{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:05:33Z","timestamp":1790485533531,"version":"4.1.0"},"reference-count":41,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2016,11,23]],"date-time":"2016-11-23T00:00:00Z","timestamp":1479859200000},"content-version":"vor","delay-in-days":1453,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/us\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human and animal studies suggest that suboptimal early nutrition during critical developmental periods impacts long-term health. For example, maternal overnutrition during pregnancy and lactation in mice programs insulin resistance, obesity, and endothelial dysfunction in the offspring. Here we investigated the effects of diet-induced maternal obesity on the offspring cardiac phenotype and explored potential underlying molecular mechanisms. Dams fed the obesogenic diet were heavier (P &amp;lt; 0.01) and fatter (P &amp;lt; 0.0001) than controls throughout pregnancy and lactation. There was no effect of maternal obesity on offspring body weight or body composition up to 8 wk of age. However, maternal obesity resulted in increased offspring cardiac mass (P &amp;lt; 0.05), increased heart-body weight (P &amp;lt; 0.01), heart weight-tibia length (P &amp;lt; 0.05), increased left ventricular free wall thickness and area (P &amp;lt; 0.01 and P &amp;lt; 0.05, respectively), and increased myocyte width (P &amp;lt; 0.001). Consistent with these structural changes, the expression of molecular markers of cardiac hypertrophy were also increased [Nppb(BNP), Myh7-Myh6(\u03b2MHC-\u03b1MHC) (both P &amp;lt; 0.05) and mir-133a (P &amp;lt; 0.01)]. Offspring were hyperinsulinemic and displayed increased insulin action through AKT (P &amp;lt; 0.01), ERK (P &amp;lt; 0.05), and mammalian target of rapamycin (P &amp;lt; 0.05). p38MAPK phosphorylation was also increased (P &amp;lt; 0.05), suggesting pathological remodeling. Increased Ncf2(p67phox) expression (P &amp;lt; 0.05) and impaired manganese superoxide dismutase levels (P &amp;lt; 0.01) suggested oxidative stress, which was consistent with an increase in levels of 4-hydroxy-2-trans-nonenal (a measure of lipid peroxidation). We propose that maternal diet-induced obesity leads to offspring cardiac hypertrophy, which is independent of offspring obesity but is associated with hyperinsulinemia-induced activation of AKT, mammalian target of rapamycin, ERK, and oxidative stress.<\/jats:p>","DOI":"10.1210\/en.2012-1508","type":"journal-article","created":{"date-parts":[[2012,10,16]],"date-time":"2012-10-16T06:03:17Z","timestamp":1350367397000},"page":"5961-5971","source":"Crossref","is-referenced-by-count":129,"title":["The Programming of Cardiac Hypertrophy in the Offspring by Maternal Obesity Is Associated with Hyperinsulinemia, AKT, ERK, and mTOR Activation"],"prefix":"10.1210","volume":"153","author":[{"given":"Denise S.","family":"Fernandez-Twinn","sequence":"first","affiliation":[{"name":"Metabolic Research Laboratories (D.S.F.-T., H.L.B., S.E.O.), University of Cambridge, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather L.","family":"Blackmore","sequence":"first","affiliation":[{"name":"Metabolic Research Laboratories (D.S.F.-T., H.L.B., S.E.O.), University of Cambridge, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Siggens","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine (L.S., R.F.), Addenbrooke's Centre for Clinical Investigation, University of Cambridge, Cambridge CB2 0QQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dino A.","family":"Giussani","sequence":"first","affiliation":[{"name":"Department of Physiology Development and Neuroscience (D.A.G., C.M.C.), University of Cambridge, Cambridge CB2 3EG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Cross","sequence":"first","affiliation":[{"name":"Department of Physiology Development and Neuroscience (D.A.G., C.M.C.), University of Cambridge, Cambridge CB2 3EG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Foo","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine (L.S., R.F.), Addenbrooke's Centre for Clinical Investigation, University of Cambridge, Cambridge CB2 0QQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Ozanne","sequence":"first","affiliation":[{"name":"Metabolic Research Laboratories (D.S.F.-T., H.L.B., S.E.O.), University of Cambridge, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613043762900_B1","doi-asserted-by":"crossref","first-page":"588S","DOI":"10.1080\/07315724.2004.10719428","article-title":"The developmental origins of adult disease.","volume":"23","author":"Barker","year":"2004","journal-title":"J Am Coll Nutr"},{"key":"2020071613043762900_B2","doi-asserted-by":"crossref","first-page":"1344S","DOI":"10.1093\/ajcn\/71.5.1344s","article-title":"Fetal nutrition and adult disease.","volume":"71","author":"Godfrey","year":"2000","journal-title":"Am J Clin Nutr"},{"key":"2020071613043762900_B3","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1375\/twin.4.5.293","article-title":"Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview.","volume":"4","author":"Roseboom","year":"2001","journal-title":"Twin 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activation of superoxide-producing NADPH oxidases.","volume":"278","author":"Takeya","year":"2003","journal-title":"J Biol Chem"},{"key":"2020071613043762900_B38","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1006\/abbi.2001.2601","article-title":"Role of p38 mitogen-activated protein kinase in the 4-hydroxy-2-nonenal-induced cyclooxygenase-2 expression.","volume":"397","author":"Kumagai","year":"2002","journal-title":"Arch Biochem Biophys"},{"key":"2020071613043762900_B39","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1016\/j.febslet.2007.04.048","article-title":"The lipid peroxidation end-product 4-HNE induces COX-2 expression through p38MAPK activation in 3T3-L1 adipose cell.","volume":"581","author":"Zarrouki","year":"2007","journal-title":"FEBS Lett"},{"key":"2020071613043762900_B40","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1083\/jcb.142.2.523","article-title":"Stimulation of the p38 mitogen-activated protein kinase pathway in neonatal rat 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