Epigenetic regulation of human fat distribution – relationship to metabolic dysfunction

Preferential accumulation of fat in the lower body (gluteal) exhibits protective behaviour against metabolic diseases, but the molecular mechanism behind this is sparsely understood.

Through the proposed project, I will test the possibility of epigenetic drivers in adipose tissue determining fat distribution. The project will be conducted at Oxford University, Metabolic research group for a period of three years with Prof. Fredrik Karpe.

I will utilise abdominal and gluteal RNA-Seq and whole-genome methylome data along with detailed characterization (e.g. genetic, anthropometric, biochemistry) from a recalled cohort (n=160) of Oxford Biobank.

A wide range of statistical and bioinformatics methods including causal inference, machine learning, and multi-omics integration will be exploited to (i) investigate the association between methylome and transcriptome (ii) investigate the methylome and transcriptome associations with regional fat distribution, adipocyte size, and metabolic phenotypes.

The results will be tested in external datasets (UK Biobank and IMI DIRECT).

Overall, the findings are expected to elucidate the epigenetic, molecular, and functional mechanisms behind the protective behaviour of the gluteal adipose tissue in contrast to the detrimental role of abdominal adipose tissue in relation to metabolic system diseases.

In long term, these findings can help with managing obesity, uncoupling it from metabolic diseases, and developing new therapeutic approaches.