title: Increased susceptibility of prenatal food restricted offspring to high-fat diet-induced nonalcoholic fatty liver disease is intrauterine programmed.
abstract: The present study aims to explore the mechanisms of fetal origin of high susceptibility to adult high-fat diet induced-nonalcoholic fatty liver disease in rat offspring undergoing intrauterine growth retardation (IUGR) induced by prenatal food restriction (FR) from gestational day 11 until full-term delivery. We observed that adult IUGR offspring rats exhibited gender-dependent catch-up growth with lower serum corticosterone (CORT) but up-regulation of the insulin-like growth factor 1 (IGF1) pathway, higher hepatic Kleiner scores and lower lipid export and oxidation. Furthermore, fetal IUGR offspring rats showed lower body weights with higher serum CORT but down-regulated IGF1 pathway, which was accompanied by enhanced lipid de novo synthetic gene expression, lower lipid output and oxidation gene expression. It is suggested that a "two-programming" mechanism, which refers to the adverse intrauterine programming of hepatic lipid de novo synthesis and glucocorticoid-IGF1 axis programming associated with postnatal catch-up growth, could explain the increased susceptibility.
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
authors.forename: Linlong
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
authors.forename: Zhongfen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
authors.forename: Yansong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Liu
authors.affiliation: UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Magdalou
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
authors.forename: Liaobin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China. Electronic address: wanghui19@whu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D059305:Diet, High-Fat; D005260:Female; D047109:Fetal Development; D048070:Fetal Nutrition Disorders; D018507:Gene Expression Regulation, Developmental; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000235:genetics; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology* / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D017451:Receptors, Somatomedin / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D051273:Glucose Transporter Type 2; D055504:Insulin Receptor Substrate Proteins; C526299:Irs2 protein, rat; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; C495683:Slc2a2 protein, rat; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; C548904:insulin-like growth factor-1, rat; C106092:microsomal triglyceride transfer protein; D007334:Insulin-Like Growth Factor I; D005947:Glucose
keywords: Fetal origin; Glucocorticoid-insulin-like growth factor 1 axis; Glucose and lipid metabolism; Nonalcoholic fatty liver disease (NAFLD); “Two-programming” mechanism