Glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis programming mediated hepatic lipid-metabolic in offspring caused by prenatal ethanol exposure. (1st October 2020)

• Record Type: Journal Article
• Authors: Hu, Wen; Yuan, Chao; Luo, Hanwen; Hu, Shuwei; Shen, Lang; Chen, Liaobin; Xu, Dan; Wang, Hui
• Is Part Of: Toxicology letters. Volume 331(2020)
• Page Start: 167
• Page End: 177
• Publication Date: 2020-10-01
• Subjects: 11β-HSD1 11β-hydroxysteroid dehydrogenase type 1 -- 11β-HSD2 11β-hydroxysteroid dehydrogenase type 2 -- AKT2 protein kinase B β -- C/EBPα CCAAT/enhancer-binding protein α -- FASN fatty acid synthase -- GC-IGF1 glucocorticoid-insulin-like growth factor 1 -- GD gestational day -- GR glucocorticoid receptor -- GH growth hormone -- GREs glucocorticoid response elements -- 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 -- PEE prenatal ethanol exposure -- PW postnatal week -- TCH total cholesterol; Prenatal ethanol exposure -- Intrauterine programming -- Glucocorticoid-insulin-like growth factor 1 axis -- Lipid metabolism -- Histone modification; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2020.06.008
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: PEE induced a long-time liver dysfunction. Glucocorticoid-activation system participated in liver development. Glucocorticoids epigenetically regulated expression of IGF1. Abstract: Prenatal ethanol exposure (PEE) could increase offspring's susceptibility to adult liver lipid-metabolism diseases. This study aimed to confirm intrauterine programming mechanism of glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis for liver dysfunction in offspring rats induced by PEE. The results showed that levels of hepatic IGF1, lipid metabolism-related enzymes ( e.g. FASN and HMGCR) and serum phenotype (TG, TCH, HDL-C, and LDL-C) were low in fetal rats of PEE but high in adult offspring except for HDL-C, meanwhile, hepatic H3K9ac and expression levels of IGF1 were low in fetal rats but high in adult offspring. Furthermore, levels of serum corticosterone and hepatic glucocorticoid-activation system (mainly including expression of 11β-HSD1, GR, and C/EBPα as well as 11β-HSD1/11β-HSD2 ratio) were high in fetal rats of PEE but low or unchanged in adult offspring. The adult F2 generation of PEE maintained the same GC-IGF1 axis programming alteration as the F1 generation despite gender differences. In vitro, cortisol was proved to activate hepatocyte glucocorticoid-activation system and decrease H3K9ac and expression levels of IGF1 by GR. Therefore, PEE has a long-term effect on the offspring's liver functional development, which may be mainly related to the epigenetic programming alteration of the GC-IGF1 axis mediated by the glucocorticoid-activation system.