Effects of prenatal nicotine exposure on hepatic glucose and lipid metabolism in offspring rats and its hereditability. (28th February 2020)

• Record Type: Journal Article
• Authors: Hu, Wen; Wang, Guihua; He, Bo; Hu, Shuwei; Luo, Hanwen; Wen, Yinxian; Chen, Liaobin; Wang, Hui
• Is Part Of: Toxicology. Volume 432(2020)
• Publication Date: 2020-02-28
• Subjects: Akt2 Protein kinase B b -- Cebpa CCAAT/enhancer-binding protein a -- Fasn fatty acid synthase -- G6p glucose 6-phosphate -- GC-IGF1 glucocorticoid-insulin-like growth factor 1 -- GD gestational day -- Hsd11b1 11β-hydroxysteroid dehydrogenase type 1 -- Hsd11b2 11β-hydroxysteroid dehydrogenase type 2 -- Hmgcr 3-hydroxy-3-methylglutaryl-CoA reductase -- HPA hypothalamic-pituitary-adrenal -- HDL-C high-density lipoprotein-cholesterol -- Igf1 insulin-like growth factor 1 -- Igf1r insulin-like growth factor 1 receptor -- IUGR intrauterine growth retardation -- LDL-C low-density lipoprotein cholesterol -- MS metabolic syndrome -- Nr3c1 nuclear receptor subfamily 3, group C, member 1 -- PNE prenatal nicotine exposure -- PW postnatal week -- TCH total cholesterol -- TG Triglyceride; Prenatal nicotine exposure -- Glucocorticoid -- Intrauterine programming of glucocorticoid-insulin-like growth factor 1 axis -- Glucose and lipid metabolism -- Epigenetic modification; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2020.152378
• Languages: English
• ISSNs: 0300-483X

Abstract

Highlights: PNE produces a long-lasting impact on liver glucose and lipid metabolic function. PNE induced glucose and lipid metabolic changes by GC-IGF1 axis. The glucocorticoid -activation system mediated liver glucose and lipid metabolic. Abstract: Prenatal nicotine exposure (PNE) could induce an increased susceptibility to multiple chronic diseases in adult offspring, that mainly caused by intrauterine maternal glucocorticoid (GC) over-exposure. We investigated the changes and inheritability of hepatic glucose and lipid metabolism caused by PNE, to decipher the possible intrauterine programming mechanism. Pregnant Wistar rats were administered subcutaneously with 2 mg/kg·d nicotine from gestational day (GD) 9∼20, and second-generation (F2) were set according to the mating between control females and PNE males. The results showed that serum phenotypes and hepatic enzymes of glucose and lipid metabolism were lower in F1 fetal rats of PNE but higher in the F1 adult rats. Meanwhile, the activated states of hepatic glucocorticoid-activation system, including type 1 and type 2 11β-hydroxysteroid dehydrogenases ( Hsd11b1/2 ), nuclear receptor subfamily 3, group C, member 1 ( Nr3c1 ) and CCAAT enhancer binding protein α ( Cebpa ), were positively correlated with serum corticosterone levels but negatively correlated with the histone acetylation (H3K27ac) and expression levels of insulin-like growth factor 1 ( Igf1 ) before and after birth. Furthermore, serum phenotypes and hepatic enzymes of glucose and lipid metabolism were lower in both F2 fetal and adult rats of PNE, which were consistent with the hepatic changes of GC-IGF1 axis and the glucocorticoid-activation system. In conclusion, PNE could lead to inheritable changes of hepatic glucose and lipid metabolism, which are related to the intrauterine programming of GC-IGF1 axis induced by the glucocorticoid-activation system.