Document Detail


Oleic acid stimulates system A amino acid transport in primary human trophoblast cells mediated by toll-like receptor 4.
MedLine Citation:
PMID:  23275648     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Obese women have an increased risk to deliver large babies. However, the mechanisms underlying fetal overgrowth in these pregnancies are not well understood. Obese pregnant women typically have elevated circulating lipid levels. We tested the hypothesis that fatty acids stimulate placental amino acid transport, mediated via toll-like receptor 4 (TLR4) and mammalian target of rapamycin (mTOR) signaling pathways. Circulating NEFA levels and placental TLR4 expression were assessed in women with varying prepregnancy body mass index (BMI). The effects of oleic acid on system A and system L amino acid transport, and on the activation of the mTOR (4EBP1, S6K1, rpS6), TLR4 (IĸB, JNK, p38 MAPK), and STAT3 signaling pathways were determined in cultured primary human trophoblast cells. Maternal circulating NEFAs (n = 33), but not placental TLR4 mRNA expression (n = 16), correlated positively with BMI (P < 0.05). Oleic acid increased trophoblast JNK and STAT3 phosphorylation (P < 0.05), whereas mTOR activity was unaffected. Furthermore, oleic acid doubled trophoblast system A activity (P < 0.05), without affecting system L activity. siRNA-mediated silencing of TLR4 expression prevented the stimulatory effect of oleic acid on system A activity. Our data suggest that maternal fatty acids can increase placental nutrient transport via TLR4, thereby potentially affecting fetal growth.
Authors:
Susanne Lager; Francesca Gaccioli; Vanessa I Ramirez; Helen N Jones; Thomas Jansson; Theresa L Powell
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-30
Journal Detail:
Title:  Journal of lipid research     Volume:  54     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-13     Completed Date:  2013-09-03     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  725-33     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Amino Acids / metabolism
Biological Transport / drug effects,  genetics
Body Mass Index
Cell Survival / drug effects
Cells, Cultured
Fatty Acids, Nonesterified
Female
Humans
Oleic Acid / pharmacology*
Pregnancy
RNA, Small Interfering
Signal Transduction / drug effects,  genetics
TOR Serine-Threonine Kinases / genetics,  metabolism*
Toll-Like Receptor 4 / genetics,  metabolism
Trophoblasts / drug effects*,  metabolism*
Grant Support
ID/Acronym/Agency:
R01 DK089989/DK/NIDDK NIH HHS; R01-DK-089989/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Fatty Acids, Nonesterified; 0/RNA, Small Interfering; 0/Toll-Like Receptor 4; 2UMI9U37CP/Oleic Acid; EC 2.7.1.1/MTOR protein, human; EC 2.7.1.1/TOR Serine-Threonine Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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