Plasma DNA: A window to obesity
Obesity and associated diseases are significant health burdens across the world. Australia is not immune to this global epidemic with nearly 2 in 3 adults classified as overweight or obese. Subsequently, the incidence of type 2 diabetes associated with obesity has risen dramatically. Since 1989 the rate of diabetes has more than tripled in the Australian population, rising from 1.5% of the total population to 4.7% in 2015. The impact of diabetes is particularly high in disadvantaged groups. The lowest socioeconomic quintile suffer diabetes at a rate almost twice that of the highest socioeconomic group and for Indigenous Australians the rate is almost three times that of the general population. There is an urgent need for new methods of managing metabolic disease.
New evidence implicates inflammation in visceral fat tissue (the deep fat surrounding organs) as a key event in the progression of diabetes. Often this increase in visceral fat is accompanied with an invasion of fat to the liver, so called “fatty liver”. The chronic inflammation in visceral fat due to obesity stimulates the production of signalling molecules that disrupt the normal immune system, triggering cell death and a measurable increase in ccfDNA. In the liver, this inflammation and damage caused by a buildup of fat eventually leads to the condition of Nonalcoholic steatohepatitis (NASH).
Using tissue specific DNA methylation patterns, we can determine the precise source ccfDNA and thereby create an indicator of metabolic health changes driven by central obesity. We are studying the epigenetic profiles of ccfDNA in obese and diabetic individuals with the aim to identify a circulating DNA methylation signature associated with poor metabolic health and the risk of Type II Diabetes Mellitus and Nonalcoholic steatohepatitis.