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Recently, we reported that prenatal nicotine exposure (PNE) induced an abnormal level of total cholesterol in rat offspring before and after birth. However, there were little data about sex differences in serum cholesterol level in PNE offspring. In addition, many previous studies reported that blood cholesterol is associated with daily diet. This study was designed to analyse the interaction among PNE, high\u2010fat diet (HFD) and sex on cholesterol metabolism in the rat. Pregnant Wistar rats were administered 2\u00a0mg\/kg nicotine subcutaneously from gestational day (GD) 11 until parturition. After weaning, pups were fed with normal diet or HFD till 24\u00a0weeks, and then, serum cholesterol phenotypes and hepatic cholesterol metabolism\u2010related genes were tested. Results showed that PNE manifested a distinct programming effect on cholesterol phenotype and cholesterol metabolism\u2010related genes. HFD aggregated PNE\u2010induced hypercholesterolaemia in adult offspring and exacerbated liver cholesterol metabolism dysfunction in PNE offspring. There was no sex difference in serum cholesterol level, but there were interactions among PNE, HFD and sex on cholesterol metabolic genes in adult offspring, which indicates that cholesterol metabolism in female offspring is more likely to be affected by PNE and HFD. In conclusion, HFD exacerbated PNE\u2010induced hypercholesterolaemia, and sex differences existed in liver cholesterol metabolic genes in PNE\u2010 or HFD\u2010treated offspring.<\/jats:p>","DOI":"10.1111\/bcpt.13187","type":"journal-article","created":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T12:36:15Z","timestamp":1544790975000},"page":"730-740","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synergistic effects of prenatal nicotine exposure and post\u2010weaning high\u2010fat diet on hypercholesterolaemia in rat offspring of different sexes"],"prefix":"10.1111","volume":"124","author":[{"given":"Chunyan","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Science Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of 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