Clock genes regulate circadian rhythmical change of sglt1 gene expression according to feeding schedule through binding of BMAL1 on the promoter region

Abstract

Sodium‐D‐glucose cotransporter SGLT1 plays an important role in the absorption of glucose in the small intestine. To examine whether the circadian rhythmical expression of the intestinal sglt1 gene is regulated by clock genes, we determined the levels of mRNA and BMAL1 binding on the promoter regions of the sglt1 gene by real‐time RT‐PCR and chromatin immunoprecipitation assay, respectively, in the jejunum of mice receiving free access to diet and those with restricted feeding from 9:00 to 17:00 under light (7:00‐19:00)‐dark (19:00‐7:00) cycle. Jejunal expression of sglt1 gene gradually increased from 7:00, and reached a maximal level at 19:00 in mice with free access to diet. The peak was shifted to 7:00 in mice with restricted feeding schedule. The gene expression of bmal1, a transcription factor driving the central feedback loop of clock genes, displayed a maximal expression at the period when sglt1 gene expression started to increase. The gene expression of per1‐3, the clock genes coding negative regulators of BMAL1, was highest at or soon after the time of maximal expression of sglt1 gene in both groups. The binding of BMAL1 to the promoters of sglt1 and per2 genes was associated with their expressional changes. The results suggest that the circadian expressional change of sglt1 gene in the jejunum of mice which is cued by the feeding schedule is directly regulated by a feedback loop of clock genes.