Does obesity lead to effects on the epigenome?

Obesity is associated with a number of adverse effects on health including insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease (Figure 1B). In this recent started programme of work we are using techniques such as DNA immunoprecipitation and ion torrent sequencing (Figure 2) to study the role of DNA methylation (5-methylcytosine, 5mC) and hydroxymethylation (5-hydroxymethylcytosine, 5hmC) in obesity and its common sequelae.

Research Methods and Objectives

 Liver pathology A. Healthy liver. B. NAFLD.
Figure 1. Liver pathology A. Healthy liver. B. NAFLD.

Some of our work has focussed on NAFLD, which encompasses a spectrum of liver disease. Simple steatosis involves hepatic lipid accumulation without inflammation or hepatocellular damage and is considered relatively benign; however it can progress to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis, and up to 27% of those with cirrhosis will develop hepatocellular carcinoma. The progression from NAFLD, through NASH, fibrosis and cirrhosis is highly variable between individuals and is influenced by both genes and environmental factors with only a minority of individuals reaching end-stage liver disease and/or developing HCC. Such inter-individual variability, coupled with a lack of understanding of the mechanisms underpinning the progression of NAFLD makes prognosis and patient stratification difficult and has limited the development of reliable biomarkers of risk and effective therapeutic interventions. We hope that our work in this area, in collaboration with Richard Meehan and David Haymay help in the identification of biomarkers and the development of novel therapeutics.

Profiling 5mC and 5hmC using ion torrent sequencing.
Figure 2. Profiling 5mC and 5hmC using ion torrent sequencing.

Related Researchers

Amanda Drake

Nicholas Morton

William Cawthorn

Project funded by

British Heart Foundation

Wellcome Trust

Edinburgh & Lothians Health Foundation