Systematic studies of the DNA methylation landscape and the related transcriptome of metabolic tissues from obese and/or type 2 diabetic patients show that DNA methylation is altered in metabolic diseases. Therefore, global epigenomic and transcriptomic analyses of human liver in various states of insulin resistance could offer valuable insight into the regulatory mechanisms involved in the pathogenesis of type 2 diabetes.
To better understand the molecular mechanisms underlying the development of hepatic insulin resistance and type 2 diabetes, Kirchner and colleagues perform genome-wide methylome and transcriptome analyses of liver from age-matched, non-obese and metabolically healthy, obese nondiabetic and obese type 2 diabetic men. They find key genes involved in hepatic glycolysis and de novo lipogenesis are hypomethylated and activated in obese non-diabetic and obese type 2 diabetic patients compared to non-obese control subjects. The results indicate that the epigenetic landscape in liver is altered in obesity, concomitant with an increased expression of genes involved in hepatic glycolysis and gluconeogenesis, as well as stearate biosynthesis. These genomic changes may contribute to the development of insulin resistance in obesity and type 2 diabetes.Full Text