Metabolomic analysis of C2C12 myoblasts induced by the transcription factor FOXO1

Abstract

The transcription factor FOXO1 is considered to play roles in the regulation of energy metabolism in various tissues. To determine the metabolic changes occurring due to FOXO1 activation, we analyzed the metabolic profile of C2C12 myoblasts expressing a FOXO1-estrogen receptor fusion protein using capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry (CE-TOFMS). In FOXO1-activated cells, the metabolite levels during glycolysis are higher and the gene expression of pyruvate dehydrogenase kinase, an enzyme that inhibits glucose utilization, is increased. In addition, the metabolite levels of numerous amino acids are decreased, with increased gene expression of branched chain amino acid metabolism enzymes. Our results suggest that FOXO1 suppresses glucose utilization and promotes the use of proteins/amino acids as energy sources in muscle cells, potentially during starvation.