{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T22:29:03Z","timestamp":1777674543030,"version":"3.51.4"},"reference-count":60,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T00:00:00Z","timestamp":1705449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00399"],"award-info":[{"award-number":["PI20\/00399"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00451"],"award-info":[{"award-number":["PI19\/00451"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/00366"],"award-info":[{"award-number":["PI22\/00366"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Limited nutrient supply to the fetus results in physiologic and metabolic adaptations that have unfavorable consequences in the offspring. In a swine animal model, we aimed to study the effects of gestational caloric restriction and early postnatal metformin administration on offspring\u2019s adipose tissue epigenetics and their association with morphometric and metabolic variables. Sows were either underfed (30% restriction of total food) or kept under standard diet during gestation, and piglets were randomly assigned at birth to receive metformin (n = 16 per group) or vehicle treatment (n = 16 per group) throughout lactation. DNA methylation and gene expression were assessed in the retroperitoneal adipose tissue of piglets at weaning. Results showed that gestational caloric restriction had a negative effect on the metabolic profile of the piglets, increased the expression of inflammatory markers in the adipose tissue, and changed the methylation of several genes related to metabolism. Metformin treatment resulted in positive changes in the adipocyte morphology and regulated the methylation of several genes related to atherosclerosis, insulin, and fatty acids signaling pathways. The methylation and gene expression of the differentially methylated FASN, SLC5A10, COL5A1, and PRKCZ genes in adipose tissue associated with the metabolic profile in the piglets born to underfed sows. In conclusion, our swine model showed that caloric restriction during pregnancy was associated with impaired inflammatory and DNA methylation markers in the offspring\u2019s adipose tissue that could predispose the offspring to later metabolic abnormalities. Early metformin administration could modulate the size of adipocytes and the DNA methylation changes.<\/jats:p>","DOI":"10.3390\/ijms25021128","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T07:41:28Z","timestamp":1705477288000},"page":"1128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Gestational Caloric Restriction Alters Adipose Tissue Methylome and Offspring\u2019s Metabolic Profile in a Swine Model"],"prefix":"10.3390","volume":"25","author":[{"given":"Berta","family":"Mas-Par\u00e9s","sequence":"first","affiliation":[{"name":"Obesity and Cardiovascular Risk in Pediatrics, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00edlvia","family":"Xargay-Torrent","sequence":"additional","affiliation":[{"name":"Obesity and Cardiovascular Risk in Pediatrics, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma","family":"Carreras-Badosa","sequence":"additional","affiliation":[{"name":"Obesity and Cardiovascular Risk in Pediatrics, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8183-5218","authenticated-orcid":false,"given":"Ariadna","family":"G\u00f3mez-Vilarrubla","sequence":"additional","affiliation":[{"name":"Materno-Fetal Metabolic Research, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Niub\u00f3-Pall\u00e0s","sequence":"additional","affiliation":[{"name":"Materno-Fetal Metabolic Research, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Tibau","sequence":"additional","affiliation":[{"name":"Benestar Animal, Institut de Recerca i Tecnolog\u00eda Agroaliment\u00e0ries (IRTA), 17121 Monells, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep","family":"Reixach","sequence":"additional","affiliation":[{"name":"Selecci\u00f3 Batall\u00e9, 17421 Riudarenes, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5253-3808","authenticated-orcid":false,"given":"Anna","family":"Prats-Puig","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, EUSES, University of Girona, 17190 Salt, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"de Zegher","sequence":"additional","affiliation":[{"name":"Department of Development and Regeneration, University of Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lourdes","family":"Iba\u00f1ez","sequence":"additional","affiliation":[{"name":"Endocrinology, Fundaci\u00f3 Sant Joan de D\u00e9u, University of Barcelona, 08950 Esplugues de Llobregat, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), ISCIII, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8821-6655","authenticated-orcid":false,"given":"Judit","family":"Bassols","sequence":"additional","affiliation":[{"name":"Materno-Fetal Metabolic Research, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abel","family":"L\u00f3pez-Bermejo","sequence":"additional","affiliation":[{"name":"Obesity and Cardiovascular Risk in Pediatrics, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain"},{"name":"Pediatrics, Hospital Dr. Josep Trueta, 17007 Girona, Spain"},{"name":"Department of Medical Sciences, University of Girona, 17820 Girona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R111","DOI":"10.1530\/REP-14-0334","article-title":"Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment","volume":"148","author":"Schneider","year":"2014","journal-title":"Reproduction"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/BF00399095","article-title":"Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): Relation to reduced fetal growth","volume":"36","author":"Barker","year":"1993","journal-title":"Diabetologia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1017\/CBO9780511544699.035","article-title":"Developmental origins of health and disease: Public-health perspectives","volume":"353","author":"Law","year":"2006","journal-title":"Dev. Orig. Health Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s40572-018-0217-9","article-title":"Adverse Maternal Metabolic Intrauterine Environment and Placental Epigenetics: Implications for Fetal Metabolic Programming","volume":"5","author":"Lesseur","year":"2018","journal-title":"Curr. Environ. Health Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e363","DOI":"10.1542\/neo.23-6-e363","article-title":"Fetal Growth and Intrauterine Epigenetic Programming of Obesity and Cardiometabolic Disease","volume":"23","author":"Harary","year":"2022","journal-title":"Neoreviews"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.beem.2012.03.010","article-title":"Maternal obesity, gestational weight gain and diet as determinants of offspring long term health","volume":"26","author":"Poston","year":"2012","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Fall, C.H.D., and Kumaran, K. (2019). Metabolic programming in early life in humans. Philos. Trans. R. Soc. B Biol. Sci., 374.","DOI":"10.1098\/rstb.2018.0123"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e000285","DOI":"10.1136\/lupus-2018-000285","article-title":"DNA methylation 101: What is important to know about DNA methylation and its role in SLE risk and disease heterogeneity","volume":"25","author":"Lanata","year":"2018","journal-title":"Lupus Sci\/ Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ji, Y., Wu, Z., Dai, Z., Wang, X., Li, J., Wang, B., and Wu, G. (2017). Fetal and neonatal programming of postnatal growth and feed efficiency in swine. J. Anim. Sci. Biotechnol., 8.","DOI":"10.1186\/s40104-017-0173-5"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1080\/10408363.2017.1422109","article-title":"Maternal obesity, diabetes during pregnancy and epigenetic mechanisms that influence the developmental origins of cardiometabolic disease in the offspring","volume":"55","author":"Agarwal","year":"2018","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1017\/S0007114513002948","article-title":"Prenatal programming in an obese swine model: Sex-related effects of maternal energy restriction on morphology, metabolism and hypothalamic gene expression","volume":"111","author":"Ayuso","year":"2014","journal-title":"Br. J. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Orsso, C.E., Colin-Ramirez, E., Field, C.J., Madsen, K.L., Prado, C.M., and Haqq, A.M. (2020). Adipose tissue development and expansion from the womb to adolescence: An overview. Nutrients, 12.","DOI":"10.3390\/nu12092735"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1677\/joe.0.1790293","article-title":"Endocrine and nutritional regulation of fetal adipose tissue development","volume":"179","author":"Symonds","year":"2003","journal-title":"J. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3943","DOI":"10.1210\/en.2005-0246","article-title":"Maternal nutritional programming of fetal adipose tissue development: Differential effects on mRNA abundance for uncoupling proteins, peroxisome proliferator activated and prolactin receptors","volume":"146","author":"Bispham","year":"2005","journal-title":"Endocrinology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1079\/PNS2004370","article-title":"Prenatal programming of postnatal obesity: Fetal nutrition and the regulation of leptin synthesis and secretion before birth","volume":"63","author":"McMillen","year":"2004","journal-title":"Proc. Nutr. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.placenta.2010.07.014","article-title":"Maternal undernutrition alters fat cell size distribution, but not lipogenic gene expression, in the visceral fat of the late gestation guinea pig fetus","volume":"31","author":"Nguyen","year":"2010","journal-title":"Placenta"},{"key":"ref_17","unstructured":"Soliman, A., De Sanctis, V., Alaaraj, N., and Hamed, N. (2020). The clinical application of metformin in children and adolescents: A short update. Acta Biomed., 91."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s00125-017-4342-z","article-title":"The mechanisms of action of metformin","volume":"60","author":"Rena","year":"2017","journal-title":"Diabetologia"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Garcia-Contreras, C., Vazquez-Gomez, M., Pesantez-Pacheco, J.L., Torres-Rovira, L., Heras-Molina, A., Encinas, T., Astiz, S., and Gonzalez-Bulnes, A. (2019). Maternal metformin treatment improves developmental and metabolic traits of IUGR fetuses. Biomolecules, 9.","DOI":"10.3390\/biom9050166"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.jadohealth.2017.04.010","article-title":"Normalizing Ovulation Rate by Preferential Reduction of Hepato-Visceral Fat in Adolescent Girls With Polycystic Ovary Syndrome","volume":"61","author":"Sebastiani","year":"2017","journal-title":"J. Adolesc. Health"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1111\/pedi.12220","article-title":"Metformin treatment to reduce central adiposity after prenatal growth restraint: A placebo-controlled pilot study in prepubertal children","volume":"16","author":"Bassols","year":"2015","journal-title":"Pediatr. Diabetes"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bassols, J., Mart\u00ednez-Calcerrada, J.-M., Osiniri, I., D\u00edaz-Rold\u00e1n, F., Xargay-Torrent, S., Mas-Par\u00e9s, B., Dorado-Ceballos, E., Prats-Puig, A., Carreras-Badosa, G., and de Zegher, F. (2019). Effects of metformin administration on endocrine-metabolic parameters, visceral adiposity and cardiovascular risk factors in children with obesity and risk markers for metabolic syndrome: A pilot study. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0226303"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/s41366-022-01076-5","article-title":"Metabolic programming in the offspring after gestational overfeeding in the mother: Toward neonatal rescuing with metformin in a swine model","volume":"46","author":"Tibau","year":"2022","journal-title":"Int. J. Obes."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1242\/jcs.104992","article-title":"A comparative perspective on lipid storage in animals","volume":"126","author":"Birsoy","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4727","DOI":"10.1113\/JP271745","article-title":"Programming of maternal and offspring disease: Impact of growth restriction, fetal sex and transmission across generations","volume":"594","author":"Cheong","year":"2016","journal-title":"J. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1111\/j.1549-8719.2011.00089.x","article-title":"Intrauterine Growth Restriction and Developmental Programming of the Metabolic Syndrome: A Critical Appraisal","volume":"18","author":"Neitzke","year":"2011","journal-title":"Microcirculation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"534","DOI":"10.3177\/jnsv.65.534","article-title":"Undernutrition in pregnant rats induces glucose intolerance with enhanced expression of inflammation-related genes in peripheral leukocytes of the offspring","volume":"65","author":"Jin","year":"2019","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1007\/s00125-016-3983-7","article-title":"DNA hypermethylation of CD3+ T cells from cord blood of infants exposed to intrauterine growth restriction","volume":"59","author":"Williams","year":"2016","journal-title":"Diabetologia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e14359","DOI":"10.14814\/phy2.14359","article-title":"Differential impacts of late gestational over\u2013and undernutrition on adipose tissue traits and associated visceral obesity risk upon exposure to a postnatal high-fat diet in adolescent sheep","volume":"8","author":"Khanal","year":"2020","journal-title":"Physiol. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1017\/S0007114512004199","article-title":"Late gestation undernutrition can predispose for visceral adiposity by altering fat distribution patterns and increasing the preference for a high-fat diet in early postnatal life","volume":"109","author":"Nielsen","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/s41419-022-04752-6","article-title":"Adipose tissue aging: Mechanisms and therapeutic implications","volume":"13","author":"Ou","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Szkudelski, T., Konieczna, K., and Szkudelska, K. (2022). Regulatory Effects of Metformin, an Antidiabetic Biguanide Drug, on the Metabolism of Primary Rat Adipocytes. Molecules, 27.","DOI":"10.3390\/molecules27165250"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"116682","DOI":"10.1016\/j.lfs.2019.116682","article-title":"Metformin reduces fibrosis factors in insulin resistant and hypertrophied adipocyte via integrin\/ERK, collagen VI, apoptosis, and necrosis reduction","volume":"233","author":"Teimourian","year":"2019","journal-title":"Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e12723","DOI":"10.1111\/acel.12723","article-title":"Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults","volume":"17","author":"Kulkarni","year":"2018","journal-title":"Aging Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"E600","DOI":"10.1152\/ajpendo.00473.2019","article-title":"Lactational metformin exposure programs offspring white adipose tissue glucose homeostasis and resilience to metabolic stress in a sex-dependent manner","volume":"318","author":"Carlson","year":"2020","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e88080","DOI":"10.7554\/eLife.88080","article-title":"The effects of caloric restriction on adipose tissue and metabolic health are sex-and age-dependent","volume":"12","author":"Suchacki","year":"2023","journal-title":"eLife"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"110875","DOI":"10.1016\/j.exger.2020.110875","article-title":"Impact of calorie restriction on energy metabolism in humans","volume":"133","author":"Most","year":"2020","journal-title":"Exp. Gerontol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1210\/er.2017-00211","article-title":"Metabolic flexibility as an adaptation to energy resources and requirements in health and disease","volume":"39","author":"Smith","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/s41574-023-00833-4","article-title":"Metformin: Update on mechanisms of action and repurposing potential","volume":"19","author":"Foretz","year":"2023","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, Y., Ma, C., Sun, Y., Li, Y., Kang, L., and Jiang, Y. (2017). Dynamic transcriptome and DNA methylome analyses on longissimus dorsi to identify genes underlying intramuscular fat content in pigs. BMC Genom., 18.","DOI":"10.1186\/s12864-017-4201-9"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1743-7075-7-3","article-title":"Inverse relation between FASN expression in human adipose tissue and the insulin resistance level","volume":"7","author":"Mayas","year":"2010","journal-title":"Nutr. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.febslet.2011.12.027","article-title":"Functional characterisation of human SGLT-5 as a novel kidney-specific sodium-dependent sugar transporter","volume":"586","author":"Grempler","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Fukuzawa, T., Fukazawa, M., Ueda, O., Shimada, H., Kito, A., Kakefuda, M., Kawase, Y., Wada, N.A., Goto, C., and Fukushima, N. (2013). SGLT5 Reabsorbs Fructose in the Kidney but Its Deficiency Paradoxically Exacerbates Hepatic Steatosis Induced by Fructose. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0056681"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00018-023-04884-8","article-title":"SGLT5 is the renal transporter for 1,5-anhydroglucitol, a major player in two rare forms of neutropenia","volume":"80","author":"Diederich","year":"2023","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4363","DOI":"10.1073\/pnas.1416412112","article-title":"Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue","volume":"112","author":"Minchin","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Dankel, S.N., Fadnes, D.J., Stavrum, A.-K., Stansberg, C., Holdhus, R., Hoang, T., Veum, V.L., Christensen, B.J., V\u00e5ge, V., and Sagen, J.V. (2010). Switch from stress response to homeobox transcription factors in adipose tissue after profound fat loss. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011033"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"25157","DOI":"10.1074\/jbc.M402477200","article-title":"Protein kinase C-\u03b6-induced phosphorylation of Ser 318 in insulin receptor substrate-1 (IRS-1) attenuates the interaction with the insulin receptor and the tyrosine phosphorylation of IRS-1","volume":"279","author":"Moeschel","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"721493","DOI":"10.1155\/2013\/721493","article-title":"Hypermethylation of the PRKCZ gene in type 2 diabetes mellitus","volume":"2013","author":"Zou","year":"2013","journal-title":"J. Diabetes Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Poore, K.R., Hollis, L.J., Murray, R.J.S., Warlow, A., Brewin, A., Fulford, L., Cleal, J.K., Lillycrop, K.A., Burdge, G.C., and Hanson, M.A. (2014). Differential pathways to adult metabolic dysfunction following poor nutrition at two critical developmental periods in sheep. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090994"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"16073","DOI":"10.1096\/fj.202000985RR","article-title":"Maternal food restriction-induced intrauterine growth restriction in a rat model leads to sex-specific adipogenic programming","volume":"34","author":"Sreekantha","year":"2020","journal-title":"FASEB J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/s41390-019-0428-2","article-title":"Dlk1 expression relates to visceral fat expansion and insulin resistance in male and female rats with postnatal catch-up growth","volume":"86","author":"Remesar","year":"2019","journal-title":"Pediatr. Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Garcia-Contreras, C., Vazquez-Gomez, M., Pesantez-Pacheco, J.L., Heras-Molina, A., Encinas, T., Astiz, S., and Gonzalez-Bulnes, A. (2020). The effects of maternal metformin treatment on late prenatal and early postnatal development of the offspring are modulated by sex. Pharmaceuticals, 13.","DOI":"10.3390\/ph13110363"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.earlhumdev.2006.07.001","article-title":"The Dutch famine and its long-term consequences for adult health","volume":"82","author":"Roseboom","year":"2006","journal-title":"Early Hum. Dev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1002\/stem.190","article-title":"Depot-specific differences in adipogenic progenitor abundance and proliferative response to high-fat diet","volume":"27","author":"Joe","year":"2009","journal-title":"Stem Cells"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1017\/S0007114515001579","article-title":"Postnatal nutritional restriction affects growth and immune function of piglets with intra-uterine growth restriction","volume":"114","author":"Hu","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.ejphar.2015.03.044","article-title":"Considerations on pig models for appetite, metabolic syndrome and obese type 2 diabetes: From food intake to metabolic disease","volume":"759","author":"Koopmans","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"M17","DOI":"10.1530\/JOE-14-0217","article-title":"Early-postnatal changes in adiposity and lipids profile by transgenerational developmental programming in swine with obesity\/leptin resistance","volume":"223","author":"Astiz","year":"2014","journal-title":"J. Endocrinol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/age.12545","article-title":"A genome-wide association analysis for carcass traits in a commercial Duroc pig population","volume":"48","author":"Eusebi","year":"2017","journal-title":"Anim. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Barbero, A., Astiz, S., Lopez-Bote, C.J., Perez-Solana, M.L., Ayuso, M., Garcia-Real, I., and Gonzalez-Bulnes, A. (2013). Maternal Malnutrition and Offspring Sex Determine Juvenile Obesity and Metabolic Disorders in a Swine Model of Leptin Resistance. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078424"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/1128\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:48:41Z","timestamp":1760104121000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/1128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,17]]},"references-count":60,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25021128"],"URL":"https:\/\/doi.org\/10.3390\/ijms25021128","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,17]]}}}