{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:13:48Z","timestamp":1790183628786,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T00:00:00Z","timestamp":1543363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P011683\/1"],"award-info":[{"award-number":["MR\/P011683\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/G01812X\/1"],"award-info":[{"award-number":["BB\/G01812X\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Obesity is a growing health crisis of pandemic proportions. Numerous animal and human studies have confirmed that obesity and related metabolic abnormalities, such as insulin resistance and cardiovascular disease, may be programmed during development by adverse maternal nutrition. We previously documented that offspring of female mice who were protein-restricted during pregnancy alone had no alterations to their body weights, but did display a considerable reduction in food intake, a finding which was linked to reduced expression levels of appetite regulatory genes in the hypothalamus. Whether such observations were accompanied by changes in metabolic and phenotypic parameters remained to be determined. Female pregnant MF-1 mice were fed, exclusively during the pregnancy period, a normal protein diet containing 18% casein (C) or an isocaloric protein-restricted diet containing 9% casein (PR). From birth, the lactating dams were fed a normal protein diet. At weaning, offspring were fed either the standard chow which contain 7% kcal fat (C) or high-fat diet (HF, 45% kcal fat). This yielded 4 experimental groups denoted by maternal diet\/offspring diet: C\/C, C\/HF, PR\/C, PR\/HF. Our results showed that offspring adiposity was significantly increased in HF-fed offspring, and was not affected by the 50% reduction in protein content of the maternal diet fed during pregnancy. Similarly, blood glucose levels were higher in HF-fed offspring, regardless of protein content of the maternal diet. Systolic blood pressure, on the other hand, was significantly increased in both male and female offspring of dams fed the PR diet, and this was exacerbated by a postweaning HF diet. Our results show that maternal protein restriction leads to elevations in systolic blood pressure, which is exacerbated by a postweaning HF-diet. Our present findings suggest that, while changes in offspring adiposity brought about by exposure to maternal protein restriction during pregnancy may be restored by adequate maternal protein content during lactation, the same may not be true for systolic blood pressure, which was similarly impaired, regardless of the timing of maternal low-protein exposure.<\/jats:p>","DOI":"10.3390\/nu10121832","type":"journal-article","created":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T11:43:44Z","timestamp":1543405424000},"page":"1832","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Divergent Effect of Maternal Protein Restriction during Pregnancy and Postweaning High-Fat Diet Feeding on Blood Pressure and Adiposity in Adult Mouse Offspring"],"prefix":"10.3390","volume":"10","author":[{"given":"Dyan","family":"Sellayah","sequence":"first","affiliation":[{"name":"Harborne Building 12A, School of Biological Sciences, University of Reading, Whiteknights, Reading, Berkshire RG6 6AS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4404-9853","authenticated-orcid":false,"given":"Felino R.","family":"Cagampang","sequence":"additional","affiliation":[{"name":"Institute of Developmental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital (MP887), Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/sj.ijo.0802896","article-title":"Impact of morbid obesity on medical expenditures in adults","volume":"29","author":"Arterburn","year":"2005","journal-title":"Int. J. Obes. (Lond.)"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/S0140-6736(86)91340-1","article-title":"Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales","volume":"1","author":"Barker","year":"1986","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1159\/000115355","article-title":"Developmental origins of obesity and the metabolic syndrome: The role of maternal obesity","volume":"36","author":"Armitage","year":"2008","journal-title":"Front. Horm. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fnut.2018.00001","article-title":"Maternal high-fat and high-salt diets have differential programming effects on metabolism in adult male rat offspring","volume":"5","author":"Segovia","year":"2018","journal-title":"Front. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1002\/hep.23205","article-title":"Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression","volume":"50","author":"Bruce","year":"2009","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1093\/jn\/134.9.2169","article-title":"Maternal nutrition and fetal development","volume":"134","author":"Wu","year":"2004","journal-title":"J. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1113\/jphysiol.2004.078543","article-title":"A maternal low protein diet during pregnancy and lactation in the rat impairs male reproductive development","volume":"563","author":"Zambrano","year":"2005","journal-title":"J. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Garcia, A.P., Palou, M., S\u00e1nchez, J., Priego, T., Palou, A., and Pic\u00f3, C. (2011). Moderate caloric restriction during gestation in rats alters adipose tissue sympathetic innervation and later adiposity in offspring. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017313"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1017\/S0007114514000865","article-title":"Maternal protein restriction impairs the transcriptional metabolic flexibility of skeletal muscle in adult rat offspring","volume":"112","year":"2014","journal-title":"Br. J. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/1440-1681.12545","article-title":"Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring","volume":"43","author":"Qasem","year":"2016","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/ar.21084","article-title":"Effect of maternal protein restriction during pregnancy and lactation on the number of cardiomyocytes in the postproliferative weanling rat heart","volume":"293","author":"Lim","year":"2010","journal-title":"Anat. Rec. (Hoboken)"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1093\/jn\/124.9.1588","article-title":"The acute phase response of adult rats is altered by in utero exposure to maternal low protein diets","volume":"124","author":"Langley","year":"1994","journal-title":"J. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Watkins, A.J., Lucas, E.S., Wilkins, A., Cagampang, F.R., and Fleming, T.P. (2011). Maternal periconceptional and gestational low protein diet affects mouse offspring growth, cardiovascular and adipose phenotype at 1 year of age. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028745"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1079\/BJN20031029","article-title":"Prenatal programming of angiotensin II type 2 receptor expression in the rat","volume":"91","author":"McMullen","year":"2004","journal-title":"Br. J. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"E1702","DOI":"10.1152\/ajpendo.00605.2006","article-title":"Prenatal exposure to a low-protein diet programs disordered regulation of lipid metabolism in the aging rat","volume":"292","author":"Erhuma","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1203\/01.PDR.0000065731.00639.02","article-title":"Dietary protein restriction in pregnancy induces hypertension and vascular defects in rat male offspring","volume":"54","author":"Brawley","year":"2003","journal-title":"Pediatr. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1007\/s00394-014-0657-4","article-title":"Effect of maternal protein restriction during pregnancy and postweaning high-fat feeding on diet-induced thermogenesis in adult mouse offspring","volume":"53","author":"Sellayah","year":"2014","journal-title":"Eur J. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.tree.2005.08.001","article-title":"Predictive adaptive responses and human evolution","volume":"20","author":"Gluckman","year":"2005","journal-title":"Trends Ecol. Evol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E83","DOI":"10.1152\/ajpendo.2000.279.1.E83","article-title":"Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition","volume":"279","author":"Vickers","year":"2000","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"R2306","DOI":"10.1152\/ajpregu.00783.2006","article-title":"Programmed metabolic syndrome: Prenatal undernutrition and postweaning overnutrition","volume":"293","author":"Desai","year":"2007","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.brainres.2008.07.126","article-title":"Appetite regulatory mechanisms and food intake in mice are sensitive to mismatch in diets between pregnancy and postnatal periods","volume":"1237","author":"Sellayah","year":"2008","journal-title":"Brain Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1113\/jphysiol.2007.149229","article-title":"Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring","volume":"586","author":"Watkins","year":"2008","journal-title":"J. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1017\/S0029665199000804","article-title":"The long-term consequences of intra-uterine protein malnutrition for glucose metabolism","volume":"58","author":"Ozanne","year":"1999","journal-title":"Proc. Nutr. Soc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1017\/S0007114507812037","article-title":"A maternal \u2018junk food\u2019 diet in pregnancy and lactation promotes an exacerbated taste for \u2018junk food\u2019 and a greater propensity for obesity in rat offspring","volume":"98","author":"Bayol","year":"2007","journal-title":"Br. J. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"34345","DOI":"10.1038\/srep34345","article-title":"Maternal high-fat diet during lactation impairs thermogenic function of brown adipose tissue in offspring mice","volume":"6","author":"Liang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Knight, Z.A., Hannan, K.S., Greenberg, M.L., and Friedman, J.M. (2010). Hyperleptinemia is required for the development of leptin resistance. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011376"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"978","DOI":"10.2337\/diabetes.55.04.06.db05-1339","article-title":"Gonadal hormones determine sensitivity to central leptin and insulin","volume":"55","author":"Clegg","year":"2006","journal-title":"Diabetes"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/S0192-0561(99)00055-7","article-title":"Evidence for sexual dimorphism of estrogen receptors in hypothalamus and thymus of neonatal and immature Wistar rats","volume":"21","author":"Greenstein","year":"1999","journal-title":"Int J. Immunopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1017\/S0007114508988760","article-title":"Maternal undernutrition leads to endothelial dysfunction in adult male rat offspring independent of postnatal diet","volume":"101","author":"Torrens","year":"2009","journal-title":"Br. J. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1042\/cs0860217","article-title":"Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diets","volume":"86","author":"Langley","year":"1994","journal-title":"Clin. Sci. (Lond.)"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"R85","DOI":"10.1152\/ajpregu.00435.2004","article-title":"Maternal low-protein diet in rat pregnancy programs blood pressure through sex-specific mechanisms","volume":"288","author":"McMullen","year":"2005","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/S0024-3205(96)00611-X","article-title":"Intrauterine programming of hypertension by glucocorticoids","volume":"60","year":"1997","journal-title":"Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1113\/jphysiol.2002.026120","article-title":"Maternal protein restriction in the rat impairs resistance artery but not conduit artery function in pregnant offspring","volume":"547","author":"Torrens","year":"2003","journal-title":"J. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1038\/nm.3324","article-title":"Tracking adipogenesis during white adipose tissue development, expansion and regeneration","volume":"19","author":"Wang","year":"2013","journal-title":"Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1017\/S0029665112000584","article-title":"Adipose tissue development during early life: Novel insights into energy balance from small and large mammals","volume":"71","author":"Symonds","year":"2012","journal-title":"Proc. Nutr. Soc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"631038","DOI":"10.1155\/2012\/631038","article-title":"Developmental programming in response to intrauterine growth restriction impairs myoblast function and skeletal muscle metabolism","volume":"2012","author":"Yates","year":"2012","journal-title":"J. Pregnancy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.3390\/nu7021202","article-title":"Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity","volume":"7","author":"Dunlop","year":"2015","journal-title":"Nutrients"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/12\/1832\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:32:48Z","timestamp":1760196768000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/12\/1832"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,28]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["nu10121832"],"URL":"https:\/\/doi.org\/10.3390\/nu10121832","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,28]]}}}