Endocrine Abstracts

Background: Evidences show that maternal vitaminB12 deficiency at periods of development influence metabolic status and degree of metabolic syndrome of the offspring into adulthood. VitaminB12 is required for the synthesis of methionine, which is the precursor of S-adenosyl-methionine, a key methyl donor for DNA methylation. So vitaminB12 deficiency might cause methylation changes, which are thought to alter gene expression of regulatory factors and could result in adverse metabolic phenotypes. Our recent study showed that low maternal vitaminB12 was associated with adverse cord blood lipid profile and higher BMI which provided the clue to explore the link between the adiposity marker, leptin, and vitaminB12. We hypothesize that maternal B12 might program leptin levels in-utero. Therefore we investigated whether maternal B12 levels associate with leptin in maternal adipose tissue, placental tissue and cord blood.

Methods: Paired maternal venous and cord blood samples (n=91), adipose tissue (n=42) and placental tissue (n=83) were collected at delivery. Serum vitaminB12 was determined by electro-chemiluminescent immunoassay. Leptin levels were measured by ELISA. To assess the underlying mechanism, human pre-adipocyte cell line (Chub-S7) was differentiated in various B12 concentrations (1) Control: (B12-500 nM); (2) LowB12 (0.15 nM) (3) Control + methylation inhibitor (AZ): (B12-500 nM +5-Aza-dC-200 nM).

Results: B12 deficiency (<150 pmol/l) was common (mothers-40%; neonates-29%). In regression analysis, adjusted for likely confounders, maternal B12 independently associated with neonatal leptin (β=−0.662; P=0.002; R²=12.7%). Leptin gene expression was higher in adipose tissue and placental tissue from mothers with low B12. Leptin gene was higher in adipocytes (Chubs-S7) cultured with low B12 (0.15 nM) and treated with normal B12 (500 nM) in the presence of methylation inhibitor (5-Aza-dC).

Conclusion: Our study highlights that low maternal B12 associates with higher leptin in cord blood, maternal adipose tissue and placental tissue, suggesting leptin gene could represent a mechanism of adverse programming either in the placental tissue or maternal adipose tissue.