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

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 docosahexahenoic acid (DHA), neuroprostanes, arachidonic acid (AA), 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.

Sphingolipids and acylcarnitines are altered in placentas from women with gestational diabetes mellitus

“…This was not confirmed by our data, despite the fact that all women in the GDM group were overweight/obese. This observation was consistent with findings from our previous study, which showed that placentas from pregnant people with pre-gestational obesity did not present signs of lipid accumulation (33) . Therefore, our data indicate that obesity, whether aggravated or not by GDM, is not associated with increased placental lipid accumulation in well-controlled cohorts of women receiving nutritional counselling and insulin therapy.…”

Sex Specificities of Human Placental Adaptive Changes: The Influence of Maternal Obesity

“…Therefore, one can expect maternal dyslipidemia in obese women to alter the lipid composition of the placenta itself. Surprisingly, various studies have not revealed any differences in placental total lipid content or lipoprotein lipase mRNA expression between obese and nonobese women [61][62][63]. Nevertheless, it has been reported that maternal obesity was associated with (i) low placental FATP1 mRNA expression and a low proportion of saturated FAs in the placenta from obese women, (ii) low placental FABP1 mRNA expression and an elevated placental content of polyunsaturated free FAs, and (iii) elevated FA translocase FAT/CD36 mRNA expression and thus a higher placental content of long-chain polyunsaturated FAs, which have essential structural and functional roles in fetal development [61,63].…”

Early life programming of health and disease: The long‐term consequences of obesity in pregnancy

“…This may promote atherogenesis in the placental vessels (associated with pre‐eclampsia) and disrupt steroid hormone production. Obesity impacts upon fatty acid transport by the placenta and promotes an inflammatory response 111 . The capacity of the placenta to store fatty acids is limited with obesity, resulting in greater mobilisation into the foetal compartment 112 …”

“…Obesity impacts upon fatty acid transport by the placenta and promotes an inflammatory response. 111 The capacity of the placenta to store fatty acids is limited with obesity, resulting in greater mobilisation into the foetal compartment. 112 Clues with respect to the mechanism of programming by maternal obesity may be gained from studies of GDM because the long-term health of offspring exposed to GDM is largely the same as that observed with maternal obesity, although obesity can occur without GDM and vice versa.…”