Obesity is major challenge for healthcare worldwide and is linked to increased risk for type 2 diabetes and cardiovascular disease. However not all obese individuals are equally vulnerable and it has long been appreciated that central obesity (an excess of visceral fat) comprises a major risk factor for disease. It is also well established that adipose tissue from different parts of the body displays distinct biochemical properties, with biological profiles of subcutaneous and visceral fat being clearly distinguishable. It is likely that the biological mechanisms that govern these differences are, in part, responsible for rendering visceral fat a risk factor for disease. Given the need to understand the critical differences between adipose depots, the project I propose aims to identify key differences in the biology of subcutaneous and visceral fat, by addressing the fraction of genetic variants that contribute to this through a regulatory effect. To achieve this, mRNA will be extracted from subcutaneous and visceral adipose tissue from an initial sample of 50 individuals and will be sequenced using next generation sequencing. DNA will be extracted from lymphoblastoid cell lines from the same individuals and will be genotyped. Expression quantitative trait loci with an impact on cis gene expression will be identified through association of single nucleotide polymorphism genotypes with expression levels. Furthermore, chromatin will be extracted from subcutaneous and visceral fat from five individuals, and regions of open chromatin will be identified through formaldehyde-assisted isolation of regulatory elements. Integrating data on regulatory variation and open chromatin is an important way forward. This approach allows formulation of hypotheses regarding function outside of coding regions and is likely to lead to the identification of genetic variants that have a role in influencing susceptibility to obesity-related disorders.
Fields of science
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