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Gestational exposure to the air pollutant ozone is associated with fetal growth restriction in humans and rodents. However, the impact of this early life ozone exposure on offspring metabolic risk has not yet been investigated. In this study, fetal growth restriction was induced by maternal inhalation of 0.8\u00a0ppm ozone on gestation days 5 and 6 (4\u00a0hr\/day) in Long Evans rats. To uncover any metabolic inflexibility, or an impaired ability to respond to a high\u2010fat diet (HFD), a subset of peri\u2010adolescent male and female offspring from filtered air or ozone exposed dams were fed HFD (45% kcal from fat) for 3\u2009days. By 6\u2009weeks of age, male and female offspring from ozone\u2010exposed dams were heavier than offspring from air controls. Furthermore, offspring from ozone\u2010exposed dams had greater daily caloric consumption and reduced metabolic rate when fed HFD. In addition to energy imbalance, HFD\u2010fed male offspring from ozone\u2010exposed dams had dyslipidemia and increased adiposity, which was not evident in females. HFD consumption in males resulted in the activation of the protective 5'AMP\u2010activated protein kinase (AMPK\u03b1) and sirtuin 1 (SIRT1) pathways in the liver, regardless of maternal exposure. Unlike males, ozone\u2010exposed female offspring failed to activate these pathways, retaining hepatic triglycerides following HFD consumption that resulted in increased inflammatory gene expression and reduced insulin signaling genes. Taken together, maternal ozone exposure in early pregnancy programs impaired metabolic flexibility in offspring, which may increase susceptibility to obesity in males and hepatic dysfunction in females.<\/jats:p>","DOI":"10.1096\/fj.202201514r","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T07:07:03Z","timestamp":1669100823000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Prenatal ozone exposure programs a sexually dimorphic susceptibility to high\u2010fat diet in adolescent\n                    <scp>Long Evans<\/scp>\n                    rats"],"prefix":"10.1096","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5632-6120","authenticated-orcid":false,"given":"Erica J.","family":"Stewart","sequence":"first","affiliation":[{"name":"Oak Ridge Institute for Science and Education, Center for Public Health and Environmental Assessment U.S. Environmental 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