{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:07:53Z","timestamp":1792739273581,"version":"4.5.0"},"reference-count":82,"publisher":"Cambridge University Press (CUP)","issue":"2","license":[{"start":{"date-parts":[[2007,3,7]],"date-time":"2007-03-07T00:00:00Z","timestamp":1173225600000},"content-version":"unspecified","delay-in-days":675,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proc. Nutr. Soc."],"published-print":{"date-parts":[[2005,5]]},"abstract":"<jats:p>A number of epidemiological studies worldwide have demonstrated a relationship between poor early growth and an increased susceptibility to insulin resistance, visceral obesity, type 2 diabetes and other features of the metabolic syndrome in adulthood. However, the mechanistic basis of this relationship and the relative roles of genes and the environment remain a subject of debate. The \u2018thrifty phenotype\u2019 hypothesis proposes that poor fetal nutrition leads to programming of metabolism and an adult phenotype that is adapted to poor but not plentiful nutrition. The maternal reduced-protein rat model has been used to examine the importance of the maternal environment in determining susceptibility to adult disease. Pregnant and lactating rat dams are fed a diet containing 80 g protein\/kg as compared with 200 g protein\/kg, which leads to growth restriction <jats:italic>in utero<\/jats:italic>. Offspring of low-protein dams have increased susceptibility to diabetes, insulin resistance and hypertension when fed a palatable high-fat diet that promotes obesity. Administration of leptin during pregnancy and lactation to these protein-restricted dams produces offspring that have increased metabolic rate and do not become obese or insulin resistant when fed on a high-fat diet. Increased glucocorticoid exposure, particularly during late gestation, has been linked with insulin resistance in adulthood. High levels of fetal glucocorticoids may result from a decreased activity of placental 11\u03b2-hydroxysteroid dehydrogenase (11\u03b2-HSD) type 2, which normally protects the fetus from high maternal glucocorticoid levels. Leptin administration to protein-restricted dams inhibits the suppression of 11\u03b2-HSD-2 and may be one mechanism by which the metabolic syndrome is prevented.<\/jats:p>","DOI":"10.1079\/pns2005417","type":"journal-article","created":{"date-parts":[[2005,6,15]],"date-time":"2005-06-15T20:10:40Z","timestamp":1118866240000},"page":"143-151","source":"Crossref","is-referenced-by-count":137,"title":["Fetal origins of insulin resistance and obesity"],"prefix":"10.1017","volume":"64","author":[{"given":"Claire J.","family":"Stocker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R. S.","family":"Arch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Cawthorne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2007,3,7]]},"reference":[{"key":"S0029665105000182_ref046","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1760013"},{"key":"S0029665105000182_ref018","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/133.12.4196"},{"key":"S0029665105000182_ref063","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.35.6.1301"},{"key":"S0029665105000182_ref077","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1790293"},{"key":"S0029665105000182_ref042","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2003.63"},{"key":"S0029665105000182_ref062","doi-asserted-by":"publisher","DOI":"10.1042\/cs0930147"},{"key":"S0029665105000182_ref021","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/60.1.89"},{"key":"S0029665105000182_ref048","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1567"},{"key":"S0029665105000182_ref054","doi-asserted-by":"publisher","DOI":"10.1038\/427411b"},{"key":"S0029665105000182_ref051","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(75)92605-7"},{"key":"S0029665105000182_ref020","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/60.1.33"},{"key":"S0029665105000182_ref055","doi-asserted-by":"publisher","DOI":"10.1042\/CS20030278"},{"key":"S0029665105000182_ref035","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199715050-00010"},{"key":"S0029665105000182_ref061","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-5491.2000.00392.x"},{"key":"S0029665105000182_ref009","doi-asserted-by":"publisher","DOI":"10.1042\/bj3131007"},{"key":"S0029665105000182_ref072","doi-asserted-by":"publisher","DOI":"10.1159\/000243170"},{"key":"S0029665105000182_ref069","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2002.tb02874.x"},{"key":"S0029665105000182_ref005","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1997.1230939.x"},{"key":"S0029665105000182_ref075","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802476"},{"key":"S0029665105000182_ref050","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200212000-00009"},{"key":"S0029665105000182_ref030","doi-asserted-by":"publisher","DOI":"10.1515\/JPM.2001.003"},{"key":"S0029665105000182_ref029","doi-asserted-by":"publisher","DOI":"10.1038\/953"},{"key":"S0029665105000182_ref058","first-page":"E559","article-title":"Altered regulation of hepatic glucose output in the male offspring of protein-malnourished rat dams","volume":"270","author":"Ozanne","year":"1996","journal-title":"American Journal of Physiology"},{"key":"S0029665105000182_ref008","doi-asserted-by":"publisher","DOI":"10.1126\/science.1095004"},{"key":"S0029665105000182_ref002","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1176"},{"key":"S0029665105000182_ref047","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.11.2854"},{"key":"S0029665105000182_ref071","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0145"},{"key":"S0029665105000182_ref080","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.15.5293-5300.2003"},{"key":"S0029665105000182_ref023","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199710000-00016"},{"key":"S0029665105000182_ref038","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.003269"},{"key":"S0029665105000182_ref034","doi-asserted-by":"publisher","DOI":"10.1016\/0300-9629(94)90124-4"},{"key":"S0029665105000182_ref012","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.5.1090"},{"key":"S0029665105000182_ref073","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-030031"},{"key":"S0029665105000182_ref011","first-page":"4490","article-title":"Expression of type 2 11beta-hydroxysteroid dehydrogenase and corticosteroid hormone receptors in early human fetal life","volume":"83","author":"Condon","year":"1998","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"S0029665105000182_ref053","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665199000804"},{"key":"S0029665105000182_ref001","doi-asserted-by":"publisher","DOI":"10.1136\/adc.81.5.395"},{"key":"S0029665105000182_ref016","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1096\/fasebj.11.5.9141506","article-title":"Leptin gene is expressed in rat brown adipose tissue at birth","volume":"11","author":"Dessolin","year":"1997","journal-title":"FASEB Journal"},{"key":"S0029665105000182_ref068","doi-asserted-by":"publisher","DOI":"10.1385\/ENDO:19:1:65"},{"key":"S0029665105000182_ref043","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(02)00690-2"},{"key":"S0029665105000182_ref057","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1770235"},{"key":"S0029665105000182_ref056","first-page":"E46","article-title":"Poor fetal nutrition causes long-term changes in expression of insulin signaling components in adipocytes","volume":"273","author":"Ozanne","year":"1997","journal-title":"American Journal of Physiology"},{"key":"S0029665105000182_ref041","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2002.tb02871.x"},{"key":"S0029665105000182_ref006","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/129.8.1613"},{"key":"S0029665105000182_ref019","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.318.7181.427"},{"key":"S0029665105000182_ref045","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-5491.2003.00871.x"},{"key":"S0029665105000182_ref040","doi-asserted-by":"publisher","DOI":"10.1007\/s001250050573"},{"key":"S0029665105000182_ref024","doi-asserted-by":"publisher","DOI":"10.1071\/RD9951227"},{"key":"S0029665105000182_ref065","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.11.8512"},{"key":"S0029665105000182_ref039","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.5.8139"},{"key":"S0029665105000182_ref014","first-page":"G1083","article-title":"Programming of hepatic insulin-sensitive enzymes in offspring of rat dams fed a protein-restricted diet","volume":"272","author":"Desai","year":"1997","journal-title":"American Journal of Physiology"},{"key":"S0029665105000182_ref010","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1590341"},{"key":"S0029665105000182_ref070","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod66.6.1762"},{"key":"S0029665105000182_ref049","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.84.3.5657"},{"key":"S0029665105000182_ref027","doi-asserted-by":"publisher","DOI":"10.1042\/bst0240341"},{"key":"S0029665105000182_ref052","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/60.1.143"},{"key":"S0029665105000182_ref013","first-page":"2244","article-title":"Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess","volume":"83","author":"Dave-Sharma","year":"1998","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"S0029665105000182_ref026","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.303.6809.1019"},{"key":"S0029665105000182_ref004","doi-asserted-by":"publisher","DOI":"10.1007\/BF00399095"},{"key":"S0029665105000182_ref079","first-page":"E83","article-title":"Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition","volume":"279","author":"Vickers","year":"2000","journal-title":"American Journal of Physiology"},{"key":"S0029665105000182_ref025","doi-asserted-by":"publisher","DOI":"10.1007\/BF00400248"},{"key":"S0029665105000182_ref017","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/57.2.140"},{"key":"S0029665105000182_ref031","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1286.035"},{"key":"S0029665105000182_ref037","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.312.7028.401"},{"key":"S0029665105000182_ref082","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0756fje"},{"key":"S0029665105000182_ref036","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4004(96)80010-5"},{"key":"S0029665105000182_ref078","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-002-0983-z"},{"key":"S0029665105000182_ref022","first-page":"267","article-title":"Intrauterine programming of adult body composition","volume":"86","author":"Gale","year":"2001","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"S0029665105000182_ref064","doi-asserted-by":"publisher","DOI":"10.1007\/s001250050698"},{"key":"S0029665105000182_ref076","first-page":"641","article-title":"Maternal leptin administration induces resistance to diet-induced obesity of early growth restricted rats","volume":"44","author":"Stocker","year":"2001","journal-title":"Diabetologia"},{"key":"S0029665105000182_ref067","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)07244-9"},{"key":"S0029665105000182_ref059","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1093\/jn\/133.10.3085","article-title":"Fetal and early postnatal protein malnutrition cause long-term changes in rat liver and muscle mitochondria","volume":"133","author":"Park","year":"2003","journal-title":"Journal of Nutrition"},{"key":"S0029665105000182_ref066","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-220593"},{"key":"S0029665105000182_ref028","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.024406"},{"key":"S0029665105000182_ref033","first-page":"1401","article-title":"Insulin resistance early in adulthood in subjects born with intrauterine growth retardation","volume":"85","author":"Jaquet","year":"2000","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"S0029665105000182_ref044","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.324.7328.26"},{"key":"S0029665105000182_ref081","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1540177"},{"key":"S0029665105000182_ref074","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1208-3"},{"key":"S0029665105000182_ref007","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0320"},{"key":"S0029665105000182_ref003","doi-asserted-by":"publisher","DOI":"10.1038\/382250a0"},{"key":"S0029665105000182_ref032","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021332"},{"key":"S0029665105000182_ref015","doi-asserted-by":"publisher","DOI":"10.1079\/BJN19960065"},{"key":"S0029665105000182_ref060","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/61.3.528"}],"container-title":["Proceedings of the Nutrition Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0029665105000182","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,3]],"date-time":"2019-05-03T16:58:17Z","timestamp":1556902697000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0029665105000182\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,5]]},"references-count":82,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2005,5]]}},"alternative-id":["S0029665105000182"],"URL":"https:\/\/doi.org\/10.1079\/pns2005417","relation":{},"ISSN":["0029-6651","1475-2719"],"issn-type":[{"value":"0029-6651","type":"print"},{"value":"1475-2719","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,5]]}}}