PMID- 22583948
OWN - NLM
STAT- MEDLINE
DCOM- 20121009
LR  - 20140128
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 262
IP  - 2
DP  - 2012 Jul 15
TI  - Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to 
      the increased circulatory glucocorticoid level and altered peripheral glucose and 
      lipid metabolic pathways.
PG  - 205-16
LID - 10.1016/j.taap.2012.05.002 [doi]
AB  - The aims of this study were to clarify the metabonome alteration in fetal rats 
      after prenatal caffeine ingestion and to explore the underlying mechanism 
      pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant 
      Wistar rats were daily intragastrically administered with different doses of 
      caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. 
      Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by (1)H nuclear 
      magnetic resonance-based metabonomics. Gene and protein expressions involved in 
      the GC metabolism, glucose and lipid metabolic pathways in fetal liver and 
      gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal 
      plasma metabonome were significantly altered by caffeine, which presents as the 
      elevated alpha- and beta-glucose, reduced multiple lipid contents, varied apolipoprotein 
      contents and increased levels of a number of amino acids. The metabonome of 
      amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the 
      expressions of 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD-2) were decreased, 
      while the level of blood GC and the expressions of 11beta-HSD-1 and glucocorticoid 
      receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the 
      expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin 
      receptor were decreased, while the expressions of adiponectin receptor 2, leptin 
      receptors and AMP-activated protein kinase alpha2 were increased after caffeine 
      treatment. Prenatal caffeine ingestion characteristically change the fetal 
      metabonome, which is probably attributed to the alterations of glucose and lipid 
      metabolic pathways induced by increased circulatory GC, activated GC metabolism 
      and enhanced GR expression in peripheral metabolic tissues.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Liu, Yansong
AU  - Liu Y
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 
      University, Wuhan 430071, China.
FAU - Xu, Dan
AU  - Xu D
FAU - Feng, Jianghua
AU  - Feng J
FAU - Kou, Hao
AU  - Kou H
FAU - Liang, Gai
AU  - Liang G
FAU - Yu, Hong
AU  - Yu H
FAU - He, Xiaohua
AU  - He X
FAU - Zhang, Baifang
AU  - Zhang B
FAU - Chen, Liaobin
AU  - Chen L
FAU - Magdalou, Jacques
AU  - Magdalou J
FAU - Wang, Hui
AU  - Wang H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120511
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 3G6A5W338E (Caffeine)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
EIN - Toxicol Appl Pharmacol. 2013 Dec 15;273(3):691
MH  - Animals
MH  - Caffeine/*toxicity
MH  - Central Nervous System Stimulants/*toxicity
MH  - Female
MH  - Fetus
MH  - Glucocorticoids/genetics/metabolism
MH  - Glucose/*metabolism
MH  - Lipid Metabolism/*drug effects
MH  - Liver/drug effects/embryology/metabolism
MH  - Magnetic Resonance Spectroscopy
MH  - Male
MH  - Metabolomics/methods
MH  - Muscle, Skeletal/drug effects/embryology/metabolism
MH  - *Paternal Exposure
MH  - Pregnancy
MH  - Principal Component Analysis
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Glucocorticoid/genetics/metabolism
MH  - Specific Pathogen-Free Organisms
EDAT- 2012/05/16 06:00
MHDA- 2012/10/10 06:00
CRDT- 2012/05/16 06:00
PHST- 2012/02/02 00:00 [received]
PHST- 2012/04/11 00:00 [revised]
PHST- 2012/05/02 00:00 [accepted]
PHST- 2012/05/16 06:00 [entrez]
PHST- 2012/05/16 06:00 [pubmed]
PHST- 2012/10/10 06:00 [medline]
AID - S0041-008X(12)00200-1 [pii]
AID - 10.1016/j.taap.2012.05.002 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2012 Jul 15;262(2):205-16. doi: 
      10.1016/j.taap.2012.05.002. Epub 2012 May 11.