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Lipid Lipid-
- Immune crosstalk
Immune crosstalk at the Maternal at the Maternal-
- Fetal Interface
For non commercial use ONLY at the Maternal Sylvie Hauguel-de - - PowerPoint PPT Presentation
For non commercial use ONLY at the Maternal Sylvie Hauguel-de - - PowerPoint PPT Presentation
Lipid- -Immune crosstalk Immune crosstalk Lipid at the Maternal- -Fetal Interface Fetal Interface For non commercial use ONLY at the Maternal Sylvie Hauguel-de Mouzon, PhD Case Western Reserve University, Cleveland, USA What makes the
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Lean OW & Obese
p
Insulin (U/ml) 6.3 ± 3.7 14.3 ± 5.6
<0.001
Leptin (ng/ml) 13.1 ± 9.1 35.1 ± 20.5
0.001
IL-6 (ng/ml) 1.2 ± 0.4 3.2 ± 3.7
0.05
CRP(mg/dl) 0.4 ± 0.3 0.7 ± 0.4
0.03
TNF-alpha (pg/ml) Adiponectin (g/ml) 1.9 ± 1.3 11.6 ± 1.3 1.8 ± 0.8 8.4 ± 1.2
ns 0.001
Inflammatory Exposome in pregnancy with obesity
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macrophages invade the maternal adipose tissue and the placental stroma
CD 68 CD 68
PLACENTA ADIPOSE TISSUE
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PCA of all microbial communities
first trimester third trimester postpartum
- bese
- verweight
normal weight
2012 2012
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Cani & Delzenne 2009
inflammation inflammation inflammation
Dietary exposome impacts gut microbiota
LPS
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Lipopolysaccharide (LPS) structure
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TLR4
2006, Jason K. Kim
Toll-like Receptor 4 inflammatory signals
LPS
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plasma (EU/ml)
Increased LPS in maternal plasma in term Pregnancy
Basu, Hauguel-de Mouzon Obesity 2010
Obese Lean
0.0 0.50 1.0 0.25 0.75 p=0.004
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Toll Like Receptor 4 links innate immunity and fatty acid–induced insulin resistance Shi, Flier J. Clin. Invest. 2006 Fat uses a TOLL-road to connect inflammation and diabetes Kim J Cell Metab. 2006
The lipid-inflammation connection
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What makes the baby fat ?
Lipids – the concepts
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Hypothesis
Hyperlipemic envrionment at the maternal-fetal interface increases placental inflammation
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High plasma TG Fatty Acids Cholesterol (apoB)
Dietary exposome: lipids
saturated
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Meyer et al 2012
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Structural Similarity between LPS and Fatty Acids
FA
Oleic acid (C18:1) Palmitic acid (C16:0)
C14:0 C12:0
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TLR4 Toll-like Receptor 4 inflammatory signals
IL6-TNF-IL8
MyD88
NFB
CD14
LPS
Lipid A
Jason K. Kim, 2006 TLRs play a fundamental role in pathogen recognition and activation of innate immunity
Fatty Acid
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CONTROL PALMITATE 24hrs
Cytokeratine TLR4 HUMAN TERM PRIMARY TROPHOBLAST cells
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Can maternal lipid diet elicit placental inflammation
mono- unsaturated FA OLEATE C18:1 saturated FA PALMITATE C16:0
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TLR4 gene expression in cultured human trophoblast cells
4 8 12 16 CTL BSA LPS Oleate Palmitate (n=5)
mRNA fold change
1
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TLR4 activation in cultured human trophoblast cells
TLR4 mRNA fold change
Effect of LPS
1 2 3 4 CTL 6h 24h
*
5 10 15 20 CTL 6h 24h 1
* *
PALMITATE
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Inflammatory cytokine response to palmitate but not oleate in cultured trophoblast cells
mRNA fold change over CTL
(n=5)
1
15 30 45 60 IL-6 IL-8 TNF-a LPS Oleate Palmitate
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TLR4 Cytokeratin Dapi
m
Placenta TLR4 localization
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Yang, Hauguel-de Mouzon (ongoing studies)
Placenta TLR4 mRNA
2 4 6
Lean Obese
Fold change vs basal
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