Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: impact of liver methylation of the peroxisome proliferator-activated receptor γ coactivator 1α promoter.

摘要: Insulin resistance (IR) and mitochondrial dysfunction play a central role in the pathophysiology of nonalcoholic fatty liver disease (NAFLD). We hypothesized that genetic factors epigenetic modifications occurring contribute to IR phenotype. specifically examined whether are modified by hepatic DNA methylation peroxisome proliferator–activated receptor γ coactivator 1α (PPARGC1A) transcription factor A (TFAM) promoters, also evaluated (mtDNA) content is associated with NAFLD IR. studied biopsies obtained from patients case–control design. After bisulfite treatment DNA, we used methylation-specific polymerase chain reaction (PCR) assess putative three CpG PPARGC1A TFAM promoters. Liver mtDNA quantification using nuclear (nDNA) as reference was way real-time PCR. methylated DNA/unmethylated ratio correlated plasma fasting insulin levels homeostasis model assessment (HOMA-IR); inversely levels. promoter abundance messenger RNA. The mtDNA/nDNA significantly higher control livers compared livers. HOMA-IR, glucose, methylation. Conclusion: Our data suggest phenotype transcriptional activity show tight interaction, probably through modifications. Decreased concomitantly contributes peripheral (HEPATOLOGY 2010)