PMID- 30670847
OWN - NLM
STAT- MEDLINE
DCOM- 20200601
LR  - 20200601
IS  - 1476-5497 (Electronic)
IS  - 0307-0565 (Linking)
VI  - 43
IP  - 11
DP  - 2019 Nov
TI  - Mice exposed to maternal androgen excess and diet-induced obesity have altered 
      phosphorylation of catechol-O-methyltransferase in the placenta and fetal liver.
PG  - 2176-2188
LID - 10.1038/s41366-018-0314-8 [doi]
AB  - BACKGROUND/OBJECTIVES: Maternal obesity together with androgen excess in mice 
      negatively affects placental function and maternal and fetal liver function as 
      demonstrated by increased triglyceride content with dysfunctional expression of 
      enzymes and transcription factors involved in de novo lipogenesis and fat 
      storage. To identify changes in molecular pathways that might promote diseases in 
      adulthood, we performed a global proteomic analysis using a 
      liquid-chromatography/mass-spectrometry system to investigate total and 
      phosphorylated proteins in the placenta and fetal liver in a mouse model that 
      combines maternal obesity with maternal androgen excess. METHODS: After ten weeks 
      on a control diet (CD) or high fat/high sugar-diet, dams were mated with males 
      fed the CD. Between gestational day (GD) 16.5 and GD 18.5, mice were injected 
      with vehicle or dihydrotestosterone (DHT) and sacrificed at GD 18.5 prior to 
      dissection of the placentas and fetal livers. Four pools of female placentas and 
      fetal livers were subjected to a global proteomic analysis. Total and 
      phosphorylated proteins were filtered by ANOVA q < 0.05, and this was followed by 
      two-way ANOVA to determine the effect of maternal obesity and/or androgen 
      exposure. RESULTS: In placenta, phosphorylated ATP-citrate synthase was decreased 
      due to maternal obesity, and phosphorylated catechol-O-methyltransferase (COMT) 
      was differentially expressed due to the interaction between maternal diet and DHT 
      exposure. In fetal liver, five total proteins and 48 proteins phosphorylated in 
      one or more sites, were differentially expressed due to maternal obesity or 
      androgen excess. In fetal liver, phosphorylated COMT expression was higher in 
      fetus exposed to maternal obesity. CONCLUSION: These results suggest a common 
      regulatory mechanism of catecholamine metabolism in the placenta and the fetal 
      liver as demonstrated by higher phosphorylated COMT expression in the placenta 
      and fetal liver from animals exposed to diet-induced maternal obesity and lower 
      expression of phosphorylated COMT in animals exposed to maternal androgen excess.
FAU - Fornes, Romina
AU  - Fornes R
AD  - Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.
FAU - Manti, Maria
AU  - Manti M
AD  - Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.
FAU - Qi, Xiaojuan
AU  - Qi X
AD  - Department of Physiology, Qiqihar Medical University, Qiqihar, China.
FAU - Vorontsov, Egor
AU  - Vorontsov E
AD  - Proteomics Core Facility, University of Gothenburg, Gothenburg, Sweden.
FAU - Sihlbom, Carina
AU  - Sihlbom C
AD  - Proteomics Core Facility, University of Gothenburg, Gothenburg, Sweden.
FAU - Nystrom, Jenny
AU  - Nystrom J
AD  - Department of Physiology, Sahlgrenska Academy, University of Gothenburg, 
      Gothenburg, Sweden.
FAU - Jerlhag, Elisabet
AU  - Jerlhag E
AD  - Department of Pharmacology, Sahlgrenska Academy, University of Gothenburg, 
      Gothenburg, Sweden.
FAU - Maliqueo, Manuel
AU  - Maliqueo M
AD  - Endocrinology and Metabolism, Faculty of Medicine, West division, University of 
      Chile, Santiago, Chile.
FAU - Hirschberg, Angelica Linden
AU  - Hirschberg AL
AD  - Division of Obstetrics and Gynecology, Karolinska University Hospital, Solna, 
      Sweden.
FAU - Carlstrom, Mattias
AU  - Carlstrom M
AD  - Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.
FAU - Benrick, Anna
AU  - Benrick A
AD  - Department of Physiology, Sahlgrenska Academy, University of Gothenburg, 
      Gothenburg, Sweden.
AD  - School of Health and Education, University of Skovde, Skovde, Sweden.
FAU - Stener-Victorin, Elisabet
AU  - Stener-Victorin E
AUID- ORCID: 0000-0002-3424-1502
AD  - Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden. 
      elisabet.stener-victorin@ki.se.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190122
PL  - England
TA  - Int J Obes (Lond)
JT  - International journal of obesity (2005)
JID - 101256108
RN  - 0 (Dietary Sugars)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - EC 2.1.1.6 (Catechol O-Methyltransferase)
SB  - IM
MH  - Animals
MH  - *Catechol O-Methyltransferase/chemistry/drug effects/metabolism
MH  - Diet, High-Fat
MH  - Dietary Sugars
MH  - Dihydrotestosterone/*pharmacology
MH  - Female
MH  - Fetus/drug effects/enzymology
MH  - *Liver/drug effects/enzymology
MH  - Male
MH  - Mice
MH  - Obesity/*metabolism
MH  - Phosphorylation/drug effects
MH  - *Placenta/drug effects/enzymology
MH  - Pregnancy
EDAT- 2019/01/24 06:00
MHDA- 2020/06/02 06:00
CRDT- 2019/01/24 06:00
PHST- 2018/07/15 00:00 [received]
PHST- 2018/12/19 00:00 [accepted]
PHST- 2018/11/19 00:00 [revised]
PHST- 2019/01/24 06:00 [pubmed]
PHST- 2020/06/02 06:00 [medline]
PHST- 2019/01/24 06:00 [entrez]
AID - 10.1038/s41366-018-0314-8 [pii]
AID - 10.1038/s41366-018-0314-8 [doi]
PST - ppublish
SO  - Int J Obes (Lond). 2019 Nov;43(11):2176-2188. doi: 10.1038/s41366-018-0314-8. 
      Epub 2019 Jan 22.