NRF‐1 and its target genes are increased by exercise: Potential role of NRF‐1 in type 2 diabetes

Nuclear respiratory factor (NRF)‐1 is a mitochondrial transcriptional factor whose function of late shown to be involved in glucose transport (Ramachandran et al., 2008, Baar et al., 2003) and set it as a potential therapeutic modality in the treatment and management of type 2 diabetes. In this study we sought to access NRF‐1 and its target genes expression during exercise which are crucial in glucose transport and lipid oxidation. Five to six weeks old male Wistar rats were exercised to identify the time points for optimum increase in the levels of NRF‐1 and its target genes. Gastrocnemius muscle was harvested after 0, 2, 4, 6, 8, 10, 12 and 15 hours (h) post exercise and non‐exercise rats (control). Primers were used to amplify the region of following genes: Nrf‐1, Glut 4, Carnitine palmitoyltransferase (Cpt‐1& Cpt‐2), Peroxisome proliferator‐activated receptor gamma co‐activator 1 (Pgc‐1), Mef2a, Acetyl‐CoA Carboxylase‐1 (Acc‐1). Relative mRNA expression was normalized to actin reference gene. Cpt‐1, Nrf‐1, Mef2a, Glut4, Cpt2 and Pgc‐1 showed 2.5, 8, 1.2, 4.1, 4.6, 3.5 fold increases respectively after 8h post exercise compared to control whereas Acc‐1 showed 3.1 fold decrease in gene expression ratio after 6 h post exercise compared to control. NRF‐1 binding to cpt‐1 and mef‐2 increased 3 and 3.5 fold respectively 6h post exercise compared to controls. These results show that NRF‐1 was increased by exercise and also its binding to target genes which has huge implication in emeliorating type 2 diabetes and insulin resistance.