Insulin resistance is associated with epigenetic and genetic regulation of mitochondrial DNA in obese humans

摘要

BackgroundMitochondrial alterations have been observed in subjects with metabolic disorders such as obesity and diabetes. Studies on animal models and cell cultures suggest aberrant glucose and lipid levels, and impaired insulin signaling might lead to mitochondrial changes. However, the molecular mechanism underlying mitochondrial aberrance remains largely unexplored in human subjects. ResultsHere we show that the mitochondrial DNA copy number (mtDNAn) was significantly reduced (6.9-fold lower, p 30). The reduction of mtDNAn was strongly associated with insulin resistance (HOMA-IR: ?0.703, p ConclusionsThe reduction of mtDNAn in obese human subjects is associated with insulin resistance and may arise from increased D-loop methylation, suggesting an insulin signaling-epigenetic-genetic axis in mitochondrial regulation.