Modulation of circadian expression of D-site binding protein by the schedule of parenteral nutrition in rat liver



The aim of this study was to investigate the changes in the circadian rhythm of the expression of liver-specific genes caused by different schedules of parenteral nutrition (PN). Rats received PN continuously throughout the day or intermittently during the night or day for 7 days. They were examined for gene expression of D-site binding protein (DBP), albumin, and cytochrome P450 cholesterol 7α-hydroxylase (CYP7) in the liver. The nocturnal PN group showed circadian expression of DBP messenger RNA (mRNA) and protein with a peak at 10 PM, in the same manner as the control rats receiving normal chow feeding. However, the diurnal PN group showed inverted expression of DBP mRNA and protein with a peak at 10 AM. CYP7 mRNA levels exhibited good synchronization with the levels of DBP mRNA in all groups, whereas albumin mRNA levels did not show such synchronization. Gel mobility-shift assay disclosed that the binding activity of the nuclear extracts to the CYP7 gene promoter was changed by the PN schedule in accordance with the expression of CYP7 mRNA. The PN schedule modulates the circadian rhythm of DBP expression and may have an effect on hepatic bile acid formation through transcriptional regulation of the CYP7 gene.