Abstract
BackgroundThe gut is a major energy consumer, but a comprehensive overview of the adaptive response to fasting is lacking. Gene-expression profiling, pathway analysis, and immunohistochemistry were therefore carried out on mouse small intestine after 0, 12, 24, and 72 hours of fasting.ResultsIntestinal weight declined to 50% of control, but this loss of tissue mass was distributed proportionally among the gut's structural components, so that the microarrays' tissue base remained unaffected. Unsupervised hierarchical clustering of the microarrays revealed that the successive time points separated into distinct branches. Pathway analysis depicted a pronounced, but transient early response that peaked at 12 hours, and a late response that became progressively more pronounced with continued fasting. Early changes in gene expression were compatible with a cellular deficiency in glutamine, and metabolic adaptations directed at glutamine conservation, inhibition of pyruvate oxidation, stimulation of glutamate catabolism via aspartate and phosphoenolpyruvate to lactate, and enhanced fatty-acid oxidation and ketone-body synthesis. In addition, the expression of key genes involved in cell cycling and apoptosis was suppressed. At 24 hours of fasting, many of the early adaptive changes abated. Major changes upon continued fasting implied the production of glucose rather than lactate from carbohydrate backbones, a downregulation of fatty-acid oxidation and a very strong downregulation of the electron-transport chain. Cell cycling and apoptosis remained suppressed.ConclusionThe changes in gene expression indicate that the small intestine rapidly looses mass during fasting to generate lactate or glucose and ketone bodies. Meanwhile, intestinal architecture is maintained by downregulation of cell turnover.
Highlights
The gut is a major energy consumer, but a comprehensive overview of the adaptive response to fasting is lacking
Effects of fasting on intestinal structure To study the effect of fasting on the small intestine, 6 week old male FVB mice were subjected to fasting for 0, 12, 24 and 72 h and analyzed by means of immunohistochemistry and gene expression profiling (Figure 1A)
Since the time intervals between the measurements were not identical, it was important to define a common denominator to determine the rate of body weight loss
Summary
The gut is a major energy consumer, but a comprehensive overview of the adaptive response to fasting is lacking. A comprehensive view of the adaptive response of the intestine to maintain its integrity during food deprivation is, still lacking. Such insight is highly relevant to better understand the mucosal atrophy that develops as an undesirable sequel of parenteral nutrition [5]. To obtain a more comprehensive understanding of the effects of short-term and prolonged food deprivation, we performed a microarray-based study of the effects of fasting in the mouse small intestine (SI). Most of the early responses to fasting were transient, peaking at 12 hours after food withdrawal, whereas the late response became more pronounced with the duration of fasting
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
