Effect of ω-3 supplementation on placental lipid metabolism in overweight and obese women

Am J Clin Nutr. 2016 Apr;103(4):1064-72. doi: 10.3945/ajcn.115.124651.


Background: The placentas of obese women accumulate lipids that may alter fetal lipid exposure. The long-chain omega-3 fatty acids (n–3 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 n–3 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 n–3 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 n–3 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 proliferator–activated 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 n–3:n–6 ratio (representing the n–3 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 n–3-supplemented women than in those in the placebo group (P < 0.05), but no differences in the ponderal index were observed. Supplementation of n–3 significantly decreased FA esterification in isolated trophoblasts without affecting FA oxidation.

Conclusion: Supplementing overweight and obese women with n–3 FAs during pregnancy inhibited the ability of the placenta to esterify and store lipids. This trial was registered at clinicaltrials.gov as NCT00957476.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Body Mass Index
  • Dietary Supplements
  • Docosahexaenoic Acids / administration & dosage*
  • Docosahexaenoic Acids / blood
  • Double-Blind Method
  • Eicosapentaenoic Acid / administration & dosage*
  • Eicosapentaenoic Acid / blood
  • Female
  • Humans
  • Lipid Metabolism / drug effects*
  • Obesity
  • Overweight
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Placenta / drug effects
  • Placenta / metabolism*
  • Pregnancy
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Trophoblasts / drug effects*
  • Trophoblasts / metabolism
  • Young Adult


  • PPAR gamma
  • RNA, Messenger
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid

Associated data

  • ClinicalTrials.gov/NCT00957476