Catalase overexpression and mitochondrial function in insulin resistant muscle cells

Abstract

We examined whether the reduction of mitochondrial capacity and insulin response imposed by the high availability of fatty acids are associated with an increase of intracellular hydrogen peroxide (H2O2). We investigated whether the oxidative stress induced by excess fatty acids can be reversed with improved antioxidant capacity through overexpression of catalase. The catalase gene was successfully transfected in skeletal muscle cells through pcDNA3 plamid as indicated by catalase mRNA and content (p<0.05). The H2O2 production was increased after palmitic acid treatment. This effect markedly reduced the citrate sintase activity as well as the mRNA levels of PGC1α (p<0.05). This effect was accompanied by a significantly reduction of p‐AKt which further was demonstrated to down regulate p‐CREB and PPAR‐β. In addition, oxygen consumption and uptake glucose were markedly reduced in the presence of palmitic acid (p<0.05). However, the catalase transfection was observed to prevent reduction of p‐AKt level which further was demonstrated to up regulate p‐CREB and PPAR‐β (p<0.05). Our results showed that fatty acid reduced the p‐AKt level. This effect was associated with a low p‐CREB level and consequently PGC1‐α transcription. The reduced mitochondrial oxygen consumption favored ROS production and insulin resistance. The catalase‐ induced effect on p‐AKt increased the oxygen consumption and glucose and fatty acid metabolism suggesting that mitochondrial biogenesis might be regulated by phosphorylated level of AKt.