Not so fast: Paradoxically increased variability in the glucose tolerance test due to food withdrawal in continuous glucose-monitored mice.
Not so fast: Paradoxically increased variability in the glucose tolerance test due to food withdrawal in continuous glucose-monitored mice.
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DOI：
10.1016/j.molmet.2023.101795
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发表时间：
2023-11
影响因子：
8.1
通讯作者：
Banks, Alexander S.
中科院分区：
文献类型：
--
作者：
Rubio, William B.;Cortopassi, Marissa D.;Ramachandran, Deepti;Walker, Samuel J.;Balough, Elizabeth M.;Wang, Jiefu;Banks, Alexander S.
关键词：
本研究旨在确定禁食对葡萄糖耐量试验重现性的影响。由于动物喂养行为的个体差异，代谢和行为实验前禁食动物被广泛接受，以减少临床前啮齿动物模型的葡萄糖和代谢参数的受试者间差异。减少变异性对于初始代谢物水平可能影响实验干预程度的研究尤为重要，但禁食也会施加可能扭曲感兴趣变量的压力。一种这样的干预是葡萄糖耐量试验（GTT），其测量外源性葡萄糖推注后的最大反应和恢复。我们试图研究禁食如何影响个体小鼠对GTT的反应。使用同步连续葡萄糖监测（CGM）和间接热量测定法，我们定量的血糖，体力活动，体温，代谢率，和食物消耗水平在一分钟到一分钟的基础上在成年雄性小鼠4周。我们测试了4小时或18小时禁食对GTT的影响，以检查在光照或黑暗光周期中食物戒断的影响。还在未植入CGM探针的其他小鼠中进行了4小时禁食研究。与我们的预期相反，在光照期间禁食4小时，促进了动物间代谢率、体力活动、体温、血糖和葡萄糖耐量变化的矛盾增加。这种高血糖和高代谢表型促进皮质酮水平升高，并且与对食物剥夺的行为应激反应一致，即使在喂养良好的小鼠中也是如此。我们发现，小鼠经历了18小时的快速进入麻木，冬眠样的状态。除了低体温和代谢率外，嗜睡还与葡萄糖水平有关，葡萄糖水平比随意进食的小鼠低56 mg/dl。此外，麻木的时间会影响对GTT的反应。我们的研究结果表明，在葡萄糖耐量测试之前禁食小鼠，也许其他实验，可能会产生与预期效果相反的效果，禁食可能会增加而不是减少实验变异性。自由采食的小鼠维持血糖水平的严格控制。与随意获取食物的小鼠相比，禁食增加了葡萄糖耐量试验的变化。在白天禁食小鼠增加葡萄糖水平、代谢率、体力活动和体温。在黑暗中长时间禁食会使小鼠进入昏睡状态。
This study was performed to determine the effect of fasting on reproducibility of the glucose tolerance test. Due to individual variation in animal feeding behaviors, fasting animals prior to metabolic and behavioral experiments is widely held to reduce inter-subject variation in glucose and metabolic parameters of preclinical rodent models. Reducing variability is especially important for studies where initial metabolite levels can influence the magnitude of experimental interventions, but fasting also imposes stress that may distort the variables of interest. One such intervention is the glucose tolerance test (GTT) which measures the maximum response and recovery following a bolus of exogenous glucose. We sought to investigate how fasting affects the response of individual mice to a GTT. Using simultaneous continuous glucose monitoring (CGM) and indirect calorimetry, we quantified blood glucose, physical activity, body temperature, metabolic rates, and food consumption levels on a minute-to-minute basis in adult male mice for 4 weeks. We tested the effects of a 4-h or 18-h fast on the GTT to examine the effect of food withdrawal in light or dark photoperiods. Studies were also performed with 4-h fasting in additional mice without implanted CGM probes. Contrary to our expectations, a 4-h fast during the light photoperiod promotes a paradoxical increase in inter-animal variation in metabolic rate, physical activity, body temperature, glycemia, and glucose tolerance. This hyperglycemic and hyper-metabolic phenotype promotes increased corticosterone levels and is consistent with a behavioral stress response to food deprivation, even in well-fed mice. We find that mice undergoing an 18-h fast entered torpor, a hibernation-like state. In addition to low body temperature and metabolic rate, torpor is also associated with glucose levels 56 mg/dl lower than those seen in mice with ad libitum access to food. Moreover, the time spent in torpor affects the response to a GTT. Our results suggest fasting mice before glucose tolerance testing, and perhaps other experiments, can have the opposite of the intended effect where fasting can increase, rather than decrease, experimental variability. Ad libitum mice maintain tight control of blood glucose levels. Fasting increases the variation in glucose tolerance testing compared to mice with ad libitum access to food. Fasting mice in the daytime increases glucose levels, metabolic rate, physical activity, and body temperature. Prolonged fasting in the dark photoperiod drives mice into torpor.
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影响因子：
5.8
作者：
Kennard, Matilda R.;Nandi, Manasi;Chapple, Sarah;King, Aileen J.
通讯作者：
King, Aileen J.
影响因子：
4.8
作者：
Korstanje, Ron;Ryan, Jennifer L.;Rizzo, Stacey J. Sukoff
通讯作者：
Rizzo, Stacey J. Sukoff
DOI：
10.1086/physzool.52.2.30152564
发表时间：
1979-01-01
期刊：
PHYSIOLOGICAL ZOOLOGY
影响因子：
--
作者：
HUDSON, JW;SCOTT, IM
通讯作者：
SCOTT, IM
DOI：
10.1152/ajpendo.90617.2008
发表时间：
2008-12-01
影响因子：
5.1
作者：
Andrikopoulos, Sofianos;Blair, Amy R.;Proietto, Joseph
通讯作者：
Proietto, Joseph
影响因子：
64.8
作者：
Douglass, Amelia M.;Resch, Jon M.;Lowell, Bradford B.
通讯作者：
Lowell, Bradford B.