ABSTRACT
BACKGROUND: The placentas of obese women accumulate lipids that may alter fetal lipid exposure. The long-chain omega-3 fatty acids (n3 FAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) alter FA metabolism in hepatocytes, although their effect on the placenta is poorly understood. OBJECTIVE: We aimed to investigate whether n3 supplementation during pregnancy affects lipid metabolism in the placentas of overweight and obese women at term. DESIGN: A secondary analysis of a double-blind randomized controlled trial was conducted in healthy overweight and obese pregnant women who were randomly assigned to DHA plus EPA (2 g/d) or placebo twice a day from early pregnancy to term. Placental FA uptake, esterification, and oxidation pathways were studied by measuring the expression of key genes in the placental tissue of women supplemented with placebo and n3 and in vitro in isolated trophoblast cells in response to DHA and EPA treatment. RESULTS: Total lipid content was significantly lower in the placentas of overweight and obese women supplemented with n3 FAs than in those supplemented with placebo (14.14 ± 1.03 compared with 19.63 ± 1.45 mg lipid/g tissue; P < 0.05). The messenger RNA expression of placental FA synthase (FAS) and diacylglycerol O-acyltransferase 1 (DGAT1) was negatively correlated with maternal plasma enrichment in DHA and EPA (P < 0.05). The expression of placental peroxisome proliferatoractivated receptor γ (r = −0.39, P = 0.04) and its target genes DGAT1 (r = −0.37, P = 0.02) and PLIN2 (r = −0.38, P = 0.04) significantly decreased, with an increasing maternal n3:n6 ratio (representing the n3 status) near the end of pregnancy. The expression of genes that regulate FA oxidation or uptake was not changed. Birth weight and length were significantly higher in the offspring of n3-supplemented women than in those in the placebo group (P < 0.05), but no differences in the ponderal index were observed. Supplementation of n3 significantly decreased FA esterification in isolated trophoblasts without affecting FA oxidation. CONCLUSION: Supplementing overweight and obese women with n3 FAs during pregnancy inhibited the ability of the placenta to esterify and store lipids. This trial was registered at clinicaltrials.gov as NCT00957476.
Subject(s)
Docosahexaenoic Acids/administration & dosage , Eicosapentaenoic Acid/administration & dosage , Lipid Metabolism/drug effects , Placenta/metabolism , Trophoblasts/drug effects , Adult , Body Mass Index , Dietary Supplements , Docosahexaenoic Acids/blood , Double-Blind Method , Eicosapentaenoic Acid/blood , Female , Humans , Obesity , Overweight , PPAR gamma/genetics , PPAR gamma/metabolism , Placenta/drug effects , Pregnancy , RNA, Messenger/genetics , RNA, Messenger/metabolism , Trophoblasts/metabolism , Young AdultABSTRACT
OBJECTIVE: The purpose of this study was to assess whether maternal factors that are associated with fetal lean and fat mass differ between sexes. STUDY DESIGN: Secondary analysis of a prospective cohort that delivered by scheduled cesarean section from 2004-2013. Maternal blood was collected before surgery for metabolic parameters. Placental weight and neonatal anthropometrics were measured within 48 hours. Anthropometric differences between sexes were assessed with the Student t test. Multiple stepwise regression analysis assessed the relationship between independent maternal variables and neonatal lean body mass (LBM), fat mass (FM), or percentage of fat as dependent variables in male and female infants combined and separately. RESULTS: We analyzed 360 women with normal glucose tolerance and a wide range of pregravid body mass index (16-64 kg/m(2)) and their offspring (male, 194; female, 166). Male infants had more FM (mean difference, 40 ± 18 g; P = .03) and LBM (mean difference, 158 ± 34 g; P < .0001) than female infants. Percentage of body fat and measured maternal variables did not differ between sexes. In both sexes, placental weight had the strongest correlation with both neonatal LBM and FM, which accounted for 20-39% of the variance. In male infants, maternal height, body mass index, and weight gain were significant predictors of both lean and fat mass. In female infants, plasma interleukin-6 and C-reactive protein, respectively, were associated independently with percentage of body fat and LBM. CONCLUSION: Our findings suggest that the body composition and inflammatory environment of the mother modulate the metabolic fitness of neonates, as predicted by fat and lean mass, in a sex-specific manner.