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Open Access 01-12-2022 | Obesity | Review

Recent progress in epigenetics of obesity

Authors: Feng-Yao Wu, Rui-Xing Yin

Published in: Diabetology & Metabolic Syndrome | Issue 1/2022

Abstract

Nowadays, obesity is one of the largest public health problems worldwide. In the last few decades, there has been a marked increase in the obesity epidemic and its related comorbidities. Worldwide, more than 2.2 billion people (33%) are affected by overweight or obesity (712 million, 10%) and its associated metabolic complications. Although a high heritability of obesity has been estimated, the genetic variants conducted from genetic association studies only partially explain the variation of body mass index. This has led to a growing interest in understanding the potential role of epigenetics as a key regulator of gene-environment interactions on the development of obesity and its associated complications. Rapid advances in epigenetic research methods and reduced costs of epigenome-wide association studies have led to a great expansion of population-based studies. The field of epigenetics and metabolic diseases such as obesity has advanced rapidly in a short period of time. The main epigenetic mechanisms include DNA methylation, histone modifications, microRNA (miRNA)-mediated regulation and so on. DNA methylation is the most investigated epigenetic mechanism. Preliminary evidence from animal and human studies supports the effect of epigenetics on obesity. Studies of epigenome-wide association studies and genome-wide histone modifications from different biological specimens such as blood samples (newborn, children, adolescent, youth, woman, man, twin, race, and meta-analysis), adipose tissues, skeletal muscle cells, placenta, and saliva have reported the differential expression status of multiple genes before and after obesity interventions and have identified multiple candidate genes and biological markers. These findings may improve the understanding of the complex etiology of obesity and its related comorbidities, and help to predict an individual’s risk of obesity at a young age and open possibilities for introducing targeted prevention and treatment strategies.

GBD 2015 Obesity Collaborators, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, et al. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017;377:13–27. https://doi.org/10.1056/NEJMoa1614362.

Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB. Years of life lost due to obesity. JAMA. 2003;289:187–93. https://doi.org/10.1001/jama.289.2.187.CrossRefPubMed

Smith KB, Smith MS. Obesity statistics. Prim Care. 2016;43(121–35):ix. https://doi.org/10.1016/j.pop.2015.10.001.CrossRef

GBD 2017 Risk Factor Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2017;392:1923–94. https://doi.org/10.1016/S0140-6736(18)32225-6.CrossRef

Pigeyre M, Yazdi FT, Kaur Y, Meyre D. Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity. Clin Sci (Lond). 2016;130:943–86. https://doi.org/10.1042/CS20160136.CrossRef

Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003;33(Suppl):245–54. https://doi.org/10.1038/ng1089.CrossRefPubMed

Regan JA, Shah SH. Obesity genomics and metabolomics: a nexus of cardiometabolic risk. Curr Cardiol Rep. 2020;22:174. https://doi.org/10.1007/s11886-020-01422-x.CrossRefPubMedPubMedCentral

Thaker VV. Genetic and epigenetic causes of obesity. Adolesc Med State Art Rev. 2017;28:379–405.PubMedPubMedCentral

Lopomo A, Burgio E, Migliore L. Epigenetics of obesity. Prog Mol Biol Transl Sci. 2016;140:151–84. https://doi.org/10.1016/bs.pmbts.2016.02.002.CrossRefPubMed

10.

Richards EJ. Inherited epigenetic variation–revisiting soft inheritance. Nat Rev Genet. 2006;7:395–401. https://doi.org/10.1038/nrg1834.CrossRefPubMed

11.

Trerotola M, Relli V, Simeone P, Alberti S. Epigenetic inheritance and the missing heritability. Hum Genomics. 2015;9:17. https://doi.org/10.1186/s40246-015-0041-3.CrossRefPubMedPubMedCentral

12.

Szyf M. Nongenetic inheritance and transgenerational epigenetics. Trends Mol Med. 2015;21:134–44. https://doi.org/10.1016/j.molmed.2014.12.004.CrossRefPubMed

13.

Junien C, Nathanielsz P. Report on the IASO Stock Conference 2006: early and lifelong environmental epigenomic programming of metabolic syndrome, obesity and type II diabetes. Obes Rev. 2007;8:487–502. https://doi.org/10.1111/j.1467-789X.2007.00371.x.CrossRefPubMed

14.

Teh AL, Pan H, Chen L, Ong ML, Dogra S, Wong J, et al. The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes. Genome Res. 2014;24:1064–74. https://doi.org/10.1101/gr.171439.113.CrossRefPubMedPubMedCentral

15.

Grundberg E, Meduri E, Sandling JK, Hedman AK, Keildson S, Buil A, et al. Global analysis of DNAm variation in adipose tissue from twins reveals links to disease-associated variants in distal regulatory elements. Am J Hum Genet. 2013;93:876–90. https://doi.org/10.1016/j.ajhg.2013.10.004.CrossRefPubMedPubMedCentral

16.

Rönn T, Volkov P, Gillberg L, Kokosar M, Perfilyev A, Jacobsen AL, et al. Impact of age, BMI and HbA1c levels on the genome-wide DNAm and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood. Hum Mol Genet. 2015;24:3792–813. https://doi.org/10.1093/hmg/ddv124.CrossRefPubMed

17.

van Dijk SJ, Molloy PL, Varinli H, Morrison JL, Muhlhausler BS. Members of EpiSCOPE. Epigenetics and human obesity. Int J Obes (Lond). 2015;39:85–97. https://doi.org/10.1038/ijo.2014.34.CrossRef

18.

van Dijk SJ, Tellam RL, Morrison JL, Muhlhausler BS, Molloy PL. Recent developments on the role of epigenetics in obesity and metabolic disease. Clin Epigenetics. 2015;7:66. https://doi.org/10.1186/s13148-015-0101-5.CrossRefPubMedPubMedCentral

19.

Ling C, Rönn T. Epigenetics in human obesity and type 2 diabetes. Cell Metab. 2019;29:1028–44. https://doi.org/10.1016/j.cmet.2019.03.009.CrossRefPubMedPubMedCentral

20.

Martin CL, Jima D, Sharp GC, McCullough LE, Park SS, Gowdy KM, et al. Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study. Epigenetics. 2019;14:325–40. https://doi.org/10.1080/15592294.2019.1581594.CrossRefPubMedPubMedCentral

21.

Jönsson J, Renault KM, García-Calzón S, Perfilyev A, Estampador AC, Nørgaard K, et al. Lifestyle intervention in pregnant women with obesity impacts cord blood DNA methylation, which associates with body composition in the offspring. Diabetes. 2021;70:854–66. https://doi.org/10.2337/db20-0487.CrossRefPubMedPubMedCentral

22.

Huang RC, Garratt ES, Pan H, Wu Y, Davis EA, Barton SJ, et al. Genome-wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood. Epigenetics. 2015;10:995–1005. https://doi.org/10.1080/15592294.2015.1080411.CrossRefPubMedPubMedCentral

23.

Fradin D, Boëlle PY, Belot MP, Lachaux F, Tost J, Besse C, et al. Genome-wide methylation analysis identifies specific epigenetic marks in severely obese children. Sci Rep. 2017;7:46311. https://doi.org/10.1038/srep46311.CrossRefPubMedPubMedCentral

24.

Rzehak P, Covic M, Saffery R, Reischl E, Wahl S, Grote V, et al. DNA-methylation and body composition in preschool children: Epigenome-wide-analysis in the European Childhood Obesity Project (CHOP)-Study. Sci Rep. 2017;7:14349. https://doi.org/10.1038/s41598-017-13099-4.CrossRefPubMedPubMedCentral

25.

Li Y, Zhou Y, Zhu L, Liu G, Wang X, Wang X, et al. Genome-wide analysis reveals that altered methylation in specific CpG loci is associated with childhood obesity. J Cell Biochem. 2018;119:7490–7. https://doi.org/10.1002/jcb.27059.CrossRefPubMed

26.

Samblas M, Milagro FI, Mansego ML, Marti A, Martinez JA, GENOI members. PTPRS and PER3 methylation levels are associated with childhood obesity: results from a genome-wide methylation analysis. Pediatr Obes. 2018;13:149–58. https://doi.org/10.1111/ijpo.12224.CrossRefPubMed

27.

Huang JV, Cardenas A, Colicino E, Schooling CM, Rifas-Shiman SL, Agha G, et al. DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescence. Epigenetics. 2018;13:1072–87. https://doi.org/10.1080/15592294.2018.1543503.CrossRefPubMedPubMedCentral

28.

He F, Berg A, Imamura Kawasawa Y, Bixler EO, Fernandez-Mendoza J, Whitsel EA, et al. Association between DNA methylation in obesity-related genes and body mass index percentile in adolescents. Sci Rep. 2019;9:2079. https://doi.org/10.1038/s41598-019-38587-7.CrossRefPubMedPubMedCentral

29.

Sherwood WB, Bion V, Lockett GA, Ziyab AH, Soto-Ramírez N, Mukherjee N, et al. Duration of breastfeeding is associated with leptin (LEP) DNA methylation profiles and BMI in 10-year-old children. Clin Epigenetics. 2019;11:128. https://doi.org/10.1186/s13148-019-0727-9.CrossRefPubMedPubMedCentral

30.

Wang J, Zhang H, Rezwan FI, Relton C, Arshad SH, Holloway JW. Pre-adolescence DNA methylation is associated with BMI status change from pre- to post-adolescence. Clin Epigenetics. 2021;13:64. https://doi.org/10.1186/s13148-021-01042-4.CrossRefPubMedPubMedCentral

31.

Vehmeijer FOL, Küpers LK, Sharp GC, Salas LA, Lent S, Jima DD, et al. DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies. Genome Med. 2020;12:105. https://doi.org/10.1186/s13073-020-00810-w.CrossRefPubMedPubMedCentral

32.

Xu X, Su S, Barnes VA, De Miguel C, Pollock J, Ownby D, et al. A genome-wide methylation study on obesity: differential variability and differential methylation. Epigenetics. 2013;8:522–33. https://doi.org/10.4161/epi.24506.CrossRefPubMedPubMedCentral

33.

Wang X, Pan Y, Zhu H, Hao G, Huang Y, Barnes V, et al. An epigenome-wide study of obesity in African American youth and young adults: novel findings, replication in neutrophils, and relationship with gene expression. Clin Epigenetics. 2018;10:3. https://doi.org/10.1186/s13148-017-0435-2.CrossRefPubMedPubMedCentral

34.

Wilson LE, Harlid S, Xu Z, Sandler DP, Taylor JA. An epigenome-wide study of body mass index and DNA methylation in blood using participants from the Sister Study cohort. Int J Obes (Lond). 2017;41:194–9. https://doi.org/10.1038/ijo.2016.184.CrossRef

35.

Kvaløy K, Page CM, Holmen TL. Epigenome-wide methylation differences in a group of lean and obese women—a HUNT Study. Sci Rep. 2018;8:16330. https://doi.org/10.1038/s41598-018-34003-8.CrossRefPubMedPubMedCentral

36.

Shen J, Song R, Ye Y, Wu X, Chow WH, Zhao H. HIF3A DNA methylation, obesity and weight gain, and breast cancer risk among Mexican American women. Obes Res Clin Pract. 2020;14:548–53. https://doi.org/10.1016/j.orcp.2020.10.001.CrossRefPubMed

37.

Guay SP, Brisson D, Lamarche B, Biron S, Lescelleur O, Biertho L, et al. ADRB3 gene promoter DNA methylation in blood and visceral adipose tissue is associated with metabolic disturbances in men. Epigenomics. 2014;6:33–43. https://doi.org/10.2217/epi.13.82.CrossRefPubMed

38.

Skuladottir GV, Nilsson EK, Mwinyi J, Schiöth HB. One-night sleep deprivation induces changes in the DNA methylation and serum activity indices of stearoyl-CoA desaturase in young healthy men. Lipids Health Dis. 2016;15:137. https://doi.org/10.1186/s12944-016-0309-1.CrossRefPubMedPubMedCentral

39.

Keller M, Yaskolka Meir A, Bernhart SH, Gepner Y, Shelef I, Schwarzfuchs D, et al. DNA methylation signature in blood mirrors successful weight-loss during lifestyle interventions: the CENTRAL trial. Genome Med. 2020;12:97. https://doi.org/10.1186/s13073-020-00794-7.CrossRefPubMedPubMedCentral

40.

Ollikainen M, Ismail K, Gervin K, Kyllönen A, Hakkarainen A, Lundbom J, et al. Genome-wide blood DNA methylation alterations at regulatory elements and heterochromatic regions in monozygotic twins discordant for obesity and liver fat. Clin Epigenetics. 2015;7:39. https://doi.org/10.1186/s13148-015-0073-5.CrossRefPubMedPubMedCentral

41.

Li CX, Gao Y, Gao WJ, Yu CQ, Lyu J, Lyu RR, et al. Association between obesity and DNA methylation among the 7–16 year-old twins. Zhonghua Liu Xing Bing Xue Za Zhi. 2018;39:443–8. https://doi.org/10.3760/cma.j.issn.0254-6450.2018.04.011.CrossRefPubMed

42.

Li W, Zhang D, Wang W, Wu Y, Mohammadnejad A, Lund J, et al. DNA methylome profiling in identical twin pairs discordant for body mass index. Int J Obes (Lond). 2019;43:2491–9. https://doi.org/10.1038/s41366-019-0382-4.CrossRef

43.

Demerath EW, Guan W, Grove ML, Aslibekyan S, Mendelson M, Zhou YH, 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. 2015;24:4464–79. https://doi.org/10.1093/hmg/ddv161.CrossRefPubMedPubMedCentral

44.

Xu K, Zhang X, Wang Z, Hu Y, Sinha R. Epigenome-wide association analysis revealed that SOCS3 methylation influences the effect of cumulative stress on obesity. Biol Psychol. 2018;131:63–71. https://doi.org/10.1016/j.biopsycho.2016.11.001.CrossRefPubMed

45.

Sun D, Zhang T, Su S, Hao G, Chen T, Li QZ, et al. Body mass index drives changes in DNA methylation: a longitudinal study. Circ Res. 2019;125:824–33. https://doi.org/10.1161/CIRCRESAHA.119.315397.CrossRefPubMedPubMedCentral

46.

Meeks KAC, Henneman P, Venema A, Burr T, Galbete C, Danquah I, et al. An epigenome-wide association study in whole blood of measures of adiposity among Ghanaians: the RODAM study. Clin Epigenetics. 2017;9:103. https://doi.org/10.1186/s13148-017-0403-x.CrossRefPubMedPubMedCentral

47.

Giri AK, Prasad G, Bandesh K, Parekatt V, Mahajan A, Banerjee P, et al. Multifaceted genome-wide study identifies novel regulatory loci in SLC22A11 and ZNF45 for body mass index in Indians. Mol Genet Genomics. 2020;295:1013–26. https://doi.org/10.1007/s00438-020-01678-6.CrossRefPubMed

48.

Dick KJ, Nelson CP, Tsaprouni L, Sandling JK, Aïssi D, Wahl S, et al. DNA methylation and body-mass index: a genome-wide analysis. Lancet. 2014;383:1990–8. https://doi.org/10.1016/S0140-6736(13)62674-4.CrossRefPubMed

49.

Sayols-Baixeras S, Subirana I, Fernández-Sanlés A, Sentí M, Lluís-Ganella C, Marrugat J, et al. DNA methylation and obesity traits: an epigenome-wide association study. The REGICOR study. Epigenetics. 2017;12:909–16. https://doi.org/10.1080/15592294.2017.1363951.CrossRefPubMedPubMedCentral

50.

Mendelson MM, Marioni RE, Joehanes R, Liu C, Hedman ÅK, Aslibekyan S, et al. Association of body mass index with DNA methylation and gene expression in blood cells and relations to cardiometabolic disease: a Mendelian randomization approach. PLoS Med. 2017;14: e1002215. https://doi.org/10.1371/journal.pmed.1002215.CrossRefPubMedPubMedCentral

51.

Dhana K, Braun KVE, Nano J, Voortman T, Demerath EW, Guan W, et al. An epigenome-wide association study of obesity-related traits. Am J Epidemiol. 2018;187:1662–9. https://doi.org/10.1093/aje/kwy025.CrossRefPubMedPubMedCentral

52.

Do WL, Gohar J, McCullough LE, Galaviz KI, Conneely KN, Narayan KMV. Examining the association between adiposity and DNA methylation: a systematic review and meta-analysis. Obes Rev. 2021;22: e13319. https://doi.org/10.1111/obr.13319.CrossRefPubMed

53.

Nikpay M, Ravati S, Dent R, McPherson R. Epigenome-wide study identified methylation sites associated with the risk of obesity. Nutrients. 2021;13:1984. https://doi.org/10.3390/nu13061984.CrossRefPubMedPubMedCentral

54.

Benton MC, Johnstone A, Eccles D, Harmon B, Hayes MT, Lea RA, 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. 2015;16:8. https://doi.org/10.1186/s13059-014-0569-x.CrossRefPubMedPubMedCentral

55.

Dahlman I, Sinha I, Gao H, Brodin D, Thorell A, Rydén M, 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). 2015;39:910–9. https://doi.org/10.1038/ijo.2015.31.CrossRef

56.

Rönn T, Volkov P, Davegårdh C, Dayeh T, Hall E, Olsson AH, et al. A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet. 2013;9: e1003572. https://doi.org/10.1371/journal.pgen.1003572.CrossRefPubMedPubMedCentral

57.

Macartney-Coxson D, Benton MC, Blick R, Stubbs RS, Hagan RD, Langston MA. Genome-wide DNA methylation analysis reveals loci that distinguish different types of adipose tissue in obese individuals. Clin Epigenetics. 2017;9:48. https://doi.org/10.1186/s13148-017-0344-4.CrossRefPubMedPubMedCentral

58.

Keller M, Hopp L, Liu X, Wohland T, Rohde K, Cancello R, et al. Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity. Mol Metab. 2016;6:86–100. https://doi.org/10.1016/j.molmet.2016.11.003.CrossRefPubMedPubMedCentral

59.

Crujeiras AB, Diaz-Lagares A, Sandoval J, Milagro FI, Navas-Carretero S, Carreira MC, et al. DNA methylation map in circulating leukocytes mirrors subcutaneous adipose tissue methylation pattern: a genome-wide analysis from non-obese and obese patients. Sci Rep. 2017;7:41903. https://doi.org/10.1038/srep41903.CrossRefPubMedPubMedCentral

60.

Turner DC, Gorski PP, Maasar MF, Seaborne RA, Baumert P, Brown AD, et al. DNA methylation across the genome in aged human skeletal muscle tissue and muscle-derived cells: the role of HOX genes and physical activity. Sci Rep. 2020;10:15360. https://doi.org/10.1038/s41598-020-72730-z.CrossRefPubMedPubMedCentral

61.

Prats-Puig A, García-Retortillo S, Puig-Parnau M, Vasileva F, Font-Lladó R, Xargay-Torrent S, et al. DNA methylation reorganization of skeletal muscle-specific genes in response to gestational obesity. Front Physiol. 2020;11:938. https://doi.org/10.3389/fphys.2020.00938.CrossRefPubMedPubMedCentral

62.

Sillanpää E, Heikkinen A, Kankaanpää A, Paavilainen A, Kujala UM, Tammelin TH, et al. Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning. Clin Epigenetics. 2021;13:110. https://doi.org/10.1186/s13148-021-01094-6.CrossRefPubMedPubMedCentral

63.

Day SE, Garcia LA, Coletta RL, Campbell LE, Benjamin TR, De Filippis EA, et al. Alterations of sorbin and SH3 domain containing 3 (SORBS3) in human skeletal muscle following Roux-en-Y gastric bypass surgery. Clin Epigenetics. 2017;9:96. https://doi.org/10.1186/s13148-017-0396-5.CrossRefPubMedPubMedCentral

64.

Nogues P, Dos Santos E, Jammes H, Berveiller P, Arnould L, Vialard F, et al. Maternal obesity influences expression and DNA methylation of the adiponectin and leptin systems in human third-trimester placenta. Clin Epigenetics. 2019;11:20. https://doi.org/10.1186/s13148-019-0612-6.CrossRefPubMedPubMedCentral

65.

Gagné-Ouellet V, Breton E, Thibeault K, Fortin CA, Desgagné V, Girard Tremblay É, et al. Placental epigenome-wide association study identified loci associated with childhood adiposity at 3 years of age. Int J Mol Sci. 2020;21:7201. https://doi.org/10.3390/ijms21197201.CrossRefPubMedCentral

66.

Daniels TE, Sadovnikoff AI, Ridout KK, Lesseur C, Marsit CJ, Tyrka AR. Associations of maternal diet and placenta leptin methylation. Mol Cell Endocrinol. 2020;505: 110739. https://doi.org/10.1016/j.mce.2020.110739.CrossRefPubMedPubMedCentral

67.

Breton E, Gagné-Ouellet V, Thibeault K, Guérin R, Van Lieshout R, Perron P, et al. Placental NEGR1 DNA methylation is associated with BMI and neurodevelopment in preschool-age children. Epigenetics. 2020;15:323–35. https://doi.org/10.1080/15592294.2019.1666653.CrossRefPubMed

68.

Shrestha D, Ouidir M, Workalemahu T, Zeng X, Tekola-Ayele F. Placental DNA methylation changes associated with maternal prepregnancy BMI and gestational weight gain. Int J Obes (Lond). 2020;44:1406–16. https://doi.org/10.1038/s41366-020-0546-2.CrossRef

69.

Rounge TB, Page CM, Lepistö M, Ellonen P, Andreassen BK, Weiderpass E. Genome-wide DNA methylation in saliva and body size of adolescent girls. Epigenomics. 2016;8:1495–505. https://doi.org/10.2217/epi-2016-0045.CrossRefPubMed

70.

Oelsner KT, Guo Y, To SB, Non AL, Barkin SL. Maternal BMI as a predictor of methylation of obesity-related genes in saliva samples from preschool-age Hispanic children at-risk for obesity. BMC Genomics. 2017;18:57. https://doi.org/10.1186/s12864-016-3473-9.CrossRefPubMedPubMedCentral

71.

Dunstan J, Bressler JP, Moran TH, Pollak JS, Hirsch AG, Bailey-Davis L, et al. Associations of LEP, CRH, ICAM-1, and LINE-1 methylation, measured in saliva, with waist circumference, body mass index, and percent body fat in mid-childhood. Clin Epigenetics. 2017;9:29. https://doi.org/10.1186/s13148-017-0327-5.CrossRefPubMedPubMedCentral

72.

Kaufman J, Montalvo-Ortiz JL, Holbrook H, O’Loughlin K, Orr C, Kearney C, et al. Adverse childhood experiences, epigenetic measures, and obesity in youth. J Pediatr. 2018;202:150-6.e3. https://doi.org/10.1016/j.jpeds.2018.06.051.CrossRefPubMedPubMedCentral

73.

Li C, Wang Z, Hardy T, Huang Y, Hui Q, Crusto CA, et al. Association of obesity with DNA methylation age acceleration in African American mothers from the InterGEN Study. Int J Mol Sci. 2019;20:4273. https://doi.org/10.3390/ijms20174273.CrossRefPubMedCentral

74.

Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21:381–95. https://doi.org/10.1038/cr.2011.22.CrossRefPubMedPubMedCentral

75.

Keating ST, El-Osta A. Epigenetics and metabolism. Circ Res. 2015;116:715–36. https://doi.org/10.1161/CIRCRESAHA.116.303936.CrossRefPubMed

76.

Zhang T, Cooper S, Brockdorff N. The interplay of histone modifications—writers that read. EMBO Rep. 2015;16:1467–81. https://doi.org/10.15252/embr.201540945.CrossRefPubMedPubMedCentral

77.

Zhang Q, Ramlee MK, Brunmeir R, Villanueva CJ, Halperin D, Xu F. Dynamic and distinct histone modifications modulate the expression of key adipogenesis regulatory genes. Cell Cycle. 2012;11:4310–22. https://doi.org/10.4161/cc.22224.CrossRefPubMedPubMedCentral

78.

Leung A, Parks BW, Du J, Trac C, Setten R, Chen Y, et al. Open chromatin profiling in mice livers reveals unique chromatin variations induced by high fat diet. J Biol Chem. 2014;289:23557–67. https://doi.org/10.1074/jbc.M114.581439.CrossRefPubMedPubMedCentral

79.

Leung A, Trac C, Du J, Natarajan R, Schones DE. Persistent chromatin modifications induced by high fat diet. J Biol Chem. 2016;291:10446–55. https://doi.org/10.1074/jbc.M115.711028.CrossRefPubMedPubMedCentral

80.

Funato H, Tsai AL, Willie JT, Kisanuki Y, Williams SC, Sakurai T, et al. Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves leptin sensitivity. Cell Metab. 2009;9:64–76. https://doi.org/10.1016/j.cmet.2008.10.010.CrossRefPubMedPubMedCentral

81.

Hauck AK, Zhou T, Upadhyay A, Sun Y, O’Connor MB, Chen Y, et al. Histone carbonylation is a redox-regulated epigenomic mark that accumulates with obesity and aging. Antioxidants (Basel). 2020;9:1210. https://doi.org/10.3390/antiox9121210.CrossRef

82.

Masi S, Ambrosini S, Mohammed SA, Sciarretta S, Lüscher TF, Paneni F, et al. Epigenetic remodeling in obesity-related vascular disease. Antioxid Redox Signal. 2021;34:1165–99. https://doi.org/10.1089/ars.2020.8040.CrossRefPubMed

83.

Wang Z, Zhu M, Wang M, Gao Y, Zhang C, Liu S, et al. Integrated multiomic analysis reveals the high-fat diet induced activation of the mapk signaling and inflammation associated metabolic cascades via histone modification in adipose tissues. Front Genet. 2021;12: 650863. https://doi.org/10.3389/fgene.2021.650863.CrossRefPubMedPubMedCentral

84.

Lunke S, Maxwell S, Khurana I, Harikrishnan KN, Okabe J, Al-Hasani K, et al. Epigenetic evidence of an Ac/Dc axis by VPA and SAHA. Clin Epigenetics. 2021;13:58. https://doi.org/10.1186/s13148-021-01050-4.CrossRefPubMedPubMedCentral

85.

Małodobra-Mazur M, Cierzniak A, Myszczyszyn A, Kaliszewski K, Dobosz T. Histone modifications influence the insulin-signaling genes and are related to insulin resistance in human adipocytes. Int J Biochem Cell Biol. 2021;137: 106031. https://doi.org/10.1016/j.biocel.2021.106031.CrossRefPubMed

86.

Pan MH, Zhu CC, Ju JQ, Xu Y, Luo SM, Sun SC, et al. Single-cell transcriptome analysis reveals that maternal obesity affects DNA repair, histone methylation, and autophagy level in mouse embryos. J Cell Physiol. 2021;236:4944–53. https://doi.org/10.1002/jcp.30201.CrossRefPubMed

87.

La Sala L, Crestani M, Garavelli S, de Candia P, Pontiroli AE. Does microRNA perturbation control the mechanisms linking obesity and diabetes? Implications for cardiovascular risk. Int J Mol Sci. 2020;22:143. https://doi.org/10.3390/ijms22010143.CrossRefPubMedCentral

88.

Pasquinelli AE. MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet. 2012;13:271–82. https://doi.org/10.1038/nrg3162.CrossRefPubMed

89.

Sluijter JP, Pasterkamp G. MicroRNAs: the swing voters in vascular disease waiting for a program. Circ Res. 2017;120:5–7. https://doi.org/10.1161/CIRCRESAHA.116.310215.CrossRefPubMed

90.

Vishnoi A, Rani S. MiRNA biogenesis and regulation of diseases: an overview. Methods Mol Biol. 2017;1509:1–10. https://doi.org/10.1007/978-1-4939-6524-3_1.CrossRefPubMed

91.

Silveira A, Gomes J, Roque F, Fernandes T, de Oliveira EM. MicroRNAs in obesity-associated disorders: the role of exercise training. Obes Facts. 2022;15:105–17. https://doi.org/10.1159/000517849.CrossRefPubMedPubMedCentral

92.

Gharanei S, Shabir K, Brown JE, Weickert MO, Barber TM, Kyrou I, et al. Regulatory microRNAs in brown, brite and white adipose tissue. Cells. 2020;9:2489. https://doi.org/10.3390/cells9112489.CrossRefPubMedCentral

93.

Kozomara A, Birgaoanu M, Griffiths-Jones S. miRBase: from microRNA sequences to function. Nucleic Acids Res. 2019;47(D1):D155–62. https://doi.org/10.1093/nar/gky1141.CrossRefPubMed

94.

Akhtar MM, Micolucci L, Islam MS, Olivieri F, Procopio AD. Bioinformatic tools for microRNA dissection. Nucleic Acids Res. 2016;44:24–44. https://doi.org/10.1093/nar/gkv1221.CrossRefPubMed

95.

Ghorai A, Ghosh U. miRNA gene counts in chromosomes vary widely in a species and biogenesis of miRNA largely depends on transcription or post-transcriptional processing of coding genes. Front Genet. 2014;5:100. https://doi.org/10.3389/fgene.2014.00100.CrossRefPubMedPubMedCentral

96.

Cruz KJC, de Oliveira ARS, Morais JBS, Severo JS, Marreiro PhD DDN. The role of micrornas on adipogenesis, chronic low grade inflammation and insulin resistance in obesity. Nutrition. 2017;35:28–35. https://doi.org/10.1016/j.nut.2016.10.003.CrossRefPubMed

97.

Heyn GS, Corrêa LH, Magalhães KG. The Impact of adipose tissue-derived mirnas in metabolic syndrome, obesity, and cancer. Front Endocrinol (Lausanne). 2020;11: 563816. https://doi.org/10.3389/fendo.2020.563816.CrossRef

98.

Gasmi A, Noor S, Menzel A, Doşa A, Pivina L, Bjørklund G. Obesity and insulin resistance: associations with chronic inflammation, genetic and epigenetic factors. Curr Med Chem. 2021;28:800–26. https://doi.org/10.2174/0929867327666200824112056.CrossRefPubMed

99.

Prats-Puig A, Ortega FJ, Mercader JM, Moreno-Navarrete JM, Moreno M, Bonet N, et al. Changes in circulating microRNAs are associated with childhood obesity. J Clin Endocrinol Metab. 2013;98:E1655–60. https://doi.org/10.1210/jc.2013-1496.CrossRefPubMed

100.

Lin H, Tas E, Børsheim E, Mercer KE. Circulating miRNA signatures associated with insulin resistance in adolescents with obesity. Diabetes Metab Syndr Obes. 2020;13:4929–39. https://doi.org/10.2147/DMSO.S273908.CrossRefPubMedPubMedCentral

101.

Iacomino G, Russo P, Marena P, Lauria F, Venezia A, Ahrens W, et al. Circulating microRNAs are associated with early childhood obesity: results of the I. Family Study. Genes Nutr. 2019;14:2. https://doi.org/10.1186/s12263-018-0622-6.CrossRefPubMedPubMedCentral

102.

Al-Rawaf HA. Circulating microRNAs and adipokines as markers of metabolic syndrome in adolescents with obesity. Clin Nutr. 2019;38:2231–8. https://doi.org/10.1016/j.clnu.2018.09.024.CrossRefPubMed

103.

Méndez-Mancilla A, Lima-Rogel V, Toro-Ortíz JC, Escalante-Padrón F, Monsiváis-Urenda AE, Noyola DE, et al. Differential expression profiles of circulating microRNAs in newborns associated to maternal pregestational overweight and obesity. Pediatr Obes. 2018;13:168–74. https://doi.org/10.1111/ijpo.12247.CrossRefPubMed

104.

Lischka J, Schanzer A, Hojreh A, Ba-Ssalamah A, de Gier C, Valent I, et al. Circulating microRNAs 34a, 122, and 192 are linked to obesity-associated inflammation and metabolic disease in pediatric patients. Int J Obes (Lond). 2021;45:1763–72. https://doi.org/10.1038/s41366-021-00842-1.CrossRef

105.

Zhao H, Shen J, Daniel-MacDougall C, Wu X, Chow WH. Plasma MicroRNA signature predicting weight gain among Mexican–American women. Obesity (Silver Spring). 2017;25:958–64. https://doi.org/10.1002/oby.21824.CrossRef

106.

Hubal MJ, Nadler EP, Ferrante SC, Barberio MD, Suh JH, Wang J, et al. Circulating adipocyte-derived exosomal MicroRNAs associated with decreased insulin resistance after gastric bypass. Obesity (Silver Spring). 2017;25:102–10. https://doi.org/10.1002/oby.21709.CrossRef

107.

Shi C, Huang F, Gu X, Zhang M, Wen J, Wang X, et al. Adipogenic miRNA and meta-signature miRNAs involved in human adipocyte differentiation and obesity. Oncotarget. 2016;7:40830–45. https://doi.org/10.18632/oncotarget.8518.CrossRefPubMedPubMedCentral

108.

Catanzaro G, Filardi T, Sabato C, Vacca A, Migliaccio S, Morano S, et al. Tissue and circulating microRNAs as biomarkers of response to obesity treatment strategies. J Endocrinol Invest. 2021;44:1159–74. https://doi.org/10.1007/s40618-020-01453-9.CrossRefPubMed

109.

Włodarski A, Strycharz J, Wróblewski A, Kasznicki J, Drzewoski J, Śliwińska A. The Role of microRNAs in metabolic syndrome-related oxidative stress. Int J Mol Sci. 2020;21:6902. https://doi.org/10.3390/ijms21186902.CrossRefPubMedCentral

110.

Ait-Aissa K, Nguyen QM, Gabani M, Kassan A, Kumar S, Choi SK, et al. MicroRNAs and obesity-induced endothelial dysfunction: key paradigms in molecular therapy. Cardiovasc Diabetol. 2020;19:136. https://doi.org/10.1186/s12933-020-01107-3.CrossRefPubMedPubMedCentral

111.

Breier BH, Vickers MH, Ikenasio BA, Chan KY, Wong WP. Fetal programming of appetite and obesity. Mol Cell Endocrinol. 2001;185:73–9. https://doi.org/10.1016/s0303-7207(01)00634-7.CrossRefPubMed

112.

Vickers MH. Developmental programming and transgenerational transmission of obesity. Ann Nutr Metab. 2014;64(Suppl 1):26–34. https://doi.org/10.1159/000360506.CrossRefPubMed

113.

Tanvig M. Offspring body size and metabolic profile—effects of lifestyle intervention in obese pregnant women. Dan Med J. 2014;61:B4893.PubMed

114.

Vickers MH, Reddy S, Ikenasio BA, Breier BH. Dysregulation of the adipoinsular axis—a mechanism for the pathogenesis of hyperleptinemia and adipogenic diabete Vickers s induced by fetal programming. J Endocrinol. 2001;170:323–32. https://doi.org/10.1677/joe.0.1700323.CrossRefPubMed

115.

Vickers MH, Ikenasio BA, Breier BH. IGF-I treatment reduces hyperphagia, obesity, and hypertension in metabolic disorders induced by fetal programming. Endocrinology. 2001;142:3964–73. https://doi.org/10.1210/endo.142.9.8390.CrossRefPubMed

116.

Vickers MH, Breier BH, McCarthy D, Gluckman PD. Sedentary behavior during postnatal life is determined by the prenatal environment and exacerbated by postnatal hypercaloric nutrition. Am J Physiol Regul Integr Comp Physiol. 2003;285:R271–3. https://doi.org/10.1152/ajpregu.00051.2003.CrossRefPubMed

117.

Stein AD, Lumey LH. The relationship between maternal and offspring birth weights after maternal prenatal famine exposure: the Dutch Famine Birth Cohort Study. Hum Biol. 2000;72:641–54.PubMed

118.

Veenendaal MV, Painter RC, de Rooij SR, Bossuyt PM, van der Post JA, Gluckman PD, et al. Transgenerational effects of prenatal exposure to the 1944–45 Dutch famine. BJOG. 2013;120:548–53. https://doi.org/10.1111/1471-0528.12136.CrossRefPubMed

119.

Ross MG, Desai M. Developmental programming of offspring obesity, adipogenesis, and appetite. Clin Obstet Gynecol. 2013;56:529–36. https://doi.org/10.1097/GRF.0b013e318299c39d.CrossRefPubMedPubMedCentral

120.

Martínez JA, Cordero P, Campión J, Milagro FI. Interplay of early-life nutritional programming on obesity, inflammation and epigenetic outcomes. Proc Nutr Soc. 2012;71:276–83. https://doi.org/10.1017/S0029665112000055.CrossRefPubMed

121.

Moreno-Mendez E, Quintero-Fabian S, Fernandez-Mejia C, Lazo-de-la-Vega-Monroy ML. Early-life programming of adipose tissue. Nutr Res Rev. 2020;33:244–59. https://doi.org/10.1017/S0954422420000037.CrossRefPubMed

122.

Painter RC, Osmond C, Gluckman P, Hanson M, Phillips DI, Roseboom TJ. Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life. BJOG. 2008;115:1243–9. https://doi.org/10.1111/j.1471-0528.2008.01822.x.CrossRefPubMed

123.

Stanner SA, Bulmer K, Andrès C, Lantseva OE, Borodina V, Poteen VV, et al. Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study. BMJ. 1997;315:1342–8. https://doi.org/10.1136/bmj.315.7119.1342.CrossRefPubMedPubMedCentral

124.

Sparén P, Vågerö D, Shestov DB, Plavinskaja S, Parfenova N, Hoptiar V, et al. Long term mortality after severe starvation during the siege of Leningrad: prospective cohort study. BMJ. 2004;328:11. https://doi.org/10.1136/bmj.37942.603970.9A.CrossRefPubMedPubMedCentral

125.

Vickers MH, Breier BH, Cutfield WS, Hofman PL, Gluckman PD. Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Am J Physiol Endocrinol Metab. 2000;279:E83–7. https://doi.org/10.1152/ajpendo.2000.279.1.E83.CrossRefPubMed

126.

Desai M, Jellyman JK, Ross MG. Epigenomics, gestational programming and risk of metabolic syndrome. Int J Obes (Lond). 2015;39:633–41. https://doi.org/10.1038/ijo.2015.13.CrossRef

127.

González-Casanova JE, Pertuz-Cruz SL, Caicedo-Ortega NH, Rojas-Gomez DM. Adipogenesis regulation and endocrine disruptors: emerging insights in obesity. Biomed Res Int. 2020;2020:7453786. https://doi.org/10.1155/2020/7453786.CrossRefPubMedPubMedCentral

128.

Kim JT, Lee HK. Childhood obesity and endocrine disrupting chemicals. Ann Pediatr Endocrinol Metab. 2017;22:219–25. https://doi.org/10.6065/apem.2017.22.4.219.CrossRefPubMedPubMedCentral

129.

Darbre PD. Endocrine disruptors and obesity. Curr Obes Rep. 2017;6:18–27. https://doi.org/10.1007/s13679-017-0240-4.CrossRefPubMedPubMedCentral

130.

Braun JM. Early-life exposure to EDCs: role in childhood obesity and neurodevelopment. Nat Rev Endocrinol. 2017;13:161–73. https://doi.org/10.1038/nrendo.2016.186.CrossRefPubMed

131.

Paciência I, Cavaleiro Rufo J, Silva D, Martins C, Mendes F, Farraia M, et al. Exposure to indoor endocrine-disrupting chemicals and childhood asthma and obesity. Allergy. 2019;74:1277–91. https://doi.org/10.1111/all.13740.CrossRefPubMed

132.

Heras-González L, Latorre JA, Martinez-Bebia M, Espino D, Olea-Serrano F, Mariscal-Arcas M. The relationship of obesity with lifestyle and dietary exposure to endocrine-disrupting chemicals. Food Chem Toxicol. 2020;136: 110983. https://doi.org/10.1016/j.fct.2019.110983.CrossRefPubMed

133.

Petrakis D, Vassilopoulou L, Mamoulakis C, Psycharakis C, Anifantaki A, Sifakis S, et al. Endocrine disruptors leading to obesity and related diseases. Int J Environ Res Public Health. 2017;14:1282. https://doi.org/10.3390/ijerph14101282.CrossRefPubMedCentral

134.

Yan Z, Zhang H, Maher C, Arteaga-Solis E, Champagne FA, Wu L, et al. Prenatal polycyclic aromatic hydrocarbon, adiposity, peroxisome proliferator-activated receptor (PPAR) γ methylation in offspring, grand-offspring mice. PLoS ONE. 2014;9: e110706. https://doi.org/10.1371/journal.pone.0110706.CrossRefPubMedPubMedCentral

135.

Anderson OS, Kim JH, Peterson KE, Sanchez BN, Sant KE, Sartor MA, et al. Novel epigenetic biomarkers mediating bisphenol A exposure and metabolic phenotypes in female mice. Endocrinology. 2017;158:31–40. https://doi.org/10.1210/en.2016-1441.CrossRefPubMed

136.

Smith CJ, Perfetti TA, Hayes AW, Berry SC. Clinical epidemiology studies on potential effects of endocrine disrupting chemicals (EDCs) should exclude subjects with obesity as determined by BMI. Regul Toxicol Pharmacol. 2020;115: 104711. https://doi.org/10.1016/j.yrtph.2020.104711.CrossRefPubMed

137.

Lin JY, Yin RX. Exposure to endocrine-disrupting chemicals and type 2 diabetes mellitus in later life. Expo Health. 2022. https://doi.org/10.1007/s12403-022-00486-0.CrossRef

Title: Recent progress in epigenetics of obesity
Authors: Feng-Yao Wu
Rui-Xing Yin
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Obesity
Obesity
Epigenetics
Published in: Diabetology & Metabolic Syndrome / Issue 1/2022
Electronic ISSN: 1758-5996
DOI: https://doi.org/10.1186/s13098-022-00947-1

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