Serum Citrulline Levels Exhibit Circadian Variation and Fluctuations in Relation to Food Intake in Mice
Serum Citrulline Levels Exhibit Circadian Variation and Fluctuations in Relation to Food Intake in Mice
复制标题
DOI：
10.14740/gr1146
复制
发表时间：
2019-04-01
影响因子：
1.5
通讯作者：
Cowles, Robert A.
中科院分区：
文献类型：
--
作者：
Park, Christine J.;Shaughnessy, Mattho P.;Cowles, Robert A.
背景：血浆瓜氨酸是一种非必需氨基酸，几乎完全由小肠的肠细胞合成。术后血浆瓜氨酸水平与残余小肠质量和功能之间的相关性使其被用作成人和儿童功能性肠质量的简单生物标志物，并具有在肠衰竭情况下实现肠自主性的预测价值。虽然测量人类的空腹水平是标准的，但与食物摄入量和一天中的时间相关的最佳抽血时间尚未标准化，并且在动物模型中研究得很少。我们假设血清瓜氨酸水平在一天中变化，并与食物intake in mice. Methods：血清瓜氨酸水平测定从12 C57 BL/6小鼠（6 - 9周龄）在早晨和晚上，无论是后随意进食或后8 - 12小时的访问水只。根据我们的机构动物护理和使用委员会（IA-CUC）关于存活程序可接受采血体积的指南，每一实验设置的采血间隔1周进行。在实验结束时，将小鼠安乐死，并收获小肠用于形态测量。使用Student t检验比较组平均值，假设P <0.05具有显著性。结果：禁食8 - 12小时后，早晨血清瓜氨酸水平显著高于晚上的水平。当允许小鼠自由进食时，早晨和晚上采集的血清瓜氨酸水平无显著差异。在不同的实验条件下，绒毛高度检测没有差异。结论：血清瓜氨酸水平表现出昼夜变化和波动的关系，在小鼠的食物摄入量，没有明显的并发变化肠上皮细胞质量。进食小鼠的血清瓜氨酸水平没有昼夜变化，而禁食小鼠早晨的血清瓜氨酸水平明显高于晚上。这些发现强调了在翻译研究中一致的样本收集策略的重要性。
Background: Plasma 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.Methods: Serum citrulline levels were measured from 12 C57BL/6 mice (6 - 9 weeks old) in the mornings and evenings, either after ad libitum food intake or after 8 - 12 h of access to water only. Blood draws for each experimental set-up were performed 1 week apart according to our Institutional Animal Care and Use Committee (IA-CUC) guidelines for acceptable blood collection volumes for survival procedures. At the end of the experiment, mice were euthanized and small intestine was harvested for morphometric measurements. Group means were compared using Student's t-test with significance assumed for P < 0.05.Results: After 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 ad libitum chow, there was no significant difference in serum citrulline levels drawn in the morning compared to the evening. There was no difference detected in villus height across the different experimental conditions.Conclusions: Serum 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.