Around 1.5 billion people worldwide are overweight or affected by obesity. They are at risk cardiovascular disease and related metabolic and inflammatory disturbances. While the links between being over-weight and the clinical conditions associated with adiposity are not clear, recent research shows it may influence DNA methylation.
Work carried out by researchers involved in the EU-funded IHEALTH-T2D project has fed into a new report that shines a light on the relationship between DNA methylation and body mass index. Genetic association analyses show that changes in DNA methylation are predominantly the result of adiposity, rather than being its cause.
The study found that, in many tissues, methylation loci are enriched for functional genomic features. The research, recently published in Nature, shows that sentinel methylation markers identify gene expression signatures at 38 loci. These loci identify the genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. The research also shines light on the relationship between type 2 diabetes and DNA methylation, showing that disturbances in methylation predict the future development of the condition.
The study considered 5 387 people of both European and Asian ancestry – populations known to be at risk from high body masses and related metabolic conditions. Methylation in genomic DNA from blood was quantified: blood was chosen for the analysis as it is a metabolically active tissue and has a key role to play both in inflammatory and cardiovascular conditions affecting those with high BMI.
Inflammatory and hormonal disturbances in the adipocytes of obese people contribute to insulin resistance and other metabolic consequences. To assess the relation of their observations in blood to other metabolically relevant tissues, researchers compared methylation levels at 187 loci in blood, subcutaneous and omental fat, liver, muscle, spleen and pancreas. Mean methylation levels at the 187 loci correlate moderately to strongly between the tissues.
They found that, after correction, 120 of the CpG sites (regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide) show directional consistency for association with BMI in both adipose tissue and blood, whereas 91 sites are associated with BMI in adipose tissue. This supports the view that methylation levels in blood are related to methylation patterns in other tissues at the CpG sites examined.
Results of the research provide new insights into the impact of adiposity on our biologic pathways and may give rise to new strategies for the prediction and prevention of type 2 diabetes and other conditions relating to obesity.
For more information, please see:
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