Gluconeogenesis Re-evaluating the FOXO1-PGC-1α connection

Arising from: P. Puigserver et al. Nature 423, 550-555 (2003).Increased expression of the gene encoding the enzyme glucose-6-phosphatase (G6Pase) contributes to the increased production of glucose by the liver that occurs in individuals with diabetes. Puigserver et al. show that the transcription factor FOXO1 and the transcriptional co-activator PGC-1α act synergistically to stimulate the expression of genes in the gluconeogenesis pathway and propose that PGC-1α acts, in part, directly through FOXO1. Here we show that FOXO1 is neither required nor sufficient for the stimulation of G6Pase-luciferase fusion gene expression by PGC-1α. Our results indicate that the transcriptional interaction between FOXO1 and PGC-1α is indirect.