Clock genes regulate the feeding schedule-dependent diurnal rhythm changes in hexose transporter gene expressions through the binding of BMAL1 to the promoter/enhancer and transcribed regions

Abstract

The expression of hexose transporter genes (SGLT1, GLUT5 and GLUT2) in mice with ad libitum feeding under light (7:00–19:00)–dark (19:00–7:00) cycle gradually increased from a basal level at 7:00 and reached a maximum at 19:00, coinciding with the start of dark phase feeding. The peaks of these gene expressions were shifted to 7:00 in mice that were subjected to a restricted feeding schedule from 9:00 to 17:00. The expression of BMAL1, a transcription factor driving the central feedback loop of the clock genes, was followed by the increase of hexose transporter gene expressions. The expressions of Per1-3, genes related to negative regulation of BMAL1, were the highest at or just after the time of maximal expression of the hexose transporter genes in both the group fed ad libitum and the restricted feeding group. Furthermore, chromatin immunoprecipitation assays revealed that the binding of BMAL1 to the promoter and/or transcribed regions of hexose transporters and Per 2 genes was associated with changes in their expressions. These results suggest that diurnal changes in expression of hexose transporter genes depend on the feeding schedule and are directly regulated by a feedback loop of clock genes.