Endocrine Abstracts

Background: Obesity-linked metabolic disorders are a worldwide health concern affecting about one third of women of reproductive age. The programming events in utero impact the risk of predisposition to obesity and metabolic diseases. Maternal B12 deficiency is associated with higher cord lipids. B12 has a potential epigenetic role and therefore may perpetuate an intergenerational cycle of obesity through its effects on placental function and fetal metabolism. Therefore, we hypothesize that B12 deficiency could affect placental lipid metabolism and may alter fetal lipid levels, potentially influencing neonatal adiposity. Here, we assessed whether low B12 in human placental trophoblasts alters de novo fatty acid (FA) synthesis and oxidation.

Methods: Human trophoblastic choriocarcinoma cells (Bewo) were cultured using custom made Ham’s F12 media supplemented with sufficient (500nM-Control) or low concentrations of B12 media (25pM-low B12) until confluence was achieved. RNA isolation, cDNA synthesis and gene expression assays using RT-qPCR were employed to examine the expression of genes required for FA synthesis and oxidation.

Results: Placental trophoblasts cultured in low B12 showed significantly increased gene expression of (1) nuclear transcription factors regulating FA synthesis (SREBF1), oxidation (LDLR), adipogenesis (PPARγ, CEBPα), (2) de novo FA synthesis (ACLY, ACACA, FASN), FA elongation (ELOVL6), (3) triglyceride biosynthesis (GPAT, AGPAT, Lipin1, DGAT2) and (4) downregulated gene expression in FA oxidation (CPT1A, SLC25A2, ACADS, HADHB, HADHA) compared to control (P<0.05). We also observed deregulated expression of leptin, a major adipokine of placental lipid metabolism.

Conclusion: Our data provide evidence that low B12 potentially impacts lipid metabolism and deregulates leptin in placental trophoblasts. Thus, indicating that B12 deficiency could alter placental lipid levels which may lead to placental dysfunction and subsequent dyslipidemia in offspring. Future studies to elucidate the epigenetic mechanisms will support the development of effective interventions to optimize maternal metabolism, placental function and health of the offspring.