Placental F4-Neuroprostanes and F2-Isoprostanes are altered in gestational diabetes mellitus and maternal obesity.

We investigated whether gestational diabetes mellitus (GDM) associated with maternal obesity modifies the placental profile of F4-Neuroprostanes and F2-Isoprostanes, metabolites of non-enzymatic oxidation of docosahexaenoic acid (DHA) and arachidonic acid (AA), respectively. Twenty-five placental samples were divided into lean (n=11), obesity (n=7) and overweight/obesity+GDM (n=7) groups. F4-Neuroprostanes and F2-Isoprostanes were higher in obesity compared to lean controls, but reduced to levels similar to lean women when obesity is further complicated with GDM. Lower content of F2-Isoprostanes suggests adaptive placental responses in GDM attenuating oxidative stress. However, low levels of placental F4-Neuroprostanes may indicate impaired DHA metabolism in GDM, affecting fetal development and offspring health. These results were not related to differences in placental content of DHA, AA and polyunsaturated fatty acids status nor to maternal diet or gestational weight gain. Placental DHA and AA metabolism differs in obesity and GDM, highlighting the importance of investigating the signalling roles of F4-Neuroprostanes and F2-Isoprostanes in the human term placenta.

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.

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.

Fatty acid profile of maternal and fetal erythrocytes and placental expression of fatty acid transport proteins in normal and intrauterine growth restriction pregnancies.

Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (-1, -2 and -4) and FABPs (-1 and -3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR.

Interesterified fat or palm oil as substitutes for partially hydrogenated fat in maternal diet can predispose obesity in adult male offspring.

BACKGROUND & AIMS: Palm oil (PO) and interesterified fat (IF) have been used to replace partially hydrogenated fat (PHF), which is rich in trans isomers, in processed foods. The purpose of this study was to investigate whether normolipidic diets containing PHF, IF, or PO consumed during pregnancy and lactation affect total body adiposity and adipose tissue morphology of adult offspring mice. METHODS: Four groups of female C57BL/6 mice were fed, during pregnancy and lactation, a control diet (control group, CG), a PHF diet (trans group, TG), a PO diet (PG group), or an IF diet (IG group). After weaning (at 21 days), male pups received the control diet for 70 days. Food intake and body weight were monitored in all groups throughout the experimental period. At 3 months of age, mice were sacrificed and the inguinal (IWAT), epididymal (EWAT), retroperitoneal (RPWAT), and mesenteric (MWAT) adipose fat pads were removed and weighed. Adiposity was quantified by micro computed tomography (micro-CT), and adipocyte areas and cell number were analyzed by histology. RESULTS: PG and IG offspring gained more weight than CG and TG groups (p < 0.01) during the first 10 weeks after weaning, resulting in higher final body weights (p < 0.05). IG mice and PG mice had respectively heavier EWAT and IWAT than TG and CG mice. Micro-CT scanning revealed that the total volumes of internal, external, and total fat depots were greater in IG animals, as compared to the other groups. Larger adipocyte areas were observed in EWAT and IWAT in IG and TG, respectively, in comparison to CG and PG mice. PG mice showed increased adipocyte numbers in IWAT. CONCLUSIONS: Maternal intake of IF and/or PO during pregnancy and lactation predisposes the offspring to the development of obesity in adult life in mice.