Programmed cell death in rat intestine: Effect of feeding and fasting

Background: The regulation of intestinal cell death by luminal factors is poorly understood. The objectives of this study were to determine whether a diurnal rhythm of intestinal apoptosis exists, and to determine the role that feeding and fasting play in this process. Methods: Mucosal apoptotic death was measured in fed and 24-h fasted rats and at various times after feeding by DNA fragmentation and in situ immunohistochemical staining (TUNEL). Results: In 24-h fasted rats, 32% of total mucosal DNA was fragmented as compared to 9% in fed animals. In both jejunal and ileal segments, the fragmented DNA exhibited characteristic apoptotic DNA ladders on agarose gels. Immunohistochemical staining revealed significant location of apoptotic cells at the upper third of the intestinal villus. In the duodenum, DNA fragmentation at 6-12h post feeding was 20% and decreased to 4% at 24 h. In comparison, DNA fragmentation in the jejunum and ileum was low from 0 to 6 h post feeding (2%-9%) and significantly increased at 12 h (18% versus 12%) and 24 h (30% versus 32%), respectively. These results are consistent with a temporal relationship between percent fragmented DNA and time after feeding with greater cell death at longer fasting period. A postprandial rhythm of DNA fragmentation was evident in the jejunum and ileum, in which fragmentation was at a peak between 0900 h and 1200 h. Conclusion: Collectively, the data show that initiation of apoptosis in apical enterocytes is coincident with cessation of feeding and commencement of fasting, and is consistent with a rhythm of programmed cell death in these cells that parallels the cyclical pattern of feeding and fasting.