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Children exposed to SSRIs in utero have an increased risk of being overweight suggesting that fetal exposure to SSRIs can cause permanent metabolic changes. We have previously shown in rats that fetal and neonatal exposure to the SSRI antidepressant fluoxetine results in metabolic perturbations including increased hepatic triglyceride content; a hallmark of non\u2010alcoholic fatty liver disease (NAFLD). Therefore, the aim of this study was to identify the mechanism(s) underlying the fluoxetine\u2010induced increase in intrahepatic triglyceride content. Female nulliparous Wistar rats were given vehicle or fluoxetine (10\u00a0mg\/kg\/day) orally for 2\u00a0weeks prior to mating until weaning. At 6\u00a0months of age, we assessed whether SSRI exposure altered components of the hepatic triglyceride biosynthesis pathway in the offspring and examined the molecular mechanisms underlying these changes. Male SSRI\u2010exposed offspring had a significant increase in the steady\u2010state mRNA levels of <jats:italic>Elovl6<\/jats:italic> and <jats:italic>Dgat1<\/jats:italic> and core components of the NLRP3 inflammasome (apoptosis\u2010associated speck\u2010like protein containing a caspase activation recruitment domain [ASC] and caspase\u20101). Augmented expression of <jats:italic>Asc<\/jats:italic> in the SSRI\u2010exposed offspring coincided with increased histone acetylation in the proximal promoter region. Given that we have previously demonstrated that antenatal exposure to SSRIs can lead to fatty liver in the offspring, this raises concerns regarding the long\u2010term metabolic sequelae of fetal SSRI exposure. Moreover, this study suggests that elevated hepatic triglyceride levels observed in the SSRI\u2010exposed offspring may be due, in part, to activation of the NLRP3 inflammasome and augmentation of de novo lipogenesis.<\/jats:p>","DOI":"10.1002\/jat.3502","type":"journal-article","created":{"date-parts":[[2017,7,5]],"date-time":"2017-07-05T06:32:37Z","timestamp":1499236357000},"page":"1507-1516","source":"Crossref","is-referenced-by-count":11,"title":["Increased incidence of non\u2010alcoholic fatty liver disease in male rat offspring exposed to fluoxetine during fetal and neonatal life involves the NLRP3 inflammasome and augmented de novo hepatic lipogenesis"],"prefix":"10.1002","volume":"37","author":[{"given":"Nicole E.","family":"De Long","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology McMaster University  Hamilton Ontario Canada L8S 4K1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5445-273X","authenticated-orcid":false,"given":"Daniel B.","family":"Hardy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Physiology and Pharmacology University of Western Ontario  London Ontario N6A 3K6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelle","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Physiology and Pharmacology University of Western Ontario  London Ontario N6A 3K6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4343-5325","authenticated-orcid":false,"given":"Alison C.","family":"Holloway","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology McMaster University  Hamilton Ontario Canada L8S 4K1"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,7,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.07.155"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2007.07.036"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00737-016-0637-1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13299"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2016.01.017"},{"key":"e_1_2_7_7_1","first-page":"9","article-title":"Epidemiology of depression throughout the female life cycle","volume":"63","author":"Burt V. 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