{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T14:27:11Z","timestamp":1782484031132,"version":"3.54.5"},"reference-count":71,"publisher":"Cambridge University Press (CUP)","issue":"5","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"unspecified","delay-in-days":61,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["J Dev Orig Health Dis"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nonalcoholic fatty liver disease (NAFLD) involves changes in hepatic pathways, as lipogenesis, oxidative stress, endoplasmic reticulum (ER) stress, and macroautophagy. Maternal nicotine exposure exclusively during lactation leads to fatty liver (steatosis) only in the adult male offspring, not in females. Therefore, our hypothesis is that neonatal exposure to nicotine sex-dependently affects the signaling pathways involved in hepatic homeostasis of the offspring, explaining the hepatic lipid accumulation phenotype only in males. For this, between postnatal days 2 and 16, Wistar rat dams were implanted with osmotic minipumps, which released nicotine (NIC; 6 mg\/Kg\/day) or vehicle. The livers of offspring were evaluated at postnatal day 180. Only the male offspring that had been exposed to nicotine neonatally showed increased protein expression of markers of unfolded protein response (UPR), highlighting the presence of ER stress, as well as disruption of the activation of the macroautophagy repair pathway. These animals also had increased expression of diacylglycerol O-acyltransferase 1 and 4-hydroxynonenal, suggesting increased triglyceride esterification and oxidative stress. These parameters were not altered in the female offspring that had been neonatally exposed to nicotine, however they exhibited increased phospho adenosine monophosphate-activated protein kinase pAMPK expression, possibly as a protective mechanism. Thus, the disturbance in the hepatic homeostasis by UPR, macroautophagy, and oxidative stress modifications seem to be the molecular mechanisms underlying the liver steatosis in the adult male offspring of the nicotine-programming model. This highlights the importance of maternal smoking cessation during breastfeeding to decrease the risk of NAFLD development, especially in males.<\/jats:p>","DOI":"10.1017\/s2040174423000326","type":"journal-article","created":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T10:12:24Z","timestamp":1701425544000},"page":"639-647","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":3,"title":["Neonatal nicotine exposure affects adult rat hepatic pathways involved in endoplasmic reticulum stress and macroautophagy in a sex-dependent manner"],"prefix":"10.1017","volume":"14","author":[{"given":"Luana Lopes","family":"Souza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila L\u00fcdke","family":"Rossetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamara Cherem","family":"Peixoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4629-8343","authenticated-orcid":false,"given":"Alex Christian","family":"Manh\u00e3es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1159-7549","authenticated-orcid":false,"given":"Egberto Gaspar","family":"de Moura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2477-4364","authenticated-orcid":false,"given":"Patr\u00edcia Cristina","family":"Lisboa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2023,12,1]]},"reference":[{"key":"S2040174423000326_ref24","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijheatmasstransfer.2015.02.040"},{"key":"S2040174423000326_ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.01.026"},{"key":"S2040174423000326_ref54","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1100356"},{"key":"S2040174423000326_ref2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30626"},{"key":"S2040174423000326_ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2019.113781"},{"key":"S2040174423000326_ref35","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2013.168"},{"key":"S2040174423000326_ref69","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-10-0104"},{"key":"S2040174423000326_ref13","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201600171"},{"key":"S2040174423000326_ref71","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2018.09.007"},{"key":"S2040174423000326_ref48","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2014.06.007"},{"key":"S2040174423000326_ref25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-72725-w"},{"key":"S2040174423000326_ref30","doi-asserted-by":"publisher","DOI":"10.1113\/EP087518"},{"key":"S2040174423000326_ref5","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2860-6"},{"key":"S2040174423000326_ref66","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1750"},{"key":"S2040174423000326_ref20","article-title":"National, regional, and global prevalence of smoking during pregnancy in the general population: a systematic review and meta-analysis","volume":"6","author":"Lange","year":"2018","journal-title":"Lancet Glob Heal"},{"key":"S2040174423000326_ref3","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kws448"},{"key":"S2040174423000326_ref50","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1728097"},{"key":"S2040174423000326_ref61","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00225.2016"},{"key":"S2040174423000326_ref62","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.12.036"},{"key":"S2040174423000326_ref60","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2014.02.002"},{"key":"S2040174423000326_ref68","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1839"},{"key":"S2040174423000326_ref19","doi-asserted-by":"publisher","DOI":"10.1542\/peds.108.3.776"},{"key":"S2040174423000326_ref7","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-015-4025-x"},{"key":"S2040174423000326_ref39","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.1.3"},{"key":"S2040174423000326_ref46","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2006"},{"key":"S2040174423000326_ref58","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201900838"},{"key":"S2040174423000326_ref16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0207818"},{"key":"S2040174423000326_ref36","doi-asserted-by":"publisher","DOI":"10.1590\/S0102-86502009000100015"},{"key":"S2040174423000326_ref63","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17020192"},{"key":"S2040174423000326_ref42","first-page":"55","article-title":"Immunoblotting (Western blot). in: basic molecular protocols in neuroscience: tips, tricks, and pitfalls","author":"Corthell","year":"2014","journal-title":"Elsevier"},{"key":"S2040174423000326_ref49","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-020-00414-0"},{"key":"S2040174423000326_ref64","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-72022-6"},{"key":"S2040174423000326_ref11","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202100514"},{"key":"S2040174423000326_ref12","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12138"},{"key":"S2040174423000326_ref45","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.04.011"},{"key":"S2040174423000326_ref67","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0122295"},{"key":"S2040174423000326_ref43","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2012.02.017"},{"key":"S2040174423000326_ref9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-020117-043617"},{"key":"S2040174423000326_ref27","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1055\/s-0031-1285909","article-title":"Developmental plasticity in adrenal function and leptin production primed by nicotine exposure during lactation: gender differences in rats","volume":"43","author":"Pinheiro","year":"2011","journal-title":"Horm Metab Res"},{"key":"S2040174423000326_ref1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28431"},{"key":"S2040174423000326_ref56","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2022.148098"},{"key":"S2040174423000326_ref14","doi-asserted-by":"publisher","DOI":"10.3390\/ijms141122052"},{"key":"S2040174423000326_ref40","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-09-0430"},{"key":"S2040174423000326_ref59","doi-asserted-by":"publisher","DOI":"10.1080\/09637486.2016.1261086"},{"key":"S2040174423000326_ref70","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2020.111328"},{"key":"S2040174423000326_ref37","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.1473"},{"key":"S2040174423000326_ref4","first-page":"1495","article-title":"A simple clinical model predicts incident hepatic steatosis in a community-based cohort: the framingham heart study","volume":"38","author":"Long","year":"2018","journal-title":"Liver Int Off J Int Assoc Study Liver"},{"key":"S2040174423000326_ref38","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(85)80427-3"},{"key":"S2040174423000326_ref21","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2022.101660"},{"key":"S2040174423000326_ref41","first-page":"1","article-title":"Nicotine exposure during breastfeeding alters the expression of endocannabinoid system biomarkers in female but not in male offspring at adulthood","volume":"14","author":"Miranda","year":"2023","journal-title":"J Dev Orig Health Dis. Published online February"},{"key":"S2040174423000326_ref55","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(08)03601-X"},{"key":"S2040174423000326_ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.06.008"},{"key":"S2040174423000326_ref8","doi-asserted-by":"publisher","DOI":"10.1111\/eci.13622"},{"key":"S2040174423000326_ref10","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00029.2013"},{"key":"S2040174423000326_ref31","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201900838"},{"key":"S2040174423000326_ref32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00295.2016"},{"key":"S2040174423000326_ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2004.12.057"},{"key":"S2040174423000326_ref47","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-014-3167-6"},{"key":"S2040174423000326_ref51","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2018.08.001"},{"key":"S2040174423000326_ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2015.01.025"},{"key":"S2040174423000326_ref53","doi-asserted-by":"publisher","DOI":"10.1038\/nature07976"},{"key":"S2040174423000326_ref18","doi-asserted-by":"publisher","DOI":"10.1016\/S0749-3797(02)00574-3"},{"key":"S2040174423000326_ref22","doi-asserted-by":"publisher","DOI":"10.1100\/2012\/154910"},{"key":"S2040174423000326_ref34","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-022-00562-w"},{"key":"S2040174423000326_ref44","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-1252-6"},{"key":"S2040174423000326_ref26","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-09-0020"},{"key":"S2040174423000326_ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2007.09.002"},{"key":"S2040174423000326_ref57","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-016-0476-6"},{"key":"S2040174423000326_ref65","article-title":"Cigarette smoke during breastfeeding in rats changes glucocorticoid and vitamin D status in obese adult offspring","volume":"19","author":"Soares","year":"2018","journal-title":"Int J Mol Sci"},{"key":"S2040174423000326_ref15","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29347"},{"key":"S2040174423000326_ref52","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1055\/s-0039-1681032","article-title":"Endoplasmic reticulum stress in metabolic liver diseases and hepatic fibrosis","volume":"39","author":"Maiers","year":"2019","journal-title":"Semin Liver Dis"}],"container-title":["Journal of Developmental Origins of Health and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S2040174423000326","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T05:32:38Z","timestamp":1704951158000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S2040174423000326\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10]]},"references-count":71,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["S2040174423000326"],"URL":"https:\/\/doi.org\/10.1017\/s2040174423000326","relation":{},"ISSN":["2040-1744","2040-1752"],"issn-type":[{"value":"2040-1744","type":"print"},{"value":"2040-1752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10]]},"assertion":[{"value":"\u00a9 The Author(s), 2023. Published by Cambridge University Press in association with The International Society for Developmental Origins of Health and Disease (DOHaD)","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}}]}}