Objective

Most studies routinely use overnight or 6 h of fasting before testing metabolic glucose homeostasis in mice. Other studies used empirically shorter fasting times (<6 h). We attempted to determine the shortest fasting time required for optimal insulin responsiveness while minimizing metabolic stress.

Methods

A course of fasting for up to 24 h (0, 2, 4, 6, 12, and 24 h) was conducted in C57Bl/6J male mice. Body weight, metabolic parameters, and insulin tolerance were measured in each experimental group. The organs were collected at the same time on separate occasions and glycogen and metabolic gene expression were measured in the liver and skeletal muscle.

Results

Our data show that blood glucose levels do not significantly change during a 6 h fast, while plasma insulin levels decrease to similar levels between 2 h and 6 h of fasting. During overnight (12 h) and 24 h fasts, a robust decrease in blood glucose and plasma insulin was observed along with a profound depletion in liver glycogen content. Insulin tolerance was comparable between baseline and 6 h fasts while 4 h and 6 h fasts were associated with a greater depletion of liver glycogen than 2 h fasts, impacting the glucose counter-regulatory response. Fasting induced progressive weight loss that was attenuated at thermoneutrality. Fasting longer than 4 h induced major body weight loss (>5%) and significant changes in catabolic gene expression in the liver and skeletal muscle.

Conclusion

Collectively, these data suggest that 2 h of fasting appears optimal for the assessment of insulin tolerance in mice as this duration minimizes major metabolic stress and weight loss.

中文翻译：

---

重新评估小鼠胰岛素耐受性测试的最佳禁食时间。

客观的

大多数研究通常在测试小鼠代谢葡萄糖稳态之前使用过夜或禁食 6 小时。其他研究根据经验使用较短的禁食时间（<6 小时）。我们试图确定最佳胰岛素反应所需的最短禁食时间，同时最大限度地减少代谢压力。

方法

在 C57Bl/6J 雄性小鼠中进行长达 24 小时（0、2、4、6、12 和 24 小时）的禁食过程。在每个实验组中测量体重、代谢参数和胰岛素耐受性。在不同的时间同时收集器官，并测量肝脏和骨骼肌中的糖原和代谢基因表达。

结果

我们的数据显示，在禁食 6 小时期间血糖水平没有显着变化，而血浆胰岛素水平在禁食 2 小时至 6 小时之间降至相似水平。在隔夜（12 小时）和 24 小时禁食期间，观察到血糖和血浆胰岛素显着下降，同时肝糖原含量显着减少。胰岛素耐受性在基线和禁食 6 小时之间相当，而与禁食 2 小时相比，禁食 4 小时和 6 小时与更大程度的肝糖原消耗相关，从而影响葡萄糖反调节反应。禁食引起的渐进式体重减轻在热中性时减弱。禁食时间超过 4 小时会导致体重大幅下降 (> 5%) 以及肝脏和骨骼肌中分解代谢基因表达的显着变化。

结论

总的来说，这些数据表明，禁食 2 小时似乎是评估小鼠胰岛素耐受性的最佳时间，因为这个持续时间可以最大限度地减少主要的代谢压力和体重减轻。