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

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 . 1 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.