Effect of feeding behavior on circadian regulation of endothelin expression in mouse colon

AimsThe function, regulation and gene expression of the endothelin (ET) system in the intestine is not well understood. We investigated the dependence on feeding schedule and biological clock of the regulation of ET-1 gene expression in mouse colon.Main methodsMice were fed freely, fasted for 48 h and re-fed after fasting.Key findingsWhere indicated ET-1 gene expression was highest in the colon compared with other tissues examined in fasted mice. Fasting increased the level, while maintaining the rhythmicity, of ET-1 gene expression in epithelial colonic tissue. Re-feeding, however, decreased ET-1 gene expression and suppressed rhythmic oscillation, and the rhythmicity also changed for gene expression for circadian clocks, period-1 and period-2 (Per1 and Per2). Furthermore, the decrease in ET-1 gene expression induced by re-feeding was blocked by pre-treatment with hexamethonium and atropine. The daily change in ET-1 gene expression in colon, which depends on feeding schedule via the autonomic nervous system, is synchronized with peripheral circadian oscillators under conditions of free feeding and fasting but not re-feeding. The decrease in ET-1 gene expression in the proximal colon induced by re-feeding occurs via the nervous system.SignificanceET-1 plays an important physiological role, which is dependent on feeding behavior.

92