Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

Abstract : Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CURT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CURT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a ``two-programming'' hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is ``the first programming'', and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as ``the second programming''. (C) 2013 Elsevier Inc. All rights reserved.
Type de document :
Article dans une revue
Toxicology and Applied Pharmacology, Elsevier, 2014, 274 (2), pp.263-273. 〈10.1016/j.taap.2013.11.009〉
Liste complète des métadonnées

https://hal.univ-lorraine.fr/hal-01453214
Contributeur : Imopa Ul <>
Soumis le : jeudi 2 février 2017 - 16:12:53
Dernière modification le : jeudi 11 janvier 2018 - 06:25:37

Identifiants

Collections

Citation

Lang Shen, Zhongfen Liu, Jun Gong, Li Zhang, Linlong Wang, et al.. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats. Toxicology and Applied Pharmacology, Elsevier, 2014, 274 (2), pp.263-273. 〈10.1016/j.taap.2013.11.009〉. 〈hal-01453214〉

Partager

Métriques

Consultations de la notice

41