DNA methylation patterns in human adipose tissue in relation to diet and type 2 diabetes

Sammanfattning: Type 2 diabetes (T2D) is a common metabolic disease and its prevalence is increasing worldwide. Adipose tissue plays an important role in metabolic processes. Environmental factors may affect metabolic phenotypes and epigenetics may mediate this influence. We used Illumina 450k microarrays to study correlations between epigenetic patterns in human adipose tissue and environmental factors such as high-fat diets, impaired intrauterine environment and low birth weight as well as with type 2 diabetes.In study 1 we investigated whether the DNA methylation pattern in human adipose tissue is affected differently by a 7-week exposure to a diet high in either polyunsaturated fatty acids or saturated fatty acids. We found differences in methylation related to general fat overfeeding as well as between the two dietary groups.In study 2 we studied the effect of 5 days of overfeeding with a high fat diet on DNA methylation in adipose tissue compared to a control diet. The participants were either born with a normal or low birth weight and it allowed also to compare the effects of the diets on these two groups separately. There were differences in methylation between subjects born with a low compared with normal birth weight.In study 3 we used adipose tissue of a cohort of 14 monozygotic twin pairs discordant for type 2 diabetes in order to eliminate most of known confounding factors in comparing DNA methylation patterns as well as a case- control cohort for T2D. We found numerous differences in methylation in adipose tissue from subjects with T2D compared with controls, while less differences were found in the discordant twins.In study 4 we compared DNA methylation in adipose-derived stem and differentiated cells in subjects born with a low or normal birth weight. We found differences in gene expression in adipose-derived stem cells between low birth weight and normal birth weight groups but did not identify differences in methylation patterns possibly due to lack of statistical power.Overall, these studies contribute to a better understanding of the influence of environmental factors and type 2 diabetes on DNA methylation in human adipose tissue.