PMID- 30776459
OWN - NLM
STAT- MEDLINE
DCOM- 20200114
LR  - 20200114
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 417
DP  - 2019 Apr 1
TI  - Prenatal caffeine exposure increases the susceptibility to non-alcoholic fatty 
      liver disease in female offspring rats via activation of GR-C/EBPalpha-SIRT1 pathway.
PG  - 23-34
LID - S0300-483X(18)30318-4 [pii]
LID - 10.1016/j.tox.2019.02.008 [doi]
AB  - This study aimed to evaluate female adult offspring induced by prenatal caffeine 
      exposure (PCE) are susceptible to non-alcoholic fatty liver disease (NAFLD) and 
      to explore the underlying programming mechanisms. Pregnant rats were 
      intragastrically administered caffeine (30, 60, and 120 mg/kg.d) on gestational 
      day (GD) 9-20. The female adult offspring were randomly divided into three 
      groups: offspring without or with chronic stress during postnatal week (PW) 10-12 
      and PW28 offspring. Results showed that PW28 PCE female offspring had a higher 
      hepatic triglyceride content and Kleiner scores, accompanied by elevated serum 
      corticosterone levels. Moreover, the expression levels of hepatic glucocorticoid 
      receptor (GR), CCAAT enhancer binding protein alpha (C/EBPalpha), fatty acid synthetase 
      (FASN) and the transcription factor-sterol regulatory element binding protein 1c 
      (SREBP1c) were increased, but SIRT1 expression was decreased. The fetal rats and 
      PW12 offspring with chronic stress exhibited similar changes as PW28 offspring, 
      accompanied by increased levels of H3K14ac and H3K27ac in the SREBP1c and FASN 
      gene promoters. These effects were also observed by treating L02 cells with 
      cortisol and were partially reversed by GR or C/EBPalpha siRNA or treatment with the 
      SIRT1 agonist resveratrol. Taken together, PCE-induced high glucocorticoids 
      levels enhanced histone modifications and expression of SREBP1c and FASN via 
      activation of the GR-C/EBPalpha-SIRT1 pathway in utero. This enhanced female fetal 
      hepatic triglyceride synthesis and continued throughout postnatal and adult life, 
      increasing the susceptibility to adult NAFLD.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Hu, Shuwei
AU  - Hu S
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 
      430071, China.
FAU - Xia, Liping
AU  - Xia L
AD  - Department of Pediatrics, Renmin Hospital of Wuhan University, Hubei General 
      Hospital, Wuhan, 430060, China; Hubei Provincial Key Laboratory of 
      Developmentally Originated Disease, Wuhan, 430071, China.
FAU - Luo, Hanwen
AU  - Luo H
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 
      430071, China.
FAU - Xu, Yanyong
AU  - Xu Y
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      430071, China.
FAU - Yu, Hong
AU  - Yu H
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      430071, China.
FAU - Xu, Dan
AU  - Xu D
AD  - 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: xuyidan70188@whu.edu.cn.
FAU - Wang, Hui
AU  - Wang H
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190215
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (CCAAT-Binding Factor)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 3G6A5W338E (Caffeine)
RN  - EC 3.5.1.- (Sirt1 protein, rat)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Animals
MH  - CCAAT-Binding Factor/*metabolism
MH  - Caffeine/administration & dosage/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Non-alcoholic Fatty Liver Disease/chemically induced/*metabolism/pathology
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/chemically induced/*metabolism/pathology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Glucocorticoid/*metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Sirtuin 1/*metabolism
OTO - NOTNLM
OT  - Caffeine
OT  - Hepatic triglyceride metabolism
OT  - Histone acetylation
OT  - Intrauterine programming mechanism
EDAT- 2019/02/19 06:00
MHDA- 2020/01/15 06:00
CRDT- 2019/02/19 06:00
PHST- 2018/08/31 00:00 [received]
PHST- 2019/01/31 00:00 [revised]
PHST- 2019/02/13 00:00 [accepted]
PHST- 2019/02/19 06:00 [pubmed]
PHST- 2020/01/15 06:00 [medline]
PHST- 2019/02/19 06:00 [entrez]
AID - S0300-483X(18)30318-4 [pii]
AID - 10.1016/j.tox.2019.02.008 [doi]
PST - ppublish
SO  - Toxicology. 2019 Apr 1;417:23-34. doi: 10.1016/j.tox.2019.02.008. Epub 2019 Feb 
      15.