Gluconeogenesis: re-evaluating the FOXO1-PGC-1alpha connection.
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-1alpha act synergistically to stimulate the expression of genes in the gluconeogenesis pathway and propose that PGC-1alpha 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-1alpha. Our results indicate that the transcriptional interaction between FOXO1 and PGC-1alpha is indirect.
Schilling
Marcia M
MM
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, Tennessee 37232, USA.
Oeser
James K
JK
Boustead
Jared N
JN
Flemming
Brian P
BP
O'Brien
Richard M
RM
D000818:Animals; D045744:Cell Line, Tumor; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005943:Gluconeogenesis / Q000235:genetics*; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D020218:Response Elements / Q000235:genetics
D051858:Forkhead Transcription Factors; D016601:RNA-Binding Proteins; D005952:Glucose-6-Phosphatase