{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T07:36:45Z","timestamp":1769845005161,"version":"3.49.0"},"reference-count":22,"publisher":"Cambridge University Press (CUP)","issue":"3","license":[{"start":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T00:00:00Z","timestamp":1172707200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Nutr"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:p>Epidemiological studies and experimental models show that maternal nutritional constraint during pregnancy alters the metabolic phenotype of the offspring and that this can be passed to subsequent generations. In the rat, induction of an altered metabolic phenotype in the liver of the F<jats:sub>1<\/jats:sub> generation by feeding a protein-restricted diet (PRD) during pregnancy involves the altered methylation of specific gene promoters. We therefore investigated whether the altered methylation of PPAR\u03b1 and glucocorticoid receptor (GR) promoters was passed to the F<jats:sub>2<\/jats:sub> generation. Females rats (F<jats:sub>0<\/jats:sub>) were fed a reference diet (180\u00a0g\/kg protein) or PRD (90\u00a0g\/kg protein) throughout gestation, and AIN-76A during lactation. The F<jats:sub>1<\/jats:sub> offspring were weaned onto AIN-76A. F<jats:sub>1<\/jats:sub> females were mated and fed AIN-76A throughout pregnancy and lactation. F<jats:sub>1<\/jats:sub> and F<jats:sub>2<\/jats:sub> males were killed on postnatal day 80. Hepatic PPAR\u03b1 and GR promoter methylation was significantly (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b705) lower in the PRD group in the F<jats:sub>1<\/jats:sub> (PPAR\u03b1 8\u00a0%, GR 10\u00a0%) and F<jats:sub>2<\/jats:sub> (PPAR\u03b1 11\u00a0%, GR 8\u00a0%) generations. There were trends (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b71) towards a higher expression of PPAR\u03b1, GR, acyl-CoA oxidase and phosphoenolpyruvate carboxykinase (PEPCK) in the F<jats:sub>1<\/jats:sub> and F<jats:sub>2<\/jats:sub> males, although this was significant only for PEPCK. These data show for the first time that the altered methylation of gene promoters induced in the F<jats:sub>1<\/jats:sub> generation by maternal protein restriction during pregnancy is transmitted to the F<jats:sub>2<\/jats:sub> generation. This may represent a mechanism for the transmission of induced phenotypes between generations.<\/jats:p>","DOI":"10.1017\/s0007114507352392","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T10:03:29Z","timestamp":1172052209000},"page":"435-439","source":"Crossref","is-referenced-by-count":356,"title":["Dietary protein restriction of pregnant rats in the F<sub>0<\/sub> generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F<sub>1<\/sub> and F<sub>2<\/sub> generations"],"prefix":"10.1017","volume":"97","author":[{"given":"Graham C.","family":"Burdge","sequence":"first","affiliation":[]},{"given":"Jo","family":"Slater-Jefferies","sequence":"additional","affiliation":[]},{"given":"Christopher","family":"Torrens","sequence":"additional","affiliation":[]},{"given":"Emma S.","family":"Phillips","sequence":"additional","affiliation":[]},{"given":"Mark A.","family":"Hanson","sequence":"additional","affiliation":[]},{"given":"Karen A.","family":"Lillycrop","sequence":"additional","affiliation":[]}],"member":"56","published-online":{"date-parts":[[2007,3,1]]},"reference":[{"key":"S0007114507352392_ref23","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.086462"},{"key":"S0007114507352392_ref20","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201538"},{"key":"S0007114507352392_ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2004.10.018"},{"key":"S0007114507352392_ref24","doi-asserted-by":"publisher","DOI":"10.1042\/cs0860217"},{"key":"S0007114507352392_ref13","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1639"},{"key":"S0007114507352392_ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2004.03.002"},{"key":"S0007114507352392_ref22","first-page":"41P","article-title":"First evidence for transgenerational vascular programming in the rat protein restriction model","volume":"543P","author":"Torrens","year":"2002","journal-title":"J Physiol"},{"key":"S0007114507352392_ref2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-006-0196-5"},{"key":"S0007114507352392_ref18","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-9084(00)01147-0"},{"key":"S0007114507352392_ref4","doi-asserted-by":"publisher","DOI":"10.1101\/gad.947102"},{"key":"S0007114507352392_ref7","first-page":"R34","article-title":"Intergenerational consequences of fetal programming by in utero exposure to glucocorticoids in rats","volume":"288","author":"Drake","year":"2005","journal-title":"Am J Physiol"},{"key":"S0007114507352392_ref14","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10168"},{"key":"S0007114507352392_ref15","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/135.6.1382"},{"key":"S0007114507352392_ref11","doi-asserted-by":"publisher","DOI":"10.1079\/PHN2001145"},{"key":"S0007114507352392_ref5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119703"},{"key":"S0007114507352392_ref16","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/130.4.741"},{"key":"S0007114507352392_ref3","doi-asserted-by":"publisher","DOI":"10.1530\/rep.0.1240459"},{"key":"S0007114507352392_ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2005.04.005"},{"key":"S0007114507352392_ref21","first-page":"641","article-title":"The relationship between maternal and offspring birth weights after maternal prenatal famine exposure: the Dutch Famine Birth Cohort Study","volume":"72","author":"Stein","year":"2000","journal-title":"Hum Biol"},{"key":"S0007114507352392_ref1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrc.20039"},{"key":"S0007114507352392_ref12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109609200"},{"key":"S0007114507352392_ref6","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0250169"}],"container-title":["British Journal of Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0007114507352392","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T16:53:13Z","timestamp":1554742393000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0007114507352392\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007,3]]}},"alternative-id":["S0007114507352392"],"URL":"https:\/\/doi.org\/10.1017\/s0007114507352392","relation":{},"ISSN":["0007-1145","1475-2662"],"issn-type":[{"value":"0007-1145","type":"print"},{"value":"1475-2662","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,3]]}}}