Morphological, biochemical, transcriptional and epigenetic responses to fasting and refeeding in intestine of Xenopus laevis.

Amphibians are able to survive for several months without food. However, it is unclear what molecular mechanisms underlie their survival. To characterize the intestinal responses to fasting and refeeding, we investigated morphological, biochemical, transcriptional and epigenetic changes in the intestine from adult male Xenopus laevis. Frogs were fed for 22 days, fasted for 22 days, or fasted for 21 days and refed for 1 day. Fasting reduced, and refeeding recovered partially or fully, morphological parameters (wet weight of the intestine, circumference of the epithelial layer and number of troughs in a villus-trough unit), activities of digestive enzymes and plasma biochemical parameters (glucose, triglycerides, cholesterol and free fatty acids). Reverse transcription-quantitative polymerase chain reaction analysis revealed overall suppression of the transcript levels by fasting, with various recovery rates on refeeding. Chromatin immunoprecipitation assays on the selected genes whose transcript levels declined with fasting and recovered quickly with refeeding, showed several euchromatin marks in histone (acetylation and methylation) and RNA polymerase II modifications (phosphorylation) with fasting, and returned to the feeding levels by refeeding. The mRNA levels of these genes responded to fasting and refeeding to greater extents than did the pre-mRNA levels, suggesting the involvement of post-transcriptional regulation. Our results demonstrate that the X. laevis intestine may undergo overall metabolic suppression at least at the transcriptional level to save energy during fasting and quickly recovered to moderate nutritional deficiency by refeeding, and suggest that these dietary responses of the intestine are epigenetically and post-transcriptionally regulated.