{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:47:47Z","timestamp":1792691267287,"version":"4.5.0"},"reference-count":137,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Maternal obesity is a rapidly evolving universal epidemic leading to acute and long-term medical and obstetric health issues, including increased maternal risks of gestational diabetes, hypertension and pre-eclampsia, and the future risks for offspring\u2019s predisposition to metabolic diseases. Epigenetic modification, in particular DNA methylation, represents a mechanism whereby environmental effects impact on the phenotypic expression of human disease. Maternal obesity or overnutrition contributes to the alterations in DNA methylation during early life which, through fetal programming, can predispose the offspring to many metabolic and chronic diseases, such as non-alcoholic fatty liver disease, obesity, diabetes, and chronic kidney disease. This review aims to summarize findings from human and animal studies, which support the role of maternal obesity in fetal programing and the potential benefit of altering DNA methylation to limit maternal obesity related disease in the offspring.<\/jats:p>","DOI":"10.3390\/genes12111653","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T21:29:46Z","timestamp":1634765386000},"page":"1653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Aberrant DNA Methylation Mediates the Transgenerational Risk of Metabolic and Chronic Disease Due to Maternal Obesity and Overnutrition"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3020-6424","authenticated-orcid":false,"given":"Yan","family":"Li","sequence":"first","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A.","family":"Pollock","sequence":"additional","affiliation":[{"name":"Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Saad","sequence":"additional","affiliation":[{"name":"Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1564748","DOI":"10.1155\/2018\/1564748","article-title":"Systems and WBANs for Controlling Obesity","volume":"2018","author":"Mohammed","year":"2018","journal-title":"J. Healthc. Eng."},{"key":"ref_2","unstructured":"World Health Organization (2021, June 09). Obesity Data and Statistics. Available online: http:\/\/www.euro.who.int\/en\/health-topics\/noncommunicable-diseases\/obesity\/data-and-statistics."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1136\/oemed-2019-105876","article-title":"Body mass index and the risk of disability retirement: A systematic review and meta-analysis","volume":"77","author":"Shiri","year":"2020","journal-title":"Occup. Environ. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.mce.2015.07.028","article-title":"The impact of maternal obesity during pregnancy on offspring immunity","volume":"418","author":"Wilson","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/S2213-8587(16)30217-0","article-title":"Preconceptional and maternal obesity: Epidemiology and health consequences","volume":"4","author":"Poston","year":"2016","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Igosheva, N., Abramov, A.Y., Poston, L., Eckert, J.J., Fleming, T.P., Duchen, M.R., and McConnell, J. (2010). Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010074"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/obr.12489","article-title":"Maternal body mass index and post-term birth: A systematic review and meta-analysis","volume":"18","author":"Heslehurst","year":"2017","journal-title":"Obes. Rev. Off. J. Int. Assoc. Study Obes."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1136\/eb-2012-100888","article-title":"Excess maternal weight gain during pregnancy is associated with overweight\/obesity in offspring at age 16 years, but maternal pre-pregnancy obesity has a greater effect","volume":"16","author":"Reynolds","year":"2013","journal-title":"Evid. Based Nurs."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e12674","DOI":"10.1111\/aji.12674","article-title":"Maternal obesity and inflammatory mediators: A controversial association","volume":"77","author":"Pendeloski","year":"2017","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1093\/aje\/kwk030","article-title":"Epidemiologic evidence for the fetal overnutrition hypothesis: Findings from the mater-university study of pregnancy and its outcomes","volume":"165","author":"Lawlor","year":"2007","journal-title":"Am. J. Epidemiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1097\/CM9.0000000000000976","article-title":"Early-life nutrition and metabolic disorders in later life: A new perspective on energy metabolism","volume":"133","author":"Zhou","year":"2020","journal-title":"Chin. Med. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"419","DOI":"10.2174\/1389202920666191030092225","article-title":"Maternal Obesity, Maternal Overnutrition and Fetal Programming: Effects of Epigenetic Mechanisms on the Development of Metabolic Disorders","volume":"20","author":"Kabaran","year":"2019","journal-title":"Curr. Genom."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"a019497","DOI":"10.1101\/cshperspect.a019497","article-title":"Epigenetics and Human Disease","volume":"8","author":"Zoghbi","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.jhep.2011.10.018","article-title":"Accumulation of endoplasmic reticulum stress and lipogenesis in the liver through generational effects of high fat diets","volume":"56","author":"Li","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.clp.2014.08.006","article-title":"Fetal programming, epigenetics, and adult onset disease","volume":"41","author":"Lane","year":"2014","journal-title":"Clin. Perinatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1039\/C6CS00599C","article-title":"Epigenetic modification of nucleic acids: From basic studies to medical applications","volume":"46","author":"Chen","year":"2017","journal-title":"Chem. Soc. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5215","DOI":"10.1096\/fj.201800205R","article-title":"DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease","volume":"32","author":"Larkin","year":"2018","journal-title":"Faseb J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"640","DOI":"10.3389\/fgene.2018.00640","article-title":"Epigenetics of Modified DNA Bases: 5-Methylcytosine and Beyond","volume":"9","author":"Kumar","year":"2018","journal-title":"Front. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ymeth.2020.06.021","article-title":"Methods for analysis of specific DNA methylation status","volume":"187","author":"Pajares","year":"2020","journal-title":"Methods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1093\/nar\/8.7.1499","article-title":"DNA methylation and the frequency of CpG in animal DNA","volume":"8","author":"Bird","year":"1980","journal-title":"Nucleic Acids Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/0092-8674(85)90312-5","article-title":"A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA","volume":"40","author":"Bird","year":"1985","journal-title":"Cell"},{"key":"ref_22","first-page":"1821","article-title":"Epigenetics: A new way to look at kidney diseases","volume":"29","author":"Beckerman","year":"2014","journal-title":"Nephrol. Dial. Transplant. Off. Publ. Eur. Dial. Transpl. Assoc. Eur. Ren. Assoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/path.4120","article-title":"The role of promoter hypermethylation in fibroblast activation and fibrogenesis","volume":"229","author":"Zeisberg","year":"2013","journal-title":"J. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nature09165","article-title":"Conserved role of intragenic DNA methylation in regulating alternative promoters","volume":"466","author":"Maunakea","year":"2010","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA methylation and its basic function","volume":"38","author":"Moore","year":"2013","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ren, W., Gao, L., and Song, J. (2018). Structural Basis of DNMT1 and DNMT3A-Mediated DNA Methylation. Genes, 9.","DOI":"10.20944\/preprints201811.0235.v1"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1080\/15592294.2015.1062204","article-title":"Local chromatin microenvironment determines DNMT activity: From DNA methyltransferase to DNA demethylase or DNA dehydroxymethylase","volume":"10","author":"Venkiteswaran","year":"2015","journal-title":"Epigenetics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8905","DOI":"10.1073\/pnas.0501034102","article-title":"Recruitment of DNA methyltransferase I to DNA repair sites","volume":"102","author":"Mortusewicz","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bronner, C., Alhosin, M., Hamiche, A., and Mousli, M. (2019). Coordinated Dialogue between UHRF1 and DNMT1 to Ensure Faithful Inheritance of Methylated DNA Patterns. Genes, 10.","DOI":"10.3390\/genes10010065"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2448","DOI":"10.2174\/1568026619666181120150122","article-title":"DNA Methyltransferase Inhibitors and their Therapeutic Potential","volume":"18","author":"Zhou","year":"2018","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"a019133","DOI":"10.1101\/cshperspect.a019133","article-title":"DNA methylation in mammals","volume":"6","author":"Li","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s12640-014-9497-5","article-title":"A comprehensive view of the epigenetic landscape part I: DNA methylation, passive and active DNA demethylation pathways and histone variants","volume":"27","author":"Kostrzewa","year":"2015","journal-title":"Neurotox. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.cell.2011.08.042","article-title":"DNA demethylation dynamics","volume":"146","author":"Bhutani","year":"2011","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1038\/nature09303","article-title":"Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification","volume":"466","author":"Ito","year":"2010","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.cell.2008.11.042","article-title":"DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45","volume":"135","author":"Rai","year":"2008","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1038\/sj.onc.1210855","article-title":"The interaction of the SRA domain of ICBP90 with a novel domain of DNMT1 is involved in the regulation of VEGF gene expression","volume":"27","author":"Achour","year":"2008","journal-title":"Oncogene"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7258","DOI":"10.1158\/0008-5472.CAN-08-0344","article-title":"Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines","volume":"68","author":"Lopes","year":"2008","journal-title":"Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9883","DOI":"10.1073\/pnas.1817703116","article-title":"DNA methylation analysis and editing in single mammalian oocytes","volume":"116","author":"Wei","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.2337\/diabetes.54.7.1899","article-title":"Nutritional epigenomics of metabolic syndrome: New perspective against the epidemic","volume":"54","author":"Junien","year":"2005","journal-title":"Diabetes"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"791","DOI":"10.4161\/epi.6.7.16209","article-title":"Timing is everything: The when and how of environmentally induced changes in the epigenome of animals","volume":"6","author":"Faulk","year":"2011","journal-title":"Epigenetics"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Josey, M.J., McCullough, L.E., Hoyo, C., and Williams-DeVane, C. (2019). Overall gestational weight gain mediates the relationship between maternal and child obesity. BMC Public Health, 19.","DOI":"10.1186\/s12889-019-7349-1"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"St-Germain, L.E., Castellana, B., Baltayeva, J., and Beristain, A.G. (2020). Maternal Obesity and the Uterine Immune Cell Landscape: The Shaping Role of Inflammation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113776"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7847","DOI":"10.1002\/jcp.27847","article-title":"Effects of obesity and diabetes on the epigenetic modification of mammalian gametes","volume":"234","author":"Ou","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.placenta.2020.02.018","article-title":"Associations between maternal body mass index and diet composition with placental DNA methylation at term","volume":"93","author":"Thakali","year":"2020","journal-title":"Placenta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3109\/07853890.2015.1004360","article-title":"Maternal weight in pregnancy and offspring body composition in late adulthood: Findings from the Helsinki Birth Cohort Study (HBCS)","volume":"47","author":"Eriksson","year":"2015","journal-title":"Ann. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Patel, S., Lawlor, D.A., Callaway, M., Macdonald-Wallis, C., Sattar, N., and Fraser, A. (2016). Association of maternal diabetes\/glycosuria and pre-pregnancy body mass index with offspring indicators of non-alcoholic fatty liver disease. BMC Pediatr., 16.","DOI":"10.1186\/s12887-016-0585-y"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Glastras, S.J., Chen, H., Pollock, C.A., and Saad, S. (2018). Maternal obesity increases the risk of metabolic disease and impacts renal health in offspring. Biosci. Rep., 38.","DOI":"10.1042\/BSR20180050"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mce.2016.07.002","article-title":"Maternal obesity and prenatal programming","volume":"435","author":"Elshenawy","year":"2016","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Li, M., Reynolds, C.M., Sloboda, D.M., Gray, C., and Vickers, M.H. (2013). Effects of taurine supplementation on hepatic markers of inflammation and lipid metabolism in mothers and offspring in the setting of maternal obesity. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076961"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/ijo.2008.213","article-title":"Established maternal obesity in the rat reprograms hypothalamic appetite regulators and leptin signaling at birth","volume":"33","author":"Morris","year":"2009","journal-title":"Int. J. Obes."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1113\/jphysiol.2008.163477","article-title":"Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet","volume":"587","author":"Howie","year":"2009","journal-title":"J. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1017\/S000711450820749X","article-title":"Long-term maternal high-fat feeding from weaning through pregnancy and lactation predisposes offspring to hypertension, raised plasma lipids and fatty liver in mice","volume":"102","author":"Elahi","year":"2009","journal-title":"Br. J. Nutr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e122572","DOI":"10.1172\/jci.insight.122572","article-title":"Gestational diabetes and maternal obesity are associated with epigenome-wide methylation changes in children","volume":"3","author":"Hjort","year":"2018","journal-title":"JCI Insight"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1289\/ehp.1307047","article-title":"DNA methylation in oocytes and liver of female mice and their offspring: Effects of high-fat-diet-induced obesity","volume":"122","author":"Ge","year":"2014","journal-title":"Envrion. Health Perspect."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s13105-011-0084-4","article-title":"Leptin and TNF-\u03b1 promoter methylation levels measured by MSP could predict the response to a low-calorie diet","volume":"67","author":"Cordero","year":"2011","journal-title":"J. Physiol. Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1017\/S0007114515000252","article-title":"Global DNA methylation was changed by a maternal high-lipid, high-energy diet during gestation and lactation in male adult mice liver","volume":"113","author":"Yu","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"29","DOI":"10.2217\/17584299.4.1.29","article-title":"Liver X Receptors as Therapeutic Targets for Managing Cholesterol: Implications for Atherosclerosis and Other Inflammatory Conditions","volume":"4","author":"Zhang","year":"2009","journal-title":"Clin. Lipidol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1194\/jlr.M092593","article-title":"Gene expression and DNA methylation as mechanisms of disturbed metabolism in offspring after exposure to a prenatal HF diet","volume":"60","author":"Rouschop","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.2174\/13816128113199990486","article-title":"Targeting SREBP-1-driven lipid metabolism to treat cancer","volume":"20","author":"Guo","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-981-10-5526-3_3","article-title":"Epigenetic Switching and Neonatal Nutritional Environment","volume":"1012","author":"Hashimoto","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1080\/09637486.2016.1261086","article-title":"Hepatic rhythmicity of endoplasmic reticulum stress is disrupted in perinatal and adult mice models of high-fat diet-induced obesity","volume":"68","author":"Soeda","year":"2017","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1002\/hep4.1265","article-title":"Perinatal Nutritional Reprogramming of the Epigenome Promotes Subsequent Development of Nonalcoholic Steatohepatitis","volume":"2","author":"Tomita","year":"2018","journal-title":"Hepatol. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1210\/en.2006-1115","article-title":"Increased maternal nutrition stimulates peroxisome proliferator activated receptor-\u03b3, adiponectin, and leptin messenger ribonucleic acid expression in adipose tissue before birth","volume":"148","author":"Muhlhausler","year":"2007","journal-title":"Endocrinology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1530\/JOE-16-0037","article-title":"Depot- and sex-specific effects of maternal obesity in offspring\u2019s adipose tissue","volume":"230","author":"Lecoutre","year":"2016","journal-title":"J. Endocrinol."},{"key":"ref_65","first-page":"4148","article-title":"Overweight and CpG methylation of the Pomc promoter in offspring of high-fat-diet-fed dams are not \u201creprogrammed\u201d by regular chow diet in rats","volume":"28","author":"Marco","year":"2014","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1007\/s00125-013-2831-2","article-title":"Nuclear factor \u03baB (NF-\u03baB) suppresses food intake and energy expenditure in mice by directly activating the Pomc promoter","volume":"56","author":"Shi","year":"2013","journal-title":"Diabetologia"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1038\/oby.2008.605","article-title":"Maternal pregestational BMI is associated with methylation of the PPARGC1A promoter in newborns","volume":"17","author":"Gemma","year":"2009","journal-title":"Obesity"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.2337\/db13-0433","article-title":"Maternal obesity induces epigenetic modifications to facilitate Zfp423 expression and enhance adipogenic differentiation in fetal mice","volume":"62","author":"Yang","year":"2013","journal-title":"Diabetes"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4113","DOI":"10.1210\/en.2012-2255","article-title":"Maternal obesity enhances white adipose tissue differentiation and alters genome-scale DNA methylation in male rat offspring","volume":"154","author":"Borengasser","year":"2013","journal-title":"Endocrinology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/j.molmet.2017.08.012","article-title":"Maternal obesity alters fatty acid oxidation, AMPK activity, and associated DNA methylation in mesenchymal stem cells from human infants","volume":"6","author":"Boyle","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Gharipour, M., Barekatain, M., Sung, J., Emami, N., Sadeghian, L., Dianatkhah, M., Sarrafzadegan, N., and Jahanfar, S. (2020). The Epigenetic Overlap between Obesity and Mood Disorders: A Systematic Review. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186758"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1080\/15592294.2019.1581594","article-title":"Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: An epigenome-wide association study","volume":"14","author":"Martin","year":"2019","journal-title":"Epigenetics"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1080\/15592294.2015.1078963","article-title":"Offspring DNA methylation of the aryl-hydrocarbon receptor repressor gene is associated with maternal BMI, gestational age, and birth weight","volume":"10","author":"Burris","year":"2015","journal-title":"Epigenetics"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"158714","DOI":"10.1016\/j.bbalip.2020.158714","article-title":"Potential role of aryl hydrocarbon receptor signaling in childhood obesity","volume":"1865","author":"Shahin","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.abb.2018.01.018","article-title":"Suppressive effects of aryl-hydrocarbon receptor repressor on adipocyte differentiation in 3T3-L1 cells","volume":"642","author":"Ishihara","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e1545","DOI":"10.1542\/peds.2009-2257","article-title":"Hyperglycemia and adverse pregnancy outcome study: Neonatal glycemia","volume":"126","author":"Metzger","year":"2010","journal-title":"Pediatrics"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/oby.21340","article-title":"Differential methylation in inflammation and type 2 diabetes genes in siblings born before and after maternal bariatric surgery","volume":"24","author":"Berglind","year":"2016","journal-title":"Obesity"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1017\/S0007114516003846","article-title":"Epigenetics in type 1 diabetes: TNFa gene promoter methylation status in Chilean patients with type 1 diabetes mellitus","volume":"116","author":"Codner","year":"2016","journal-title":"Br. J. Nutr."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.4049\/jimmunol.1700434","article-title":"Maternal Pregravid Obesity Remodels the DNA Methylation Landscape of Cord Blood Monocytes Disrupting Their Inflammatory Program","volume":"199","author":"Sureshchandra","year":"2017","journal-title":"J. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.2337\/dc10-1024","article-title":"Leptin gene epigenetic adaptation to impaired glucose metabolism during pregnancy","volume":"33","author":"Bouchard","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"654.e1","DOI":"10.1016\/j.ajog.2014.06.037","article-title":"Maternal obesity and gestational diabetes are associated with placental leptin DNA methylation","volume":"211","author":"Lesseur","year":"2014","journal-title":"Am. J. Obs. Gynecol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e1801385","DOI":"10.1002\/mnfr.201801385","article-title":"Resveratrol Treatment Ameliorates Leptin Resistance and Adiposity Programed by the Combined Effect of Maternal and Post-Weaning High-Fat Diet","volume":"63","author":"Yu","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1007\/s00467-018-4005-4","article-title":"Oxidative stress in chronic kidney disease","volume":"34","author":"Daenen","year":"2019","journal-title":"Pediatr. Nephrol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1152\/physiolgenomics.00059.2014","article-title":"In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring","volume":"46","author":"Borengasser","year":"2014","journal-title":"Physiol. Genom."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Borengasser, S.J., Lau, F., Kang, P., Blackburn, M.L., Ronis, M.J., Badger, T.M., and Shankar, K. (2011). Maternal obesity during gestation impairs fatty acid oxidation and mitochondrial SIRT3 expression in rat offspring at weaning. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024068"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"R528","DOI":"10.1152\/ajpregu.00316.2007","article-title":"Maternal obesity at conception programs obesity in the offspring","volume":"294","author":"Shankar","year":"2008","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1210\/en.2010-0017","article-title":"Maternal overweight programs insulin and adiponectin signaling in the offspring","volume":"151","author":"Shankar","year":"2010","journal-title":"Endocrinology"},{"key":"ref_88","first-page":"323","article-title":"Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates","volume":"119","author":"McCurdy","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/ijo.2010.149","article-title":"A systematic review on animal models of maternal high fat feeding and offspring glycaemic control","volume":"35","author":"Ainge","year":"2011","journal-title":"Int. J. Obes."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.1210\/en.2017-00334","article-title":"In Utero Exposure to a High-Fat Diet Programs Hepatic Hypermethylation and Gene Dysregulation and Development of Metabolic Syndrome in Male Mice","volume":"158","author":"Seki","year":"2017","journal-title":"Endocrinology"},{"key":"ref_91","first-page":"E320","article-title":"Identification of the genomic region under epigenetic regulation during non-alcoholic fatty liver disease progression","volume":"48","author":"Hotta","year":"2018","journal-title":"Hepatol. Res. Off. J. Jpn. Soc. Hepatol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Wankhade, U.D., Zhong, Y., Kang, P., Alfaro, M., Chintapalli, S.V., Thakali, K.M., and Shankar, K. (2017). Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet is associated with epigenetic and microbiome alterations. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0175675"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1111\/j.1365-2362.2010.02338.x","article-title":"Increased serum FGF21 levels in patients with nonalcoholic fatty liver disease","volume":"40","author":"Yilmaz","year":"2010","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e1480","DOI":"10.1097\/MD.0000000000001480","article-title":"Epigenetic Modifications in the Biology of Nonalcoholic Fatty Liver Disease: The Role of DNA Hydroxymethylation and TET Proteins","volume":"94","author":"Pirola","year":"2015","journal-title":"Medicine"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/nrendo.2017.91","article-title":"SREBP-regulated lipid metabolism: Convergent physiology\u2014Divergent pathophysiology","volume":"13","author":"Shimano","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1074\/jbc.RA118.005184","article-title":"Thioesterase superfamily member 2 promotes hepatic insulin resistance in the setting of glycerol-3-phosphate acyltransferase 1-induced steatosis","volume":"294","author":"Tillander","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_97","first-page":"1305","article-title":"Maternal high-fat diet disrupted one-carbon metabolism in offspring, contributing to nonalcoholic fatty liver disease","volume":"41","author":"Peng","year":"2021","journal-title":"Liver Int. Off. J. Int. Assoc. Study Liver"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nrm2199","article-title":"Signal integration in the endoplasmic reticulum unfolded protein response","volume":"8","author":"Ron","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s11010-011-1211-9","article-title":"Saturated fatty acid induction of endoplasmic reticulum stress and apoptosis in human liver cells via the PERK\/ATF4\/CHOP signaling pathway","volume":"364","author":"Cao","year":"2012","journal-title":"Mol. Cell. Biochem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.cmet.2012.03.007","article-title":"The role of endoplasmic reticulum in hepatic lipid homeostasis and stress signaling","volume":"15","author":"Fu","year":"2012","journal-title":"Cell Metab."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1053\/j.gastro.2007.10.039","article-title":"Activation and dysregulation of the unfolded protein response in nonalcoholic fatty liver disease","volume":"134","author":"Puri","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1007\/s00125-013-3132-5","article-title":"Exendin-4 is effective against metabolic disorders induced by intrauterine and postnatal overnutrition in rodents","volume":"57","author":"Chen","year":"2014","journal-title":"Diabetologia"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1111\/obr.12524","article-title":"Animal models of maternal high fat diet exposure and effects on metabolism in offspring: A meta-regression analysis","volume":"18","author":"Ribaroff","year":"2017","journal-title":"Obes. Rev. Off. J. Int. Assoc. Study Obes."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1007\/s10654-015-0085-7","article-title":"Maternal obesity during pregnancy and cardiovascular development and disease in the offspring","volume":"30","author":"Gaillard","year":"2015","journal-title":"Eur. J. Epidemiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3565","DOI":"10.1210\/en.2012-1877","article-title":"High-fat intake during pregnancy and lactation exacerbates high-fat diet-induced complications in male offspring in mice","volume":"154","author":"Kruse","year":"2013","journal-title":"Endocrinology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4039","DOI":"10.1210\/en.2010-0098","article-title":"Diet-induced obesity model: Abnormal oocytes and persistent growth abnormalities in the offspring","volume":"151","author":"Jungheim","year":"2010","journal-title":"Endocrinology"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"20110337","DOI":"10.1098\/rstb.2011.0337","article-title":"What obesity research tells us about epigenetic mechanisms","volume":"368","author":"Youngson","year":"2013","journal-title":"Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/em.21827","article-title":"Maternal preconception body mass index and offspring cord blood DNA methylation: Exploration of early life origins of disease","volume":"55","author":"Liu","year":"2014","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.2337\/db11-1314","article-title":"Transgenerational glucose intolerance with Igf2\/H19 epigenetic alterations in mouse islet induced by intrauterine hyperglycemia","volume":"61","author":"Ding","year":"2012","journal-title":"Diabetes"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1002\/mrd.22784","article-title":"Gene expression and epigenetic aberrations in F1-placentas fathered by obese males","volume":"84","author":"Mitchell","year":"2017","journal-title":"Mol. Reprod. Dev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jnutbio.2016.04.005","article-title":"Protective effects of maternal methyl donor supplementation on adult offspring of high fat diet-fed dams","volume":"34","author":"Jiao","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.2337\/db11-0400","article-title":"Maternal environment and the transgenerational cycle of obesity and diabetes","volume":"60","author":"Dabelea","year":"2011","journal-title":"Diabetes"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.2337\/dc06-2559a","article-title":"Maternal obesity and risk of gestational diabetes mellitus","volume":"30","author":"Chu","year":"2007","journal-title":"Diabetes Care"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.2337\/dc08-2077","article-title":"Fetuses of obese mothers develop insulin resistance in utero","volume":"32","author":"Catalano","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_115","first-page":"3786","article-title":"Differential effects of maternal obesity and weight loss in the periconceptional period on the epigenetic regulation of hepatic insulin-signaling pathways in the offspring","volume":"27","author":"Nicholas","year":"2013","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1113\/jphysiol.2009.184168","article-title":"Epigenetic modification of fetal baboon hepatic phosphoenolpyruvate carboxykinase following exposure to moderately reduced nutrient availability","volume":"588","author":"Nijland","year":"2010","journal-title":"J. Physiol."},{"key":"ref_117","first-page":"492170","article-title":"Methylation and expression of immune and inflammatory genes in the offspring of bariatric bypass surgery patients","volume":"2013","author":"Tchernof","year":"2013","journal-title":"J. Obes."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/jmcb\/mjw011","article-title":"Adiponectin, the past two decades","volume":"8","author":"Wang","year":"2016","journal-title":"J. Mol. Cell Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"E365","DOI":"10.1152\/ajpendo.00639.2007","article-title":"Chronic late-gestation hypoglycemia upregulates hepatic PEPCK associated with increased PGC1alpha mRNA and phosphorylated CREB in fetal sheep","volume":"294","author":"Rozance","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/pr.2013.178","article-title":"Impact of maternal overnutrition on gluconeogenic factors and methylation of the phosphoenolpyruvate carboxykinase promoter in the fetal and postnatal liver","volume":"75","author":"Rattanatray","year":"2014","journal-title":"Pediatr. Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"097022","DOI":"10.1289\/EHP1674","article-title":"Sex- and Dose-Specific Effects of Maternal Bisphenol A Exposure on Pancreatic Islets of First- and Second-Generation Adult Mice Offspring","volume":"125","author":"Bansal","year":"2017","journal-title":"Environ. Health Perspect."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/1440-1681.12505","article-title":"The role of maternal nutrition, metabolic function and the placenta in developmental programming of renal dysfunction","volume":"43","author":"Richter","year":"2016","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/nep.13462","article-title":"Maternal obesity and offspring risk of chronic kidney disease","volume":"23","author":"Wong","year":"2018","journal-title":"Nephrology"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/ncpendmet0894","article-title":"The pathogenesis of diabetic nephropathy","volume":"4","author":"Dronavalli","year":"2008","journal-title":"Nat. Clin. Pract. Endocrinol. Metab."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Glastras, S.J., Chen, H., Tsang, M., Teh, R., McGrath, R.T., Zaky, A., Chen, J., Wong, M.G., Pollock, C.A., and Saad, S. (2017). The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172644"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"20","DOI":"10.4161\/epi.6.1.13362","article-title":"DNA methylation profiling identifies epigenetic differences between diabetes patients with ESRD and diabetes patients without nephropathy","volume":"6","author":"Sapienza","year":"2011","journal-title":"Epigenetics"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2174\/1389450116666150113121054","article-title":"ROS-mediated DNA methylation pattern alterations in carcinogenesis","volume":"16","author":"Wu","year":"2015","journal-title":"Curr. Drug Targets"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.3389\/fphar.2019.01192","article-title":"Inflammation in Renal Diseases: New and Old Players","volume":"10","author":"Watanabe","year":"2019","journal-title":"Front. Pharm."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Larkin, B.P., Saad, S., Glastras, S.J., Nguyen, L.T., Hou, M., Chen, H., Wang, R., and Pollock, C.A. (2021). Low-dose hydralazine during gestation reduces renal fibrosis in rodent offspring exposed to maternal high fat diet. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0248854"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.mam.2012.06.010","article-title":"Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives","volume":"34","author":"Milagro","year":"2013","journal-title":"Mol. Asp. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1093\/jn\/128.7.1204","article-title":"Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women","volume":"128","author":"Jacob","year":"1998","journal-title":"J. Nutr."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.orcp.2017.06.004","article-title":"Distinctions in gene-specific changes in DNA methylation in response to folic acid supplementation between women with normal weight and obesity","volume":"11","author":"Park","year":"2017","journal-title":"Obes. Res. Clin. Pract."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2393s","DOI":"10.1093\/jn\/132.8.2393S","article-title":"Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring","volume":"132","author":"Cooney","year":"2002","journal-title":"J. Nutr."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1038\/ijo.2008.100","article-title":"Methyl donor supplementation prevents transgenerational amplification of obesity","volume":"32","author":"Waterland","year":"2008","journal-title":"Int. J. Obes."},{"key":"ref_135","first-page":"949","article-title":"Maternal epigenetics and methyl supplements affect agouti gene expression in Avy\/a mice","volume":"12","author":"Wolff","year":"1998","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1017\/S204017441400035X","article-title":"Supplementation with methyl donors during lactation to high-fat-sucrose-fed dams protects offspring against liver fat accumulation when consuming an obesogenic diet","volume":"5","author":"Cordero","year":"2014","journal-title":"J. Dev. Orig. Health Dis."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s12263-012-0300-z","article-title":"Dietary supplementation with methyl donors reduces fatty liver and modifies the fatty acid synthase DNA methylation profile in rats fed an obesogenic diet","volume":"8","author":"Cordero","year":"2013","journal-title":"Genes Nutr."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/11\/1653\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:19:41Z","timestamp":1760167181000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/11\/1653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,20]]},"references-count":137,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["genes12111653"],"URL":"https:\/\/doi.org\/10.3390\/genes12111653","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,20]]}}}