PMID- 28677406
OWN - NLM
STAT- MEDLINE
DCOM- 20181115
LR  - 20200225
IS  - 1933-7205 (Electronic)
IS  - 1933-7191 (Print)
IS  - 1933-7191 (Linking)
VI  - 25
IP  - 3
DP  - 2018 Mar
TI  - Tropomyosin Receptor Kinase B Agonist, 7,8-Dihydroxyflavone, Improves 
      Mitochondrial Respiration in Placentas From Obese Women.
PG  - 452-462
LID - 10.1177/1933719117716776 [doi]
AB  - Maternal obesity negatively impacts the placenta, being associated with increased 
      inflammation, decreased mitochondrial respiration, decreased expression of 
      brain-derived neurotrophic factor (BDNF), and its receptor, tropomyosin receptor 
      kinase B (TRKB). TRKB induction by 7,8-dihydroxyflavone (7,8-DHF) improves energy 
      expenditure in an obesity animal model. We hypothesized that TRKB activation 
      would improve mitochondrial respiration in trophoblasts from placentas of obese 
      women. Placentas were collected from lean (pre-pregnancy BMI < 25) and obese 
      (pre-pregnancy BMI > 30) women at term following cesarean section delivery 
      without labor. Cytotrophoblasts were isolated and plated, permitting 
      syncytialization. At 72 hours, syncytiotrophoblasts (STs) were treated for 1 hour 
      with 7,8-DHF (10 nM-10 M), TRKB antagonists (ANA-12 (10 nM-1 M), Cyclotraxin B (1 
      nM-1M)), or vehicle. Mitochondrial respiration was measured using the XF24 
      Extracellular Flux Analyzer. TRKB, MAPK, and PGC1alpha were measured using Western 
      blotting. Maternal obesity was associated with decreased mitochondrial 
      respiration in STs; however, 7,8-DHF increased basal, ATP-coupled, maximal, spare 
      capacity, and nonmitochondrial respiration. A 10 muM dose of 7,8-DHF reduced spare 
      capacity in STs from lean women, with no effect on other respiration parameters. 
      7,8-DHF had no effect on TRKB phosphorylation; however, there was a 
      concentration-dependent decrease of p38 MAPK phosphorylation and increase of 
      PGC1alpha in STs from obese, but not in lean women. TRKB antagonism attenuated 
      ATP-coupled respiration, maximal respiration, and spare capacity in STs from lean 
      and obese women. 7,8-DHF improves mitochondrial respiration in STs from obese 
      women, suggesting that the obese phenotype in the placenta can be rescued by TRKB 
      activation.
FAU - Prince, Calais S
AU  - Prince CS
AD  - 1 Center for Pregnancy and Newborn Research, Department of Obstetrics and 
      Gynecology, University of Texas Health Science Center San Antonio, TX, USA.
FAU - Maloyan, Alina
AU  - Maloyan A
AD  - 1 Center for Pregnancy and Newborn Research, Department of Obstetrics and 
      Gynecology, University of Texas Health Science Center San Antonio, TX, USA.
AD  - 2 Knight Cardiovascular Institute, Oregon Health & Science University, Portland, 
      OR, USA.
FAU - Myatt, Leslie
AU  - Myatt L
AD  - 1 Center for Pregnancy and Newborn Research, Department of Obstetrics and 
      Gynecology, University of Texas Health Science Center San Antonio, TX, USA.
AD  - 3 Deparment of Obstetrics and Gynecology, School of Medicine, Oregon Health & 
      Science University, Portland, OR, USA.
LA  - eng
GR  - R01 HD076259/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20170705
PL  - United States
TA  - Reprod Sci
JT  - Reproductive sciences (Thousand Oaks, Calif.)
JID - 101291249
RN  - 0 (7,8-dihydroxyflavanone)
RN  - 0 (Flavanones)
RN  - 0 (Membrane Glycoproteins)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (tropomyosin-related kinase-B, human)
SB  - IM
MH  - Adult
MH  - Energy Metabolism/drug effects
MH  - Female
MH  - Flavanones/*pharmacology
MH  - Humans
MH  - Membrane Glycoproteins/*agonists/metabolism
MH  - Mitochondria/*drug effects/metabolism
MH  - Obesity/*metabolism
MH  - Phosphorylation
MH  - Placenta/*drug effects/metabolism
MH  - Pregnancy
MH  - Receptor, trkB/*agonists/metabolism
MH  - Young Adult
PMC - PMC6343218
OTO - NOTNLM
OT  - mitochondrial respiration
OT  - neurotrophin
OT  - obesity
OT  - placenta
COIS- Declaration of Conflicting Interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2017/07/06 06:00
MHDA- 2018/11/16 06:00
PMCR- 2019/03/01
CRDT- 2017/07/06 06:00
PHST- 2017/07/06 06:00 [pubmed]
PHST- 2018/11/16 06:00 [medline]
PHST- 2017/07/06 06:00 [entrez]
PHST- 2019/03/01 00:00 [pmc-release]
AID - 10.1177_1933719117716776 [pii]
AID - 10.1177/1933719117716776 [doi]
PST - ppublish
SO  - Reprod Sci. 2018 Mar;25(3):452-462. doi: 10.1177/1933719117716776. Epub 2017 Jul 
      5.