Serum Citrulline Levels Exhibit Circadian Variation and Fluctuations in Relation to Food Intake in Mice.

backgroundPlasma citrulline is a nonessential amino acid synthesized almost exclusively by enterocytes of the small intestine. Correlation between post-operative plasma citrulline levels and remnant small bowel mass and function has led to its use as a simple biomarker of functional intestinal mass in adults and children, with a proposed prognostic value for achieving enteral autonomy in the setting of intestinal failure. While it is standard to measure fasting levels in humans, the optimal timing of blood draws in relation to food intake and time of day has not been standardized and is poorly studied in animal models. We hypothesize that serum citrulline levels vary both throughout the day and with relation to food intake in mice.

methodsSerum citrulline levels were measured from 12 C57BL/6 mice (6 - 9 weeks old) in the mornings and evenings, either after

resultsAfter withholding chow for 8 - 12 h, serum citrulline levels were significantly greater in the morning compared to levels drawn in the evening. When mice were allowed

conclusionsSerum citrulline levels exhibit circadian variation and fluctuations in relation to food intake in mice, without apparent concurrent changes in enterocyte mass. There was no diurnal variation of serum citrulline levels in fed mice whereas fasted mice had significantly higher levels of serum citrulline in the morning compared to the evening. These findings underscore the paramount importance of consistent sample collection strategies in the setting of translational research.