–s301 (2010).
  Google Scholar
• 5 Bouchard C. Gene-environment interactions in the etiology of obesity: defining the fundamentals. Obesity 16(Suppl. 3), S5–S10 (2008).
  Medline CASGoogle Scholar
• 6 Yang J, Bakshi A, Zhu Z et al. Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index. Nat. Genet. 47(10), 1114–1120 (2015).
  Medline CASGoogle Scholar
• 7 Llewellyn CH, Trzaskowski M, Plomin R, Wardle J. Finding the missing heritability in pediatric obesity: the contribution of genome-wide complex trait analysis. Int. J. Obes. (Lond.) 37(11), 1506–1509 (2013).
  CASGoogle Scholar
• 8 Elks CE, Den Hoed M, Zhao JH et al. Variability in the heritability of body mass index: a systematic review and meta-regression. Front. Endocrinol. 3, 29 (2012).
  MedlineGoogle Scholar
• 9 Fleisch AF, Wright RO, Baccarelli AA. Environmental epigenetics: a role in endocrine disease? J. Mol. Endocrinol. 49(2), R61–R67 (2012).
  Medline CASGoogle Scholar
• 10 De Carvalho DD, You JS, Jones PA. DNA methylation and cellular reprogramming. Trends Cell Biol. 20(10), 609–617 (2010).
  Medline CASGoogle Scholar
• 11 Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13(7), 484–492 (2012).
  Medline CASGoogle Scholar
• 12 Losko M, Kotlinowski J, Jura J. Long noncoding RNAs in metabolic syndrome related disorders. Mediators Inflamm. 2016, 5365209 (2016).
  MedlineGoogle Scholar
• 13 Feil R, Fraga MF. Epigenetics and the environment: emerging patterns and implications. Nat. Rev. Genet. 13(2), 97–109 (2012).
  Medline CASGoogle Scholar
• 14 Drummond EM, Gibney ER. Epigenetic regulation in obesity. Curr. Opin. Clin. Nutr. Metab. Care 16(4), 392–397 (2013).
  Medline CASGoogle Scholar
• 15 Wahl S, Drong A, Lehne B et al. Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity. Nature 541(7635), 81–86 (2017). •• The largest study to date of epigenome-wide global DNA methylation changes associated with obesity including a prospective analysis of the association between methylation changes and Type 2 diabetes risk.
  Medline CASGoogle Scholar
• 16 Cordero P, Campion J, Milagro FI et al. Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet. J. Physiol. Biochem. 67(3), 463–470 (2011).
  Medline CASGoogle Scholar
• 17 Abete I, Gomez-Uriz AM, Mansego ML et al. Epigenetic changes in the methylation patterns of KCNQ1 and WT1 after a weight loss intervention program in obese stroke patients. Curr. Neurovasc. Res. 12(4), 321–333 (2015).
  Medline CASGoogle Scholar
• 18 Amaral CLD, Milagro FI, Curi R, Martínez JA. DNA methylation pattern in overweight women under an energy-restricted diet supplemented with fish oil. BioMed Res. Int. 2014, 675021 (2014).
  MedlineGoogle Scholar
• 19 Campión J, Milagro FI, Goyenechea E, Martínez JA. TNF-α promoter methylation as a predictive biomarker for weight-loss response. Obesity 17(6), 1293–1297 (2009).
  Medline CASGoogle Scholar
• 20 Crujeiras AB, Campion J, Diaz-Lagares A et al. Association of weight regain with specific methylation levels in the NPY and POMC promoters in leukocytes of obese men: a translational study. Regul. Pept. 186, 1–6 (2013).
  Medline CASGoogle Scholar
• 21 Mansego ML, Milagro FI, Zulet MA, Martinez JA. SH2B1 CpG-SNP is associated with body weight reduction in obese subjects following a dietary restriction program. Ann. Nutr. Metab. 66(1), 1–9 (2014).
  MedlineGoogle Scholar
• 22 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. 58(7), 1528–1536 (2014).
  Medline CASGoogle Scholar
• 23 Milagro FI, Gómez-Abellán P, Campión J, Martínez JA, Ordovás JM, Garaulet M. CLOCK, PER2 and BMAL1 DNA methylation: association with obesity and metabolic syndrome characteristics and monounsaturated fat intake. Chronobiol. Int. 29(9), 1180–1194 (2012).
  Medline CASGoogle Scholar
• 24 Samblas M, Milagro FI, Gómez-Abellán P, Martínez JA, Garaulet M. Methylation on the Circadian Gene BMAL1 Is Associated with the Effects of a Weight Loss Intervention on Serum Lipid Levels. J. Biol. Rhythms 31(3), 308–317 (2016).
  Medline CASGoogle Scholar
• 25 De La Iglesia R, Mansego ML, Sanchez-Muniz FJ, Zulet MA, Martinez JA. Arylesterase activity is associated with antioxidant intake and paraoxonase-1 (PON1) gene methylation in metabolic syndrome patients following an energy restricted diet. EXCLI J. 13, 416–426 (2014).
  MedlineGoogle Scholar
• 26 Lopez-Legarrea P, Mansego ML, Zulet MA, Martinez JA. 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. 53(3), 139–144 (2013).
  Medline CASGoogle Scholar
• 27 Milagro FI, Campión 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. 25(4), 1378–1389 (2011).
  Medline CASGoogle Scholar
• 28 Perez-Cornago A, Mansego ML, Zulet MA, Martinez JA. DNA hypermethylation of the serotonin receptor type-2A gene is associated with a worse response to a weight loss intervention in subjects with metabolic syndrome. Nutrients 6(6), 2387–2403 (2014).
  Medline CASGoogle Scholar
• 29 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. 10(4), 671–678 (2014).
  MedlineGoogle Scholar
• 30 Marchi M, Lisi S, Curcio M et al. Human leptin tissue distribution, but not weight loss-dependent change in expression, is associated with methylation of its promoter. Epigenetics 6(10), 1198–1206 (2011).
  Medline CASGoogle Scholar
• 31 Nicoletti CF, Nonino CB, De Oliveira BaP et al. DNA methylation and hydroxymethylation levels in relation to two weight loss strategies: energy-restricted diet or bariatric surgery. Obes. Surg. 26(3), 603–611 (2016).
  MedlineGoogle Scholar
• 32 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. 91(2), 309–320 (2010).
  Medline CASGoogle Scholar
• 33 Moleres A, Campion 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. 27(6), 2504–2512 (2013).
  Medline CASGoogle Scholar
• 34 Ronn T, Volkov P, Davegardh C et al. A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet. 9(6), e1003572 (2013). • This EWAS identified three (GATA2, PIP4K2A and HDAC4) of the six genes that were reproduced across three other EWAS.
  MedlineGoogle Scholar
• 35 Barres R, Kirchner H, Rasmussen M et al. Weight Loss after Gastric Bypass Surgery in Human Obesity Remodels Promoter Methylation. Cell Rep. 3(4), 1020–1027 (2013). • This epigenome-wide association study (EWAS) identified five of the six genes that were reproduced across three other EWAS.
  Medline CASGoogle Scholar
• 36 Benton MC, Johnstone A, Eccles D et al. An analysis of DNA methylation in human adipose tissue reveals differential modification of obesity genes before and after gastric bypass and weight loss. Genome Biol. 16, 8 (2015).
  Medline CASGoogle Scholar
• 37 Dahlman I, Sinha I, Gao H et al. The fat cell epigenetic signature in post-obese women is characterized by global hypomethylation and differential DNA methylation of adipogenesis genes. Int. J. Obes. (Lond.) 39(6), 910–919 (2015). • This EWAS identified three (SDK1, RREB1 and HDAC4) of the six genes that were reproduced across three other EWAS.
  CASGoogle Scholar
• 38 Donkin I, Versteyhe S, Ingerslev LR et al. Obesity and bariatric surgery drive epigenetic variation of spermatozoa in humans. Cell Metab. 23(2), 369–378 (2016). • This EWAS identified all six genes (GATA2, TCF7L2, SDK1, PIP4K2A, RREB1 and HDAC4) that were reproduced across three other EWAS.
  Medline CASGoogle Scholar
• 39 Multhaup ML, Seldin MM, Jaffe AE et al. Mouse-human experimental epigenetic analysis unmasks dietary targets and genetic liability for diabetic phenotypes. Cell Metab. 21(1), 138–149 (2015). • This EWAS identified one of the six genes that were reproduced across three other EWAS [TCF7L2].
  Medline CASGoogle Scholar
• 40 Nilsson EK, Ernst B, Voisin S et al. Roux-en Y gastric bypass surgery induces genome-wide promoter-specific changes in DNA methylation in whole blood of obese patients. PLoS ONE 10(2), e0115186 (2015).
  MedlineGoogle Scholar
• 41 Campion J, Milagro FI, Goyenechea E, Martinez JA. TNF-alpha promoter methylation as a predictive biomarker for weight-loss response. Obesity 17(6), 1293–1297 (2009).
  Medline CASGoogle Scholar
• 42 Irizarry RA, Ladd-Acosta C, Carvalho B et al. Comprehensive high-throughput arrays for relative methylation (CHARM). Genome Res. 18(5), 780–790 (2008).
  Medline CASGoogle Scholar
• 43 Boyle P, Clement K, Gu H et al. Gel-free multiplexed reduced representation bisulfite sequencing for large-scale DNA methylation profiling. Genome Biol. 13(10), R92 (2012).
  Medline CASGoogle Scholar
• 44 Bell JT, Pai AA, Pickrell JK et al. DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. Genome Biol. 12(1), R10 (2011).
  Medline CASGoogle Scholar
• 45 Gertz J, Varley KE, Reddy TE et al. Analysis of DNA methylation in a three-generation family reveals widespread genetic influence on epigenetic regulation. PLoS Genet. 7(8), e1002228 (2011).
  Medline CASGoogle Scholar
• 46 Cooper WN, Khulan B, Owens S et al. DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: results of a pilot randomized controlled trial. FASEB J. 26(5), 1782–1790 (2012).
  Medline CASGoogle Scholar
• 47 Drake AJ, Mcpherson RC, Godfrey KM et al. An unbalanced maternal diet in pregnancy associates with offspring epigenetic changes in genes controlling glucocorticoid action and foetal growth. Clin. Endocrinol. (Oxf.) 77(6), 808–815 (2012).
  Medline CASGoogle Scholar
• 48 Heijmans BT, Tobi EW, Stein AD et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc. Natl Acad. Sci. USA 105(44), 17046–17049 (2008).
  Medline CASGoogle Scholar
• 49 Tobi EW, Goeman JJ, Monajemi R et al. DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nat. Commun. 5, 5592 (2014).
  Medline CASGoogle Scholar
• 50 Heijmans BT, Tobi EW, Stein AD et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc. Natl Acad. Sci. USA 105(44), 17046–17049 (2008).
  Medline CASGoogle Scholar
• 51 Eckhardt F, Lewin J, Cortese R et al. DNA methylation profiling of human chromosomes 6, 20 and 22. Nat. Genet. 38(12), 1378–1385 (2006).
  Medline CASGoogle Scholar
• 52 Moverare-Skrtic S, Mellstrom D, Vandenput L, Ehrich M, Ohlsson C. Peripheral blood leukocyte distribution and body mass index are associated with the methylation pattern of the androgen receptor promoter. Endocrine 35(2), 204–210 (2009).
  Medline CASGoogle Scholar
• 53 Bjornsson HT, Sigurdsson MI, Fallin MD et al. Intra-individual change over time in DNA methylation with familial clustering. JAMA 299(24), 2877–2883 (2008).
  Medline CASGoogle Scholar
• 54 Heijmans BT, Mill J. Commentary: the seven plagues of epigenetic epidemiology. Int. J. Epidemiol. 41(1), 74–78 (2012).
  MedlineGoogle Scholar
• 55 Liu Y, Aryee MJ, Padyukov L et al. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nat. Biotechnol. 31(2), 142–147 (2013).
  Medline CASGoogle Scholar
• 56 Koestler DC, Christensen B, Karagas MR et al. Blood-based profiles of DNA methylation predict the underlying distribution of cell types: a validation analysis. Epigenetics 8(8), 816–826 (2013).
  Medline CASGoogle Scholar
• 57 Demerath EW, Guan W, Grove ML et al. Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci. Hum. Mol. Genet. 24(15), 4464–4479 (2015).
  Medline CASGoogle Scholar
• 58 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. 91(2), 309–320 (2010).
  Medline CASGoogle Scholar
• 59 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. 2(49), 49ra67 (2010).
  MedlineGoogle Scholar
• 60 Birney E, Smith GD, Greally JM. Epigenome-wide association studies and the interpretation of disease -omics. PLoS Genet. 12(6), e1006105 (2016).
  MedlineGoogle Scholar
• 61 Aron-Wisnewsky J, Julia Z, Poitou C et al. Effect of bariatric surgery-induced weight loss on SR-BI-, ABCG1-, and ABCA1-mediated cellular cholesterol efflux in obese women. J. Clin. Endocrinol. Metab. 96(4), 1151–1159 (2011).
  Medline CASGoogle Scholar
• 62 Johansson LE, Danielsson AP, Parikh H et al. Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance. Am. J. Clin. Nutr. 96(1), 196–207 (2012).
  Medline CASGoogle Scholar