PMID- 30377736
OWN - NLM
STAT- MEDLINE
DCOM- 20200518
LR  - 20200518
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Linking)
VI  - 93
IP  - 2
DP  - 2019 Feb
TI  - Exposure of pregnant mice to triclosan causes hyperphagic obesity of offspring 
      via the hypermethylation of proopiomelanocortin promoter.
PG  - 547-558
LID - 10.1007/s00204-018-2338-1 [doi]
AB  - Triclosan (TCS), as a broad spectrum antibacterial agent, is commonly utilized in 
      personal care and household products. Maternal urinary TCS level has been 
      associated with changes in birth weight of infants. We in the present study 
      investigated whether exposure of mice to 8 mg/kg TCS from gestational day (GD) 6 
      to GD14 alters prenatal and postnatal growth and development, and metabolic 
      phenotypes in male and female offspring (TCS-offspring). Compared with control 
      offspring, body weight in postnatal day (PND) 1 male or female TCS-offspring was 
      reduced, but body weight gain was faster within postnatal 5 days. PND30 and PND60 
      TCS-offspring showed overweight with increases in visceral fat and adipocyte 
      size. PND60 TCS-offspring displayed delayed glucose clearance and insulin 
      resistance. PND30 TCS-offspring showed an increase in food intake without the 
      changes in the oxygen consumption and respiratory exchange ratio (RER). The 
      expression levels of proopiomelanocortin (POMC), alpha-melanocyte-stimulating hormone 
      (alpha-MSH) and single-minded 1 (SIM1) in hypothalamus arcuate nucleus (ARC) and 
      paraventricular nucleus (PVN), respectively, were significantly reduced in PND30 
      TCS-offspring compared to controls. The hypermethylation of CpG sites at the POMC 
      promoter was observed in PND30 TCS-offspring, while the concentration of serum 
      leptin was elevated and the level of STAT3 phosphorylation in ARC had no 
      significant difference from control. This study demonstrates that TCS exposure 
      during early/mid-gestation through the hypermethylation of the POMC promoter 
      reduces the expression of anorexigenic neuropeptides to cause the postnatal 
      hyperphagic obesity, leading to metabolic syndrome in adulthood.
FAU - Hua, Xu
AU  - Hua X
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, 210029, China.
AD  - Department of Physiology, Nanjing Medical University, Longmian Road 101, Nanjing, 
      210029, China.
FAU - Xiong, Jian-Wei
AU  - Xiong JW
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, 210029, China.
AD  - Department of Obstetrics and Gynecology, the First Affiliated Hospital of Nanjing 
      Medical UniversityNanjing Medical University, Nanjing, 210029, China.
FAU - Zhang, Ya-Jie
AU  - Zhang YJ
AD  - Department of Physiology, Nanjing Medical University, Longmian Road 101, Nanjing, 
      210029, China.
FAU - Cao, Xin-Yuan
AU  - Cao XY
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, 210029, China.
FAU - Sun, Peng
AU  - Sun P
AD  - Department of Biochemistry and Molecular Biology, Nanjing Medical University, 
      Nanjing, 210029, China.
FAU - Wu, Jie
AU  - Wu J
AD  - Department of Obstetrics and Gynecology, the First Affiliated Hospital of Nanjing 
      Medical UniversityNanjing Medical University, Nanjing, 210029, China. 
      wujiemd@126.com.
FAU - Chen, Ling
AU  - Chen L
AUID- ORCID: 0000-0003-4557-8511
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, 210029, China. lingchen@njmu.edu.cn.
AD  - Department of Physiology, Nanjing Medical University, Longmian Road 101, Nanjing, 
      210029, China. lingchen@njmu.edu.cn.
LA  - eng
GR  - 81671253/National Natural Science Foundation of China/International
GR  - 81471157/National Natural Science Foundation of China/International
GR  - 2014CB943303/National 973 Basic Research Program of China/International
GR  - BE2016765/Natural Science Foundation of Jiangsu Province (CN)/International
GR  - 2017NJMU006/Science and Technology Development Foundation of Nanjing Medical 
      University/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181030
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 4NM5039Y5X (Triclosan)
RN  - 581-05-5 (alpha-MSH)
RN  - 66796-54-1 (Pro-Opiomelanocortin)
SB  - IM
MH  - Animals
MH  - Arcuate Nucleus of Hypothalamus/drug effects/physiology
MH  - DNA Methylation/drug effects
MH  - Eating/drug effects
MH  - Epigenesis, Genetic/drug effects
MH  - Female
MH  - Gene Expression Regulation, Developmental/drug effects
MH  - Hyperphagia/chemically induced/*complications/genetics
MH  - Insulin Resistance
MH  - Male
MH  - Obesity/*etiology/genetics
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Pro-Opiomelanocortin/*genetics/metabolism
MH  - Promoter Regions, Genetic
MH  - Triclosan/*toxicity
MH  - Weight Gain/drug effects
MH  - alpha-MSH/biosynthesis
OTO - NOTNLM
OT  - DNA methylation
OT  - Hyperphagia
OT  - Hypothalamic proopiomelanocortin
OT  - Obesity
OT  - Triclosan (TCS)
EDAT- 2018/11/01 06:00
MHDA- 2020/05/19 06:00
CRDT- 2018/11/01 06:00
PHST- 2018/03/22 00:00 [received]
PHST- 2018/10/23 00:00 [accepted]
PHST- 2018/11/01 06:00 [pubmed]
PHST- 2020/05/19 06:00 [medline]
PHST- 2018/11/01 06:00 [entrez]
AID - 10.1007/s00204-018-2338-1 [pii]
AID - 10.1007/s00204-018-2338-1 [doi]
PST - ppublish
SO  - Arch Toxicol. 2019 Feb;93(2):547-558. doi: 10.1007/s00204-018-2338-1. Epub 2018 
      Oct 30.