A study presented at this year's annual meeting of the European Association for the Study of Diabetes (EASD) shows that exercise can chemically alter the genes associated with obesity or type 2 diabetes (T2D) that are present in human adipose (fat) tissue. The study is by Dr Tina Rönn, Lund University, Malmö, Sweden.
Obesity is a predictor for type 2 diabetes (T2D), which in combination with genetic and life-style factors suggests a central role for fat (adipose) tissue in the pathogenesis of T2D. Environmental factors potentially change the DNA chemically without actually changing the sequence of DNA (epigenetic effects), and recent studies point towards epigenetic mechanisms to be involved in the regulation of genes important for glucose metabolism and the pathogenesis of T2D. In this study, Ronn and colleagues looked at how the DNA methylation pattern (how much the DNA had been chemically altered) in adipose tissue had changed in healthy men before and after a six months exercise intervention.
The study involved a supervised exercise intervention performed in 23 men with a mean age of 37 years and BMI of 28 kg/m2 (overweight) at inclusion. Subcutaneous fat biopsies were obtained before and after the intervention and DNA methylation studied using complex analytical techniques.
The clinical and metabolic outcomes of the exercise intervention was a significant decrease in waist circumference, waist/hip ratio, diastolic blood pressure and resting heart rate, whereas a significant increase was seen for exercise capacity and 'good' cholesterol (HDL cholesterol).
The researchers found 24 sites located close to 18 of the candidate genes for obesity with a difference in DNA methylation in adipose tissue in response to the exercise intervention. Additionally, two of those genes (CPEB4 and SDCCAG8) showed significant changes in mRNA expression after exercise (meaning that the activity of these particular genes was significantly changed by exercise).
Among the T2D candidate genes, 45 sites in 21 different genes were differentially methylated in fat tissue before versus after exercise. Of note, 10 of these sites mapped to KCNQ1 and 6 sites mapped to TCF7L2-important since TCF7L2 is the gene showing the highest genetic association with type 2 diabetes. A simultaneous change in mRNA expression was seen for four of the T2D candidate genes where mRNA expression decreased while DNA methylation increased in adipose tissue in response to exercise, meaning that again, the activity of these particular genes was significantly changed by exercise.
Dr Ronn concludes: "In this work we present a link between exercise and altered adipose tissue DNA methylation in candidate genes for obesity or T2D. This study highlights the dynamic feature of DNA methylation, described using a genome-wide analysis in human adipose tissue before and after exercise."
She adds: "Since we also observed DNA methylation changes in genes important for fat metabolism, which indicates increased fat uptake in response to exercise, these genes could potentially be a target for future drugs."