Metabolic programming: Role of micronutrient (B12) deficiency and associated epigenetic marks

The global epidemic of childhood obesity is a major public health issue. Although current adverse lifestyle (nutrition and physical inactivity) contributes to obesity, a growing body of evidence links early life nutritional adversity to the development of obesity and metabolic disorders in children. Emerging evidences show that deficiencies of key maternal micronutrients involved in the one-carbon metabolism (1-C) cause adverse metabolic programming. Vitamin B12 is needed for the synthesis of methionine, which is the precursor of S-adenosyl-methionine, a key methyl donor for DNA methylation.

Data from human longitudinal studies and animal models suggest a causative role for vitamin B12 in the development of insulin resistance, small for gestational age and metabolic syndrome phenotype in the offspring. Our preliminary analysis in white pregnant women showed B12 deficiency rates were 20% at 16-18 weeks of gestation and 40% at delivery. Maternal B12 predicts higher lipids in cord blood after controlling for maternal BMI and birth weight. Our findings therefore may represent a reflection of insulin resistance caused either by the dysfunctional placenta or adipose tissue.

Our study aims to investigate that low maternal B12 levels could alter epigenetic mechanisms either though methylation or miRNAs and could have profound effect on tissue-specific gene expression. This study will contribute in understanding the role of micronutrients on the health of the mother and their babies and would offer novel opportunities to reduce the risk of metabolic disease in next generation.
To test these hypotheses, the projects will provide unique opportunities to work with various techniques such as cell culture with different cell models, molecular cell biology – DNA, RNA isolation, reverse transcription, gene expression analysis using quantitative real time PCR (Q-PCR), protein characterisation using western blot, mass spectrometric analysis, methylation and miRNA analysis. The student will be embedded within a dynamic, vibrant and supportive research group to gain training in these techniques - cell culture, molecular biology and omics technologies.