Decreased Fatty Acid Transporter FABP1 and Increased Isoprostanes and Neuroprostanes in the Human Term Placenta: Implications for Inflammation and Birth Weight in Maternal Pre-Gestational Obesity.

Livia Belcastro,Claire Vigor,Marcelle A Saraiva,Gabriela D A Pinto,Camille Oger,Julian L Griffin,Carolina S Ferreira,Fátima L C Sardinha,Carla Lai,Tatiana El-Bacha,Graham J Burton,Jean-Marie Galano,Antonio Murgia,Thierry Durand,Alexandre G Torres,Daniela B Mucci

doi:10.3390/nu13082768

Abstract

The rise in prevalence of obesity in women of reproductive age in developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health. Placental lipid metabolism is disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism in women with pre-gestational obesity as a sole pregnancy complication and compared it to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidised products of docosahexaenoic (DHA) and arachidonic acid (AA), respectively, neuroprostanes and isoprostanes. Despite no overall signs of lipid accumulation, DHA and AA levels in placentas from obese women were, respectively, 2.2 and 2.5 times higher than those from lean women. Additionally, a 2-fold increase in DHA-derived neuroprostanes and a 1.7-fold increase in AA-derived isoprostanes were seen in the obese group. These changes correlated with a 70% decrease in placental FABP1 protein. Multivariate analyses suggested that neuroprostanes and isoprostanes are associated with maternal and placental inflammation and with birth weight. These results might shed light on the molecular mechanisms associated with altered placental fatty acid metabolism in maternal pre-gestational obesity, placing these oxidised fatty acids as novel mediators of placental function.

Highlights

Maternal pre-gestational obesity and excessive gestational weight gain affect shortand long-term health of both the mother and her child [1]
(r = −0.60; p = 0.054; Figure 2G). These results suggest that fatty acid binding protein-1 (FABP1) might play a role in placental handling of these fatty acids and that the decrease in its content might have an impact in the availability and signalling properties of Eicosapentaenoic acid (EPA), DHA, and arachidonic acid (AA), in particular
Negative correlations were found between the sum of neuroprostanes and isoprostanes and FABP1, but only the latter reached statistical significance (r = −0.42; p = 0.17 for neuroprostanes, Figure 3D, and r = −0.66; p = 0.02 for isoprostanes, Figure 3F). These results suggest that the decrease in FABP1 protein observed in placentas from women with pre-gestational obesity is, to some degree, associated with the increase in neuroprostanes and isoprostanes observed in these placentas

Summary

Introduction

Maternal pre-gestational obesity and excessive gestational weight gain affect shortand long-term health of both the mother and her child [1]. Long chain polyunsaturated fatty acids, in particular docosahexaenoic acid (DHA) and arachidonic acid (AA), have specific roles in membrane composition and the development of the retina, and are the major components of the white matter of the brain. They are of paramount importance to proper neural and visual development and cognitive function [8,9,10,11]. Ex vivo placental perfusion data [12] and in vivo kinetics of 13 C-fatty acids [13] show that maternal–fetal 13 C-labelled lipid transfer is very low (1–6%), implying that lipid metabolism and handling by the placenta are strictly controlled and that these mechanisms are possibly major players in the allocation of fatty acids to fetal organs [14,15]

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Results

Discussion

Conclusion