{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:35:39Z","timestamp":1790742939075,"version":"4.1.0"},"reference-count":81,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,11,13]],"date-time":"2014-11-13T00:00:00Z","timestamp":1415836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DP21DP2OD001500\u201001"],"award-info":[{"award-number":["DP21DP2OD001500\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:p>\n                    Intrauterine growth restriction (IUGR) confers heritable alterations in DNA methylation, rendering risk of adult metabolic syndrome (MetS). Because CpG methylation is coupled to intake of essential nutrients along the one\u2010carbon pathway, we reasoned that essential nutrient supplementation (ENS) may abrogate IUGR\u2010conferred multigenerational MetS. Pregnant Sprague\u2010Dawley rats underwent bilateral uterine artery ligation causing IUGR in F1. Among the F2 generation, IUGR lineage rats were underweight at birth (6.7\n                    <jats:italic>vs.<\/jats:italic>\n                    8.0 g,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001) and obese by adulthood (p160: 613\n                    <jats:italic>vs.<\/jats:italic>\n                    510 g;\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). Dual energy X\u2010ray absorptiometry studies revealed increased central fat mass (\u0394+40 g), accompanied by dyslipidemic (&gt;30% elevated,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05) serum triglycerides (139 mg\/dl), very\u2010LDLs (27.8 mg\/dl), and fatty acids (632 \u03bcM). Hyperglycemic\u2010euglycemic clamp studies and glucose tolerance testing revealed insulin resistance. Conversely, IUGR lineage ENS\u2010fed rats did not manifest MetS, with significantly lower body weight (p160: 410 g), &gt;5\u2010fold less central fat mass, normal hepatic glucose efflux, and &gt;70% reduced circulating triglycerides and very\u2010LDLs compared with IUGR control\u2010fed F2 offspring (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.01). Moreover, increased methylation of the IGF\u20101 P2 transcriptional start site among IUGR lineage F2 offspring was reversed in ENS (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.04). This is an initial demonstration that supplementation along the one\u2010carbon pathway abrogates adult morbidity and associated epigenomic modifications of IGF\u20101 in a rodent model of multigenerational MetS.\u2014Goodspeed, D., Seferovic, M. D., Holland, W., Mcknight, R. A., Summers, S. A., Branch, D. W., Lane, R. H., Aagaard, K. M., Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth\u2010restricted rats. FASEB J. 29, 807\u2013819 (2015).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.14-259614","type":"journal-article","created":{"date-parts":[[2014,11,14]],"date-time":"2014-11-14T01:49:49Z","timestamp":1415929789000},"page":"807-819","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth\u2010restricted rats"],"prefix":"10.1096","volume":"29","author":[{"given":"Danielle","family":"Goodspeed","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Baylor College of Medicine Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim D.","family":"Seferovic","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Baylor College of Medicine Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Holland","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Utah Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Mcknight","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Utah Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Summers","sequence":"additional","affiliation":[{"name":"Program in Cardiovascular and Metabolic Diseases Duke\u2010National University of Singapore Graduate Medical School Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Ware","family":"Branch","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Utah Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Lane","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Medical College of Wisconsin and Children's Hospital of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjersti M.","family":"Aagaard","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Baylor College of Medicine Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)90710-1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.298.6673.564"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66419-7"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2007.00531.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00399095"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.307.6918.1524"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.6.1310"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.12.3246"},{"key":"e_1_2_7_10_1","first-page":"1","article-title":"Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003\u20102006","volume":"13","author":"Ervin R. B.","year":"2009","journal-title":"National Health Statistics Report"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-9-48"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2008-0024"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61794-3"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.10.2279"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-006-0196-5"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0490"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.219147"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0395"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.5.7.12882"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.6.2.13472"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2009.02.019"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-172080"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.303.6809.1019"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806560105"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2008.01822.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(86)90064-8"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198501000-00010"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00211.2005"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1999.276.1.E135"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200107000-00016"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.143.7.2486"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00093.2005"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00880.2005"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-124768"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32011"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00052.2010"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199610313351805"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0452"},{"key":"e_1_2_7_39_1","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1210\/jcem.85.4.6495","article-title":"Effects of insulin\u2010like growth factor I (IGF\u2010I) therapy on body composition and insulin resistance in IGF\u2010I gene deletion","volume":"85","author":"Woods K. A.","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2012.09.007"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi114"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.15.5293-5300.2003"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2003.09.011"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi484"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/1358863X08100834"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1805"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.22.010402.102932"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.112.048462"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.08.022"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/132.8.2333S"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2012.03.003"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665111003338"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3889"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12263-012-0300-z"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.07.004"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.280.1.R183"},{"issue":"2","key":"e_1_2_7_57_1","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1093\/jn\/123.suppl_2.438","article-title":"Soft tissue composition and bone mineral status: evaluation by dual\u2010energy X\u2010ray absorptiometry","volume":"123","author":"Lukaski H. C.","year":"1993","journal-title":"J. Nutr."},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.163477"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-448-3_15"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.01.002"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.2.411"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh103"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-12-0560"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2008.12.015"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00042.2004"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00175.2004"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2004.04.015"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.095133"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/ilar.53.3-4.306"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0657"},{"key":"e_1_2_7_71_1","doi-asserted-by":"crossref","first-page":"5325","DOI":"10.1021\/pr900633x","article-title":"Site specific phosphorylation of insulin\u2010like growth factor binding protein\u20101 (IGFBP\u20101) for evaluating clinical relevancy in fetal growth restriction","volume":"8","author":"Abu Shehab M.","year":"2009","journal-title":"J. Proteome Res."},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0606"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.7.1539"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.10.2483"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00462.2006"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.109.119453"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-6179fje"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000064583.40495.51"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2010.30064"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-8227com"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3435"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-8229com"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.14-259614","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.14-259614","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.14-259614","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T01:00:49Z","timestamp":1761699649000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.14-259614"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,13]]},"references-count":81,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1096\/fj.14-259614"],"URL":"https:\/\/doi.org\/10.1096\/fj.14-259614","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,13]]},"assertion":[{"value":"2014-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-10-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-11-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}