Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, France.
Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, France; Toulouse University Hospitals, Department of Clinical Biochemistry, Toulouse, France.
Mol Metab. 2020 Dec;42:101058. doi: 10.1016/j.molmet.2020.101058. Epub 2020 Jul 31.
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.
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.
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.
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.
大多数研究在检测小鼠代谢葡萄糖稳态时通常会让其隔夜或禁食 6 小时。其他研究则使用经验证的更短禁食时间（<6 小时）。我们试图确定在最小化代谢应激的情况下，获得最佳胰岛素反应所需的最短禁食时间。
在 C57Bl/6J 雄性小鼠中进行长达 24 小时的禁食（0、2、4、6、12 和 24 小时）。在每个实验组中测量体重、代谢参数和胰岛素耐量。在不同时间点分别收集器官，并测量肝脏和骨骼肌中的糖原和代谢基因表达。
我们的数据表明，在 6 小时禁食期间血糖水平没有显著变化，而在 2 小时和 6 小时禁食期间，血浆胰岛素水平下降到相似水平。在 overnight（12 小时）和 24 小时禁食期间，观察到血糖和血浆胰岛素显著下降，同时肝脏糖原含量明显耗尽。胰岛素耐量在基线和 6 小时禁食之间相当，而 4 小时和 6 小时禁食与 2 小时禁食相比，肝脏糖原消耗更多，影响了葡萄糖的代偿反应。禁食引起渐进性体重减轻，在体温中性时减轻。禁食时间超过 4 小时会导致体重明显减轻（>5%），并导致肝脏和骨骼肌中分解代谢基因表达发生重大变化。
综上所述，这些数据表明，2 小时的禁食似乎是评估小鼠胰岛素耐量的最佳选择，因为这种持续时间最小化了主要的代谢应激和体重减轻。
