{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:24:16Z","timestamp":1790681056009,"version":"4.1.0"},"reference-count":139,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T00:00:00Z","timestamp":1575504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004792","name":"Minist\u00e8re de l'Enseignement Sup\u00e9rieur et de la Recherche","doi-asserted-by":"publisher","award":["none"],"award-info":[{"award-number":["none"]}],"id":[{"id":"10.13039\/501100004792","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Metropole Europ\u00e9enne Lilloise","award":["none"],"award-info":[{"award-number":["none"]}]},{"name":"Conseil R\u00e9gional des Hauts-de-France","award":["none"],"award-info":[{"award-number":["none"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Despite constant research and public policy efforts, the obesity epidemic continues to be a major public health threat, and new approaches are urgently needed. It has been shown that nutrient imbalance in early life, from conception to infancy, influences later obesity risk, suggesting that obesity could result from \u201cdevelopmental programming\u201d. In this review, we evaluate the possibility that early postnatal nutrition programs obesity risk via epigenetic mechanisms, especially DNA methylation, focusing on four main topics: (1) the dynamics of epigenetic processes in key metabolic organs during the early postnatal period; (2) the epigenetic effects of alterations in early postnatal nutrition in animal models or breastfeeding in humans; (3) current limitations and remaining outstanding questions in the field of epigenetic programming; (4) candidate pathways by which early postnatal nutrition could epigenetically program adult body weight set point. A particular focus will be given to the potential roles of breast milk fatty acids, neonatal metabolic and hormonal milieu, and gut microbiota. Understanding the mechanisms by which early postnatal nutrition can promote lifelong metabolic modifications is essential to design adequate recommendations and interventions to \u201cde-program\u201d the obesity epidemic.<\/jats:p>","DOI":"10.3390\/nu11122966","type":"journal-article","created":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T03:16:36Z","timestamp":1575515796000},"page":"2966","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Epigenetics: Linking Early Postnatal Nutrition to Obesity Programming?"],"prefix":"10.3390","volume":"11","author":[{"given":"Lucie","family":"Marousez","sequence":"first","affiliation":[{"name":"University Lille, EA4489 Environnement P\u00e9rinatal et Sant\u00e9, \u00c9quipe Malnutrition Maternelle et Programmation des Maladies M\u00e9taboliques, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Lesage","sequence":"additional","affiliation":[{"name":"University Lille, EA4489 Environnement P\u00e9rinatal et Sant\u00e9, \u00c9quipe Malnutrition Maternelle et Programmation des Maladies M\u00e9taboliques, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2211-6146","authenticated-orcid":false,"given":"Delphine","family":"Eberl\u00e9","sequence":"additional","affiliation":[{"name":"University Lille, EA4489 Environnement P\u00e9rinatal et Sant\u00e9, \u00c9quipe Malnutrition Maternelle et Programmation des Maladies M\u00e9taboliques, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,5]]},"reference":[{"key":"ref_1","first-page":"1496","article-title":"Health Effects of Overweight and Obesity in 195 Countries","volume":"377","author":"Afshin","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_2","unstructured":"World Health Organization (2018). Obesity and Overweight, World Health Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"E1195","DOI":"10.1152\/ajpendo.00231.2013","article-title":"Nutritional manipulations in the perinatal period program adipose tissue in offspring","volume":"305","author":"Lukaszewski","year":"2013","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1152\/physrev.00007.2014","article-title":"Gene-environment interactions controlling energy and glucose homeostasis and the developmental origins of obesity","volume":"95","author":"Bouret","year":"2015","journal-title":"Physiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1542\/peds.2004-1176","article-title":"Effect of infant feeding on the risk of obesity across the life course: A quantitative review of published evidence","volume":"115","author":"Owen","year":"2005","journal-title":"Pediatrics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"412S","DOI":"10.3945\/jn.108.097014","article-title":"Impact of infant feeding practices on childhood obesity","volume":"139","author":"Butte","year":"2009","journal-title":"J. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1159\/000365031","article-title":"Early infant feeding and adiposity risk: From infancy to adulthood","volume":"64","author":"Oddy","year":"2014","journal-title":"Ann. Nutr. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.jpeds.2014.02.020","article-title":"Breastfeeding, early nutrition, and adult body fat","volume":"164","author":"Peneau","year":"2014","journal-title":"J. Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/apa.13133","article-title":"Long-term consequences of breastfeeding on cholesterol, obesity, systolic blood pressure and type 2 diabetes: A systematic review and meta-analysis","volume":"104","author":"Horta","year":"2015","journal-title":"Acta Paediatr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S0140-6736(15)01024-7","article-title":"Breastfeeding in the 21st century: Epidemiology, mechanisms, and lifelong effect","volume":"387","author":"Victora","year":"2016","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/ijo.2016.211","article-title":"Early infant adipose deposition is positively associated with the n-6 to n-3 fatty acid ratio in human milk independent of maternal BMI","volume":"41","author":"Rudolph","year":"2017","journal-title":"Int. J. Obes."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1111\/ijpo.12394","article-title":"Bioactive components in human milk are differentially associated with rates of lean and fat mass deposition in infants of mothers with normal vs. elevated BMI","volume":"13","author":"Young","year":"2018","journal-title":"Pediatr. Obes."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1159\/000328040","article-title":"Metabolic programming in the immediate postnatal life","volume":"58","author":"Patel","year":"2011","journal-title":"Ann. Nutr. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.2337\/db11-0957","article-title":"Maternal high-fat diet during gestation or suckling differentially affects offspring leptin sensitivity and obesity","volume":"61","author":"Sun","year":"2012","journal-title":"Diabetes"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"237-e1","DOI":"10.1016\/j.ajog.2014.03.025","article-title":"Maternal obesity and high-fat diet program offspring metabolic syndrome","volume":"211","author":"Desai","year":"2014","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.cell.2014.01.008","article-title":"Neonatal insulin action impairs hypothalamic neurocircuit formation in response to maternal high-fat feeding","volume":"156","author":"Vogt","year":"2014","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1146\/annurev-nutr-071813-105315","article-title":"Epigenetic mechanisms affecting regulation of energy balance: Many questions, few answers","volume":"34","author":"Waterland","year":"2014","journal-title":"Annu. Rev. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin modifications and their function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/S0140-6736(18)31268-6","article-title":"Principles of DNA methylation and their implications for biology and medicine","volume":"392","author":"Dor","year":"2018","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrg.2017.33","article-title":"TET-mediated active DNA demethylation: Mechanism, function and beyond","volume":"18","author":"Wu","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/j.cell.2013.02.004","article-title":"Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives","volume":"152","author":"Spruijt","year":"2013","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8255","DOI":"10.1093\/nar\/gks595","article-title":"Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiation-associated enhancers","volume":"40","author":"Serandour","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Huang, Y., Pastor, W.A., Shen, Y., Tahiliani, M., Liu, D.R., and Rao, A. (2010). The behaviour of 5-hydroxymethylcytosine in bisulfite sequencing. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008888"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nrg3772","article-title":"Advances in the profiling of DNA modifications: Cytosine methylation and beyond","volume":"15","author":"Plongthongkum","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.aninu.2015.09.002","article-title":"Epigenetic modulation of DNA methylation by nutrition and its mechanisms in animals","volume":"1","author":"Zhang","year":"2015","journal-title":"Anim. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kadayifci, F.Z., Zheng, S., and Pan, Y.X. (2018). Molecular Mechanisms Underlying the Link between Diet and DNA Methylation. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19124055"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15212","DOI":"10.1073\/pnas.1205282109","article-title":"Metabolic hypothesis for human altriciality","volume":"109","author":"Dunsworth","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1038\/ijosup.2012.17","article-title":"Nutritional programming of hypothalamic development: Critical periods and windows of opportunity","volume":"2","author":"Bouret","year":"2012","journal-title":"Int. J. Obes. Suppl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.2337\/db12-1306","article-title":"Early postnatal nutrition determines adult physical activity and energy expenditure in female mice","volume":"62","author":"Li","year":"2013","journal-title":"Diabetes"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1007\/s13679-017-0289-0","article-title":"Obesity, Appetite, and the Prefrontal Cortex","volume":"6","author":"Gluck","year":"2017","journal-title":"Curr. Obes. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nature04103","article-title":"Molecular insights into human brain evolution","volume":"437","author":"Hill","year":"2005","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.1093\/cercor\/bhs283","article-title":"Metabolic maturation of the human brain from birth through adolescence: Insights from in vivo magnetic resonance spectroscopy","volume":"23","author":"Bluml","year":"2013","journal-title":"Cereb. Cortex"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.ajhg.2011.12.020","article-title":"DNA methylation signatures in development and aging of the human prefrontal cortex","volume":"90","author":"Numata","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1203\/PDR.0b013e3181df5421","article-title":"Body composition from birth to 4.5 months in infants born to non-obese women","volume":"68","author":"Carberry","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1172\/JCI109295","article-title":"The growth of adipose tissue in children and adolescents. Cross-sectional and longitudinal studies of adipose cell number and size","volume":"63","author":"Knittle","year":"1979","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nature06902","article-title":"Dynamics of fat cell turnover in humans","volume":"453","author":"Spalding","year":"2008","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4709","DOI":"10.1242\/dev.067710","article-title":"Analysis of gene networks in white adipose tissue development reveals a role for ETS2 in adipogenesis","volume":"138","author":"Birsoy","year":"2011","journal-title":"Development"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5027","DOI":"10.1242\/dev.067686","article-title":"The spatiotemporal development of adipose tissue","volume":"138","author":"Han","year":"2011","journal-title":"Development"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1038\/nm.3324","article-title":"Tracking adipogenesis during white adipose tissue development, expansion and regeneration","volume":"19","author":"Wang","year":"2013","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1053\/j.sempedsurg.2013.10.006","article-title":"Neonatal liver physiology","volume":"Volume 22","author":"Grijalva","year":"2013","journal-title":"Seminars in Pediatric Surgery"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1101\/gad.259309.115","article-title":"Gender-specific postnatal demethylation and establishment of epigenetic memory","volume":"29","author":"Reizel","year":"2015","journal-title":"Genes Dev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3701","DOI":"10.1534\/g3.116.034785","article-title":"Extensive Epigenetic Changes Accompany Terminal Differentiation of Mouse Hepatocytes After Birth","volume":"6","author":"Cannon","year":"2016","journal-title":"G3: Genes Genomes Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1038\/s41467-018-04456-6","article-title":"Postnatal DNA demethylation and its role in tissue maturation","volume":"9","author":"Reizel","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.1093\/hmg\/ddp241","article-title":"Epigenomic profiling indicates a role for DNA methylation in early postnatal liver development","volume":"18","author":"Waterland","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"775","DOI":"10.2337\/db14-0158","article-title":"Ligand-activated PPARalpha-dependent DNA demethylation regulates the fatty acid beta-oxidation genes in the postnatal liver","volume":"64","author":"Ehara","year":"2015","journal-title":"Diabetes"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/s41467-018-03038-w","article-title":"Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood","volume":"9","author":"Yuan","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"12418","DOI":"10.1038\/ncomms12418","article-title":"DNA hydroxymethylation controls cardiomyocyte gene expression in development and hypertrophy","volume":"7","author":"Greco","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1038\/nn.2959","article-title":"5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging","volume":"14","author":"Szulwach","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1101\/gad.288035.116","article-title":"Epigenetic regulation of intestinal stem cells by Tet1-mediated DNA hydroxymethylation","volume":"30","author":"Kim","year":"2016","journal-title":"Genes Dev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/s13059-015-0763-5","article-title":"Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation and is guided by the microbiome","volume":"16","author":"Yu","year":"2015","journal-title":"Genome Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1172\/JCI79956","article-title":"DNA methylation directs functional maturation of pancreatic beta cells","volume":"125","author":"Dhawan","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hartwig, F.P., Loret de Mola, C., Davies, N.M., Victora, C.G., and Relton, C.L. (2017). Breastfeeding effects on DNA methylation in the offspring: A systematic literature review. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0175604"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/pr.2013.95","article-title":"Duration of breastfeeding and gender are associated with methylation of the LEPTIN gene in very young children","volume":"74","author":"Eilers","year":"2013","journal-title":"Pediatr. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s13148-019-0727-9","article-title":"Duration of breastfeeding is associated with leptin (LEP) DNA methylation profiles and BMI in 10-year-old children","volume":"11","author":"Sherwood","year":"2019","journal-title":"Clin. Epigenet."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Pauwels, S., Symons, L., Vanautgaerden, E.L., Ghosh, M., Duca, R.C., Bekaert, B., Freson, K., Huybrechts, I., Langie, S.A.S., and Koppen, G. (2019). The Influence of the Duration of Breastfeeding on the Infant\u2019s Metabolic Epigenome. Nutrients, 11.","DOI":"10.3390\/nu11061408"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Houde, A.A., Legare, C., Biron, S., Lescelleur, O., Biertho, L., Marceau, S., Tchernof, A., Vohl, M.C., Hivert, M.F., and Bouchard, L. (2015). Leptin and adiponectin DNA methylation levels in adipose tissues and blood cells are associated with BMI, waist girth and LDL-cholesterol levels in severely obese men and women. BMC Med. Genet., 16.","DOI":"10.1186\/s12881-015-0174-1"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4963","DOI":"10.1113\/jphysiol.2009.176156","article-title":"Hypothalamic proopiomelanocortin promoter methylation becomes altered by early overfeeding: An epigenetic model of obesity and the metabolic syndrome","volume":"587","author":"Plagemann","year":"2009","journal-title":"J. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1515\/jpm.2010.051","article-title":"Epigenetic malprogramming of the insulin receptor promoter due to developmental overfeeding","volume":"38","author":"Plagemann","year":"2010","journal-title":"J. Perinat. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1016\/j.jnutbio.2013.05.002","article-title":"Developmental programming in skeletal muscle in response to overnourishment in the immediate postnatal life in rats","volume":"24","author":"Liu","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6025","DOI":"10.1096\/fj.201700717RR","article-title":"Epigenetic programming at the Mogat1 locus may link neonatal overnutrition with long-term hepatic steatosis and insulin resistance","volume":"32","author":"Pentinat","year":"2018","journal-title":"FASEB J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"dvz015","DOI":"10.1093\/eep\/dvz015","article-title":"Early postnatal overnutrition accelerates aging-associated epigenetic drift in pancreatic islets","volume":"5","author":"Li","year":"2019","journal-title":"Environ. Epigenet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1017\/S2040174413000238","article-title":"Epigenetic changes in hypothalamic appetite regulatory genes may underlie the developmental programming for obesity in rat neonates subjected to a high-carbohydrate dietary modification","volume":"4","author":"Mahmood","year":"2013","journal-title":"J. Dev. Orig. Health Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.jnutbio.2014.05.011","article-title":"Postnatal exposure to a high-carbohydrate diet interferes epigenetically with thyroid hormone receptor induction of the adult male rat skeletal muscle glucose transporter isoform 4 expression","volume":"25","author":"Raychaudhuri","year":"2014","journal-title":"J. Nutr. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"34345","DOI":"10.1038\/srep34345","article-title":"Maternal high-fat diet during lactation impairs thermogenic function of brown adipose tissue in offspring mice","volume":"6","author":"Liang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Butruille, L., Marousez, L., Pourpe, C., Oger, F., Lecoutre, S., Catheline, D., Gors, S., Metges, C.C., Guinez, C., and Laborie, C. (2019). Maternal high-fat diet during suckling programs visceral adiposity and epigenetic regulation of adipose tissue stearoyl-CoA desaturase-1 in offspring. Int. J. Obes.","DOI":"10.1038\/s41366-018-0310-z"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1017\/S0007114511000973","article-title":"Protective effects of leptin during the suckling period against later obesity may be associated with changes in promoter methylation of the hypothalamic pro-opiomelanocortin gene","volume":"106","author":"Palou","year":"2011","journal-title":"Br. J. Nutr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/sj.ijo.0803585","article-title":"The intake of physiological doses of leptin during lactation in rats prevents obesity in later life","volume":"31","author":"Pico","year":"2007","journal-title":"Int. J. Obes."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.abb.2018.05.009","article-title":"Dietary vitamin A impacts DNA methylation patterns of adipogenesis-related genes in suckling rats","volume":"650","author":"Arreguin","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1038\/ijo.2012.190","article-title":"Vitamin A supplementation in early life affects later response to an obesogenic diet in rats","volume":"37","author":"Granados","year":"2013","journal-title":"Int. J. Obes."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"337","DOI":"10.33549\/physiolres.931939","article-title":"Developmental changes in gut microbiota and enzyme activity predict obesity risk in rats arising from reduced nests","volume":"60","author":"Sefcikova","year":"2011","journal-title":"Physiol. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e20170971","DOI":"10.1590\/0001-3765201920170971","article-title":"Litter Size Reduction Induces Metabolic and Histological Adjustments in Dams throughout Lactation with Early Effects on Offspring","volume":"91","author":"Xavier","year":"2019","journal-title":"An. Acad. Bras. Ci\u00eancias"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1007\/s10545-008-1033-4","article-title":"Metabolic programming: Role of nutrition in the immediate postnatal life","volume":"32","author":"Patel","year":"2009","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1210\/en.2009-1295","article-title":"Early overnutrition results in early-onset arcuate leptin resistance and increased sensitivity to high-fat diet","volume":"151","author":"Glavas","year":"2010","journal-title":"Endocrinology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"553","DOI":"10.3945\/jn.112.172825","article-title":"Postnatal overfeeding in rodents by litter size reduction induces major short- and long-term pathophysiological consequences","volume":"143","author":"Habbout","year":"2013","journal-title":"J. Nutr."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1038\/s41366-018-0094-1","article-title":"Maternal overnutrition programs epigenetic changes in the regulatory regions of hypothalamic Pomc in the offspring of rats","volume":"42","author":"Allen","year":"2018","journal-title":"Int. J. Obes."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5348","DOI":"10.1210\/en.2008-0582","article-title":"Maternal and postnatal overnutrition differentially impact appetite regulators and fuel metabolism","volume":"149","author":"Chen","year":"2008","journal-title":"Endocrinology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1097\/WNR.0b013e32805dfb93","article-title":"Insulin resistance of hypothalamic arcuate neurons in neonatally overfed rats","volume":"18","author":"Davidowa","year":"2007","journal-title":"Neuroreport"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s12944-015-0094-2","article-title":"Long-term effect of early postnatal overnutrition on insulin resistance and serum fatty acid profiles in male rats","volume":"14","author":"Bei","year":"2015","journal-title":"Lipids Health Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s12015-018-9812-2","article-title":"Neonatal overfeeding impairs differentiation potential of mice subcutaneous adipose mesenchymal stem cells","volume":"14","author":"Dias","year":"2018","journal-title":"Stem Cell Rev."},{"key":"ref_81","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_82","doi-asserted-by":"crossref","first-page":"4453","DOI":"10.1113\/JP272123","article-title":"Maternal obesity epigenetically alters visceral fat progenitor cell properties in male offspring mice","volume":"594","author":"Liang","year":"2016","journal-title":"J. Physiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/nm0410-400","article-title":"Diacylglycerol-mediated insulin resistance","volume":"16","author":"Erion","year":"2010","journal-title":"Nat. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5617","DOI":"10.1210\/en.2010-0684","article-title":"Transgenerational inheritance of glucose intolerance in a mouse model of neonatal overnutrition","volume":"151","author":"Pentinat","year":"2010","journal-title":"Endocrinology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1111\/jne.12281","article-title":"Neonatal Overfeeding in Female Mice Predisposes the Development of Obesity in their Male Offspring via Altered Central Leptin Signalling","volume":"27","author":"Wang","year":"2015","journal-title":"J. Neuroendocrinol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1093\/jn\/132.3.357","article-title":"Early postnatal nutrition determines adult pancreatic glucose-responsive insulin secretion and islet gene expression in rats","volume":"132","author":"Waterland","year":"2002","journal-title":"J. Nutr."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1126\/science.1198116","article-title":"Weaning and growth of artificially reared rats","volume":"190","author":"Hall","year":"1975","journal-title":"Science"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/jn\/122.3.412","article-title":"Artificial-rearing technique: Its usefulness in nutrition research","volume":"122","author":"Patel","year":"1992","journal-title":"J. Nutr."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1203\/01.PDR.0000132753.81333.39","article-title":"Artificial rearing of mouse pups: Development of a mouse pup in a cup model","volume":"56","author":"Beierle","year":"2004","journal-title":"Pediatr. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1074\/jbc.R100017200","article-title":"Metabolic programming: Causes and consequences","volume":"277","author":"Patel","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1177\/153537020322800102","article-title":"Neonatal nutrition: Metabolic programming of pancreatic islets and obesity","volume":"228","author":"Srinivasan","year":"2003","journal-title":"Exp. Biol. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1677\/JOE-08-0021","article-title":"A high-carbohydrate diet in the immediate postnatal life of rats induces adaptations predisposing to adult-onset obesity","volume":"197","author":"Srinivasan","year":"2008","journal-title":"J. Endocrinol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1051\/rnd:19860413","article-title":"Changes in energy metabolism during the suckling and weaning period in the newborn","volume":"26","author":"Ferre","year":"1986","journal-title":"Reprod. Nutr. Dev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0014-5793(74)80006-2","article-title":"The activity of pyruvate dehydrogenase in rat brain during postnatal development","volume":"39","author":"Cremer","year":"1974","journal-title":"FEBS Lett."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"E895","DOI":"10.1152\/ajpendo.90460.2008","article-title":"Maternal obesity and fetal programming: Effects of a high-carbohydrate nutritional modification in the immediate postnatal life of female rats","volume":"295","author":"Srinivasan","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"R768","DOI":"10.1152\/ajpregu.00138.2006","article-title":"Postnatal environment overrides genetic and prenatal factors influencing offspring obesity and insulin resistance","volume":"291","author":"Gorski","year":"2006","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.jhep.2009.12.042","article-title":"Maternal obesity during pregnancy and lactation programs the development of offspring non-alcoholic fatty liver disease in mice","volume":"52","author":"Oben","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1017\/S2040174413000548","article-title":"Short- and long-term effects of maternal perinatal undernutrition are lowered by cross-fostering during lactation in the male rat","volume":"5","author":"Wattez","year":"2014","journal-title":"J. Dev. Orig. Health Dis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3969","DOI":"10.1113\/jphysiol.2011.212324","article-title":"Fostering in mice induces cardiovascular and metabolic dysfunction in adulthood","volume":"589","author":"Matthews","year":"2011","journal-title":"J. Physiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3177\/jnsv.59.384","article-title":"High dietary fat intake during lactation promotes development of diet-induced obesity in male offspring of mice","volume":"59","author":"Tsuduki","year":"2013","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3457","DOI":"10.1096\/fj.201701154R","article-title":"Impaired prolactin actions mediate altered offspring metabolism induced by maternal high-fat feeding during lactation","volume":"32","author":"Clapp","year":"2018","journal-title":"FASEB J."},{"key":"ref_102","first-page":"875","article-title":"Leptin as a breast milk component for the prevention of obesity","volume":"76","author":"Palou","year":"2018","journal-title":"Nutr. Rev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.1210\/jcem.82.12.4590","article-title":"Presence of leptin in colostrum and\/or breast milk from lactating mothers: A potential role in the regulation of neonatal food intake","volume":"82","author":"Casabiell","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"E15","DOI":"10.1542\/peds.108.1.e15","article-title":"Leptin levels in preterm human breast milk and infant formula","volume":"108","author":"Resto","year":"2001","journal-title":"Pediatrics"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1210\/en.2005-0112","article-title":"Leptin orally supplied to neonate rats is directly uptaken by the immature stomach and may regulate short-term feeding","volume":"146","author":"Sanchez","year":"2005","journal-title":"Endocrinology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1210\/en.2007-0630","article-title":"Oral supplementation with physiological doses of leptin during lactation in rats improves insulin sensitivity and affects food preferences later in life","volume":"149","author":"Sanchez","year":"2008","journal-title":"Endocrinology"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/ijo.2010.18","article-title":"Leptin intake during the suckling period improves the metabolic response of adipose tissue to a high-fat diet","volume":"34","author":"Priego","year":"2010","journal-title":"Int. J. Obes."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.appet.2008.09.013","article-title":"Leptin intake during lactation prevents obesity and affects food intake and food preferences in later life","volume":"52","author":"Palou","year":"2009","journal-title":"Appetite"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/oby.2008.57","article-title":"Neonatal exposure to leptin augments diet-induced obesity in leptin-deficient Ob\/Ob mice","volume":"16","author":"Yura","year":"2008","journal-title":"Obesity"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.cmet.2005.05.005","article-title":"Role of premature leptin surge in obesity resulting from intrauterine undernutrition","volume":"1","author":"Yura","year":"2005","journal-title":"Cell Metab."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1055\/s-2002-33473","article-title":"Leptin treatment during the neonatal period is associated with higher food intake and adult body weight in rats","volume":"34","author":"Teixeira","year":"2002","journal-title":"Horm. Metab. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1210\/en.2007-0981","article-title":"The effect of neonatal leptin treatment on postnatal weight gain in male rats is dependent on maternal nutritional status during pregnancy","volume":"149","author":"Vickers","year":"2008","journal-title":"Endocrinology"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e1800463","DOI":"10.1002\/mnfr.201800463","article-title":"Programming of the Beige Phenotype in White Adipose Tissue of Adult Mice by Mild Resveratrol and Nicotinamide Riboside Supplementations in Early Postnatal Life","volume":"62","author":"Serrano","year":"2018","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"126","DOI":"10.3389\/fphar.2019.00126","article-title":"Making Sense of the Epigenome Using Data Integration Approaches","volume":"10","author":"Cazaly","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1289\/EHP595","article-title":"Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children\u2019s Environmental Health Studies: The Children\u2019s Environmental Health and Disease Prevention Research Center\u2019s Epigenetics Working Group","volume":"125","author":"Breton","year":"2017","journal-title":"Environ. Health Perspect."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s13148-016-0256-8","article-title":"DNA methylation: Conducting the orchestra from exposure to phenotype?","volume":"8","author":"Leenen","year":"2016","journal-title":"Clin. Epigenet."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.cell.2016.08.056","article-title":"Editing DNA Methylation in the Mammalian Genome","volume":"167","author":"Liu","year":"2016","journal-title":"Cell"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/j.1740-8709.2011.00318.x","article-title":"Metabolic programming of long-term outcomes due to fatty acid nutrition in early life","volume":"7","author":"Innis","year":"2011","journal-title":"Matern. Child Nutr."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1097\/MED.0b013e32835c1ba7","article-title":"Omega-6 polyunsaturated fatty acids and the early origins of obesity","volume":"20","author":"Muhlhausler","year":"2013","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1159\/000152921","article-title":"Omega-6 fatty acids and excessive adipose tissue development","volume":"98","author":"Ailhaud","year":"2008","journal-title":"World Rev. Nutr. Diet."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/MOL.0b013e3282ffaf6a","article-title":"N-3 polyunsaturated fatty acid regulation of hepatic gene transcription","volume":"19","author":"Jump","year":"2008","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1080\/15592294.2016.1161873","article-title":"Arachidonic and oleic acid exert distinct effects on the DNA methylome","volume":"11","author":"Vaquero","year":"2016","journal-title":"Epigenetics"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"991","DOI":"10.3945\/ajcn.116.143164","article-title":"Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: A randomized controlled trial","volume":"105","author":"Perfilyev","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1038\/ncomms3262","article-title":"PPARgamma-induced PARylation promotes local DNA demethylation by production of 5-hydroxymethylcytosine","volume":"4","author":"Fujiki","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"7186","DOI":"10.4049\/jimmunol.1001437","article-title":"Peroxisome proliferator-activated receptor alpha and gamma agonists together with TGF-beta convert human CD4+CD25- T cells into functional Foxp3+ regulatory T cells","volume":"185","author":"Lei","year":"2010","journal-title":"J. Immunol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"461784","DOI":"10.1155\/2012\/461784","article-title":"Correlations among PPARgamma, DNMT1, and DNMT3B Expression Levels and Pancreatic Cancer","volume":"2012","author":"Pazienza","year":"2012","journal-title":"PPAR Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"487","DOI":"10.4161\/epi.4.7.9883","article-title":"Dnmt3\/transcription factor interactions as crucial players in targeted DNA methylation","volume":"4","author":"Hervouet","year":"2009","journal-title":"Epigenetics"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1177\/1947601910373794","article-title":"Dnmt1\/Transcription factor interactions: An alternative mechanism of DNA methylation inheritance","volume":"1","author":"Hervouet","year":"2010","journal-title":"Genes Cancer"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"296368","DOI":"10.1155\/2012\/296368","article-title":"Analysis of insulin in human breast milk in mothers with type 1 and type 2 diabetes mellitus","volume":"2012","author":"Whitmore","year":"2012","journal-title":"Int. J. Endocrinol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.molmet.2018.04.007","article-title":"Sex and gender differences in developmental programming of metabolism","volume":"15","author":"Dearden","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3389\/fendo.2014.00155","article-title":"O-GlcNAcylation, an Epigenetic Mark. Focus on the Histone Code, TET Family Proteins, and Polycomb Group Proteins","volume":"5","author":"Dehennaut","year":"2014","journal-title":"Front. Endocrinol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"E11033","DOI":"10.1073\/pnas.1805397115","article-title":"Combinatorial regulation of hepatic cytoplasmic signaling and nuclear transcriptional events by the OGT\/REV-ERBalpha complex","volume":"115","author":"Berthier","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.3945\/ajcn.115.115451","article-title":"Associations between human milk oligosaccharides and infant body composition in the first 6 mo of life","volume":"102","author":"Alderete","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Gridneva, Z., Rea, A., Tie, W.J., Lai, C.T., Kugananthan, S., Ward, L.C., Murray, K., Hartmann, P.E., and Geddes, D.T. (2019). Carbohydrates in Human Milk and Body Composition of Term Infants during the First 12 Months of Lactation. Nutrients, 11.","DOI":"10.3390\/nu11071472"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.3390\/nu7042237","article-title":"The infant gut microbiome: Evidence for obesity risk and dietary intervention","volume":"7","author":"Koleva","year":"2015","journal-title":"Nutrients"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1007\/s13668-018-0248-8","article-title":"Role of Gut Microbiota-Generated Short-Chain Fatty Acids in Metabolic and Cardiovascular Health","volume":"7","author":"Chambers","year":"2018","journal-title":"Curr. Nutr. Rep."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1093\/jn\/nxy320","article-title":"Human Milk Short-Chain Fatty Acid Composition is Associated with Adiposity Outcomes in Infants","volume":"149","author":"Prentice","year":"2019","journal-title":"J. Nutr."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"638","DOI":"10.3389\/fgene.2019.00638","article-title":"Epigenetic Regulation at the Interplay Between Gut Microbiota and Host Metabolism","volume":"10","author":"Yanes","year":"2019","journal-title":"Front. Genet."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13073-018-0534-5","article-title":"Exposure to the gut microbiota drives distinct methylome and transcriptome changes in intestinal epithelial cells during postnatal development","volume":"10","author":"Pan","year":"2018","journal-title":"Genome Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/12\/2966\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:40:21Z","timestamp":1760190021000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/12\/2966"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,5]]},"references-count":139,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["nu11122966"],"URL":"https:\/\/doi.org\/10.3390\/nu11122966","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,5]]}}}