Fatty acid transporter expression and regulation is impaired in placental macrovascular endothelial cells in obese women

Abstract

Objective: Fetal fatty acid (FA) delivery is ultimately controlled by placental transport. Focus has been the maternal-placental interface, but regulation at the feto-placental interface is unknown.

Methods: Placental macrovascular endothelial cells (EC) (n = 4/group) and trophoblasts (TB) (n = 5/group) were isolated from lean (pregravid BMI <25 kg/m²) and obese (body mass index (BMI) > 30) women. Fatty acid transporters FAT/CD36, FABPpm, FATP4, FABP 3, 4 and 5, PLIN2 and PPARα, δ, γ expression, was measured in EC and TB. Transporter response to 24 h palmitate (PA) was assessed.

Results: mRNA expression of FABP3, 4, 5 and PPARγ was 2- to 3-fold reduced in EC of obese versus lean women (p < .03), but not in TB. Protein level of FABPpm was 20% lower in obese (p < .05). Palmitate (PA) up-regulated CD36, FABP3, FABP4, and PLIN2 gene expression by 3- to 4-fold in lean but not obese EC (p < .05), while PA increased FABP4 and PLIN2 in lean and obese TB, and FABP5 in lean (p < .05) EC. PA exposure up-regulated peroxisome proliferator activated receptors (PPARs) 2-fold in lean and obese EC (p < .05), but not in TB.

Conclusions: In obese women, FA transporter expression is lower in placental EC, but not TB, and less sensitive to saturated FA, compared to lean women. FA transport may be regulated at the feto-placental interface.

Keywords:

• Fatty acid transporters
• placenta
• trophoblasts
• endothelial cells
• obesity

Acknowledgements

We gratefully acknowledge Luciana Gomes and Jasmin Strutz from Medical University of Graz for technical help with placental macrovascular endothelial cells isolation and validation. Additional thanks to Patrick Catalano and Sylvie Hauguel-de Mouzon for critical reading of the manuscript. XY contributed to study design, acquisition and analysis of data and manuscript drafting. PG and GCR contributed to imaging, study design and manuscript drafting. MH and MVCN helped with qPCR and WB. JM recruited patients and obtained biological samples. PO’T-G performed statistical analysis, manuscript drafting and was responsible for the integrity of the work as a whole. All authors gave their approval to the final version of the manuscript.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by the National Institutes of Health [R00HD062841].