Department for Developmental Origins of Disease (DDOD), Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Leibniz Institute for Resilience Research (LIR), Mainz, Germany.
Sci Rep. 2024 Oct 26;14(1):25511. doi: 10.1038/s41598-024-76310-3.
Chronic stress has been shown to induce hyperglycemia in both peripheral blood and the brain, yet the detailed mechanisms of glucose metabolism under stress remain unclear. Utilizing C-labeled glucose to trace metabolic pathways, our study investigated the impact of stress by chronic social defeat (CSD) on glucose metabolites in the liver and brain one week post-stress. We observed a reduction in C-enrichment of glucose metabolites in the liver, contrasting with unchanged levels in the brain. Notably, hepatic glycogen levels were reduced while lactate concentrations were elevated, suggesting lactate as an alternative energy source during stress. Long-term effects were also examined, revealing normalized blood glucose levels and restored glycogen stores in the liver three weeks post-CSD, despite sustained increases in food intake. This normalization is hypothesized to result from diminished glucagon levels leading to reduced glycogen phosphorylase activity. Our findings highlight a temporal shift in glucose metabolism, with hyperglycemia and glycogen depletion in the liver early after CSD, followed by a later phase of metabolic stabilization. These results underscore the liver's critical role in adapting to CSD and provide insights into the metabolic adjustments that maintain glucose homeostasis under prolonged stress conditions.
慢性应激已被证明会导致外周血和大脑中的高血糖，但应激下葡萄糖代谢的详细机制仍不清楚。本研究利用 C 标记的葡萄糖追踪代谢途径，研究了慢性社交挫败（CSD）对应激后一周肝脏和大脑中葡萄糖代谢物的影响。我们观察到肝脏中葡萄糖代谢物的 C 富集减少，而大脑中水平不变。值得注意的是，肝糖原水平降低，而乳酸浓度升高，表明乳酸是应激期间的替代能源。我们还研究了长期影响，发现 CSD 后三周血糖水平正常化，肝糖原储存恢复，尽管食物摄入量持续增加。据推测，这种正常化是由于胰高血糖素水平降低导致糖原磷酸化酶活性降低所致。我们的研究结果强调了葡萄糖代谢的时间变化，CSD 后早期肝脏出现高血糖和糖原耗竭，随后进入代谢稳定的后期阶段。这些结果突出了肝脏在适应 CSD 中的关键作用，并提供了对在长期应激条件下维持葡萄糖稳态的代谢调整的深入了解。
