{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T20:41:44Z","timestamp":1774039304225,"version":"3.50.1"},"reference-count":38,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,12,1]]},"abstract":"<jats:p>Despite medical advice, 20\u201330% of female smokers continue to smoke during pregnancy. Epidemiological studies have associated maternal smoking with increased risk of obesity and type-2 diabetes in the offspring. In the present study, we investigated the impact of prenatal nicotine exposure (3 mg\/kg in Sprague Dawley rats via osmotic Alzet minipumps) on the early endocrine pancreas and adipose tissue development in rat pups before weaning. Body weight, fat deposition, food intake and food efficiency, cold tolerance, spontaneous physical activity, glucose utilization, and insulin sensitivity were also examined at adulthood. Prenatal nicotine exposure led to a decrease in endocrine pancreatic islet size and number at 7 d of life (postnatal d 7), which corroborates with a decrease in gene expression of specific transcription factors such as pancreatic and duodenal homeobox 1, Pax-6, Nkx6.1, and of hormones such as insulin and glucagon. The prenatal nicotine exposure also led to an increase in epididymal white adipose tissue weight at weaning (postnatal d 21), and marked hypertrophy of adipocytes, with increased gene expression of proadipogenic transcription factors such as CAAT-enhancer-binding protein-\u03b1, peroxisome proliferator activated receptor-\u03b3, and sterol regulatory element binding protein-1C. These early tissue alterations led to significant metabolic consequences, as shown by increased body weight and fat deposition, increased food efficiency on high-fat diet, cold intolerance, reduced physical activity, and glucose intolerance combined with insulin resistance observed at adulthood. These results prove a direct association between fetal nicotine exposure and offspring metabolic syndrome with early signs of dysregulations of adipose tissue and pancreatic development.<\/jats:p>","DOI":"10.1210\/en.2008-0361","type":"journal-article","created":{"date-parts":[[2008,8,8]],"date-time":"2008-08-08T00:46:12Z","timestamp":1218156372000},"page":"6289-6299","source":"Crossref","is-referenced-by-count":132,"title":["Prenatal Nicotine Exposure Alters Early Pancreatic Islet and Adipose Tissue Development with Consequences on the Control of Body Weight and Glucose Metabolism Later in Life"],"prefix":"10.1210","volume":"149","author":[{"given":"Emmanuel","family":"Somm","sequence":"first","affiliation":[{"name":"Department of Pediatrics (E.S., V.M.S., D.M.V., E.J.C., S.V.S., M.L.A., P.S.H.), Geneva University Hospitals, 1211 Geneva 14, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vale\u0301rie M.","family":"Schwitzgebel","sequence":"first","affiliation":[{"name":"Department of Pediatrics (E.S., V.M.S., D.M.V., E.J.C., S.V.S., M.L.A., P.S.H.), Geneva University Hospitals, 1211 Geneva 14, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delphine M.","family":"Vauthay","sequence":"first","affiliation":[{"name":"Department of Pediatrics (E.S., V.M.S., D.M.V., E.J.C., S.V.S., M.L.A., P.S.H.), Geneva University Hospitals, 1211 Geneva 14, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily J.","family":"Camm","sequence":"first","affiliation":[{"name":"Department of Pediatrics (E.S., V.M.S., D.M.V., E.J.C., S.V.S., M.L.A., P.S.H.), Geneva University Hospitals, 1211 Geneva 14, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang Y.","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology (C.Y.C.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Paul","family":"Giacobino","sequence":"first","affiliation":[{"name":"Department of Cell Physiology and Metabolism (J.-P.G.), University Medical Center, 1211 Geneva 4, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ste\u0301phane V.","family":"Sizonenko","sequence":"first","affiliation":[{"name":"Department of Pediatrics (E.S., V.M.S., D.M.V., E.J.C., S.V.S., M.L.A., P.S.H.), Geneva University Hospitals, 1211 Geneva 14, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel L.","family":"Aubert","sequence":"first","affiliation":[{"name":"Department of Pediatrics (E.S., V.M.S., D.M.V., E.J.C., S.V.S., M.L.A., P.S.H.), Geneva University Hospitals, 1211 Geneva 14, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra S.","family":"Hu\u0308ppi","sequence":"first","affiliation":[{"name":"Department of Pediatrics (E.S., V.M.S., D.M.V., E.J.C., S.V.S., M.L.A., P.S.H.), Geneva University Hospitals, 1211 Geneva 14, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2008,8,7]]},"reference":[{"key":"2020071612142244200_R1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.tem.2004.03.002","article-title":"The developmental origins of the metabolic syndrome.","volume":"15","author":"Gluckman","year":"2004","journal-title":"Trends Endocrinol Metab"},{"key":"2020071612142244200_R2","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/BF00400248","article-title":"Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis.","volume":"35","author":"Hales","year":"1992","journal-title":"Diabetologia"},{"key":"2020071612142244200_R3","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":"2020071612142244200_R4","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1053\/plac.1998.0377","article-title":"Cigarette smoking and pregnancy I: ovarian, uterine and placental effects.","volume":"20","author":"Shiverick","year":"1999","journal-title":"Placenta"},{"key":"2020071612142244200_R5","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0301-2115(00)00421-8","article-title":"Origins of fetal growth restriction.","volume":"92","author":"Robinson","year":"2000","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2020071612142244200_R6","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1079\/BJN19840004","article-title":"Maternal adipose tissue response to nicotine administration in the pregnant rat: effects on fetal body fat and cellularity.","volume":"51","author":"Williams","year":"1984","journal-title":"Br J Nutr"},{"key":"2020071612142244200_R7","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1093\/ije\/31.2.413","article-title":"Fetal environment and subsequent obesity: a study of maternal smoking.","volume":"31","author":"Power","year":"2002","journal-title":"Int J Epidemiol"},{"key":"2020071612142244200_R8","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1038\/oby.2005.248","article-title":"Associations of maternal prenatal smoking with child adiposity and blood pressure.","volume":"13","author":"Oken","year":"2005","journal-title":"Obes Res"},{"key":"2020071612142244200_R9","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/oby.2005.77","article-title":"Prenatal exposure to nicotine causes postnatal obesity and altered perivascular adipose tissue function.","volume":"13","author":"Gao","year":"2005","journal-title":"Obes Res"},{"key":"2020071612142244200_R10","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1007\/s00125-005-0022-5","article-title":"Fetal and neonatal exposure to nicotine in Wistar rats results in increased \u03b2 cell apoptosis at birth and postnatal endocrine and metabolic changes associated with type 2 diabetes.","volume":"48","author":"Holloway","year":"2005","journal-title":"Diabetologia"},{"key":"2020071612142244200_R11","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1677\/JOE-07-0050","article-title":"Fetal and neonatal nicotine exposure and postnatal glucose homeostasis: identifying critical windows of exposure.","volume":"194","author":"Bruin","year":"2007","journal-title":"J Endocrinol"},{"key":"2020071612142244200_R12","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1002\/bdra.20162","article-title":"Fetal nicotinic overload, blunted sympathetic responsivity, and obesity.","volume":"73","author":"Levin","year":"2005","journal-title":"Birth Defects Res A Clin Mol Teratol"},{"key":"2020071612142244200_R13","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.cmet.2007.08.015","article-title":"Foxa2 controls vesicle docking and insulin secretion in mature \u03b2 cells.","volume":"6","author":"Gao","year":"2007","journal-title":"Cell Metab"},{"key":"2020071612142244200_R14","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1136\/bmj.324.7328.26","article-title":"Smoking during pregnancy and diabetes mellitus in a British longitudinal birth cohort.","volume":"324","author":"Montgomery","year":"2002","journal-title":"BMJ"},{"key":"2020071612142244200_R15","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1006\/enrs.2002.4395","article-title":"Variation of serum and urine cotinine in passive and active smokers and applicability in preconceptional smoking cessation counseling.","volume":"90","author":"Weerd","year":"2002","journal-title":"Environ Res"},{"key":"2020071612142244200_R16","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1056\/NEJM199911253412216","article-title":"Use of the nicotine patch by pregnant women.","volume":"341","author":"Hackman","year":"1999","journal-title":"N Engl J Med"},{"key":"2020071612142244200_R17","first-page":"P4","volume-title":"Program of the 89th Annual Meeting of The Endocrine Society,","author":"Bruin","year":"2007"},{"key":"2020071612142244200_R18","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1016\/j.freeradbiomed.2008.02.010","article-title":"Maternal nicotine exposure increases oxidative stress in the offspring.","volume":"44","author":"Bruin","year":"2008","journal-title":"Free Radic Biol Med"},{"key":"2020071612142244200_R19","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1093\/toxsci\/kfn012","article-title":"Increased pancreatic \u03b2 cell apoptosis following fetal and neonatal exposure to nicotine is mediated via the mitochondria.","volume":"103","author":"Bruin","year":"2008","journal-title":"Toxicol Sci"},{"key":"2020071612142244200_R20","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1007\/s10024-003-2014-0","article-title":"Developmentally regulated expression of Survivin in human pancreatic islets.","volume":"6","author":"Liggins","year":"2003","journal-title":"Pediatr Dev Pathol"},{"key":"2020071612142244200_R21","doi-asserted-by":"crossref","first-page":"6332","DOI":"10.1073\/pnas.0509313103","article-title":"Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating XIAP and survivin.","volume":"103","author":"Dasgupta","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612142244200_R22","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.ijom.2007.05.016","article-title":"Nicotine inhibits apoptosis induced by cisplatin in human oral cancer cells.","volume":"36","author":"Xu","year":"2007","journal-title":"Int J Oral Maxillofac Surg"},{"key":"2020071612142244200_R23","doi-asserted-by":"crossref","first-page":"102","DOI":"10.2337\/diabetes.52.1.102","article-title":"\u03b2-Cell deficit and increased \u03b2-cell apoptosis in humans with type 2 diabetes.","volume":"52","author":"Butler","year":"2003","journal-title":"Diabetes"},{"key":"2020071612142244200_R24","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.lfs.2007.07.017","article-title":"Quantification of PPAR-\u03b3 protein in monocyte\/macrophages from healthy smokers and non-smokers: a possible direct effect of nicotine.","volume":"81","author":"Amoruso","year":"2007","journal-title":"Life Sci"},{"key":"2020071612142244200_R25","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1385\/MN:22:1-3:143","article-title":"Regulation of feeding-associated peptides and receptors by nicotine.","volume":"22","author":"Li","year":"2000","journal-title":"Mol Neurobiol"},{"key":"2020071612142244200_R26","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1515\/JPM.2003.034","article-title":"Maternal smoking during pregnancy and appetite control in offspring.","volume":"31","author":"Toschke","year":"2003","journal-title":"J Perinat Med"},{"key":"2020071612142244200_R27","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.pbb.2006.10.012","article-title":"Effects of maternal intravenous nicotine administration on locomotor behavior in pre-weanling rats.","volume":"85","author":"LeSage","year":"2006","journal-title":"Pharmacol Biochem Behav"},{"key":"2020071612142244200_R28","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.pbb.2006.11.020","article-title":"Long-term behavioral and developmental consequences of pre- and perinatal nicotine.","volume":"85","author":"Eppolito","year":"2006","journal-title":"Pharmacol Biochem Behav"},{"key":"2020071612142244200_R29","doi-asserted-by":"crossref","first-page":"D883","DOI":"10.2741\/A472","article-title":"The effect of nicotine on developing brain catecholamine systems","volume":"4","author":"Oliff","year":"1999","journal-title":"Front Biosci"},{"key":"2020071612142244200_R30","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/nature05414","article-title":"An obesity-associated gut microbiome with increased capacity for energy harvest.","volume":"444","author":"Turnbaugh","year":"2006","journal-title":"Nature"},{"key":"2020071612142244200_R31","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.chom.2008.02.015","article-title":"Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome.","volume":"3","author":"Turnbaugh","year":"2008","journal-title":"Cell Host Microbe"},{"key":"2020071612142244200_R32","first-page":"110","article-title":"The biochemistry of an inefficient tissue: brown adipose tissue.","volume":"20","author":"Cannon","year":"1985","journal-title":"Essays Biochem"},{"key":"2020071612142244200_R33","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0361-9230(90)90066-9","article-title":"Prenatal nicotine exposure impairs \u03b2-adrenergic function: persistent chronotropic subsensitivity despite recovery from deficits in receptor binding.","volume":"25","author":"Navarro","year":"1990","journal-title":"Brain Res Bull"},{"key":"2020071612142244200_R34","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0014-5793(02)03387-2","article-title":"\u03b2(1)\/\u03b2(2)\/\u03b2(3)-adrenoceptor knockout mice are obese and cold-sensitive but have normal lipolytic responses to fasting.","volume":"530","author":"Jimenez","year":"2002","journal-title":"FEBS Lett"},{"key":"2020071612142244200_R35","doi-asserted-by":"crossref","first-page":"3490","DOI":"10.2337\/diabetes.54.12.3490","article-title":"The lack of \u03b2-adrenoceptors results in enhanced insulin sensitivity in mice exhibiting increased adiposity and glucose intolerance.","volume":"54","author":"Asensio","year":"2005","journal-title":"Diabetes"},{"key":"2020071612142244200_R36","doi-asserted-by":"crossref","first-page":"728","DOI":"10.2337\/diacare.16.5.728","article-title":"Effects of age and body fat on insulin resistance in healthy men.","volume":"16","author":"Boden","year":"1993","journal-title":"Diabetes Care"},{"key":"2020071612142244200_R37","doi-asserted-by":"crossref","first-page":"633","DOI":"10.2337\/diab.45.5.633","article-title":"Abdominal fat and insulin resistance in normal and overweight women: direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM.","volume":"45","author":"Carey","year":"1996","journal-title":"Diabetes"},{"key":"2020071612142244200_R38","first-page":"1306","article-title":"Evaluation of abdominal fat distribution in noninsulin-dependent diabetes mellitus: relationship to insulin resistance.","volume":"83","author":"Gautier","year":"1998","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/149\/12\/6289\/8999837\/endo6289.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/149\/12\/6289\/8999837\/endo6289.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T19:37:10Z","timestamp":1594928230000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/149\/12\/6289\/2455448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8,7]]},"references-count":38,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2008,12,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2008-0361","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,8,7]]}}}