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通过对慢性不可预知温和应激(CUMS)诱导的大鼠进行稳定同位素分辨代谢组学,对抑郁症中高速率和低效率的葡萄糖代谢有了新的认识。

A novel insight for high-rate and low-efficiency glucose metabolism in depression through stable isotope-resolved metabolomics in CUMS-induced rats.

作者信息

Tian Jun-Sheng, Zhao Yun-Hao, Ling-Hu Ting, Wu Wen-Ze, Wang Xian-Xian, Ji Cui, Zhao Wei-di, Han Yu-Mei, Qin Xue-Mei

机构信息

Modern Research Center for Traditional Chinese Medicine of Shanxi University, No.92, Wucheng Road, Taiyuan 030006, China; Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan 030006, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China.

Modern Research Center for Traditional Chinese Medicine of Shanxi University, No.92, Wucheng Road, Taiyuan 030006, China.

出版信息

J Affect Disord. 2023 Jun 15;331:121-129. doi: 10.1016/j.jad.2023.03.061. Epub 2023 Mar 21.

DOI:10.1016/j.jad.2023.03.061
PMID:36948469
Abstract

BACKGROUND

Existing research has suggested that depression results in disorders of glucose metabolism in the organism which causing insufficient energy supply. However, the overall changes in glucose metabolism that arise from depression have not been clarified.

METHODS

In this study, the depression-like behavior in chronically unpredictable mild stressed rats was investigated, and the fate of glucose was tracked through isotope tracing and mass spectrometry, with a focus on metabolite changes in cecal contents.

RESULTS

As indicated by the results, the isotopic results of cecal contents can indicate the metabolic end of the organism. Moreover, the TCA cycle activity was notably reduced, and the gluconeogenesis pathway was abnormally up-regulated in the CUMS-induced rats. The organism expedited other glucose metabolism pathways to make up for the insufficiency of energy. As a result, the activity of the inefficient glycolysis pathway was increased.

LIMITATIONS

Existing research has only investigated the metabolism of C-glucose, and lipids and proteins have been rarely explored.

CONCLUSIONS

The chronic unpredictable mild stress can inhibit the entry of pyruvate into mitochondria in SD rats, such that the activity of TCA is reduced, and insufficient energy supply is caused. The organism is capable of expediting other glucose metabolism rate pathways to make up for the insufficiency of energy, whereas it still cannot compensate for the loss of energy. As a result, CUMS-induced rats exhibited high-rate and low-efficiency glucose metabolism.

摘要

背景

现有研究表明,抑郁症会导致机体葡萄糖代谢紊乱,进而造成能量供应不足。然而,抑郁症引发的葡萄糖代谢的整体变化尚未明确。

方法

在本研究中,对慢性不可预测轻度应激大鼠的抑郁样行为进行了研究,并通过同位素示踪和质谱法追踪葡萄糖的去向,重点关注盲肠内容物中的代谢物变化。

结果

结果表明,盲肠内容物的同位素结果可指示机体的代谢终点。此外,在慢性不可预测轻度应激诱导的大鼠中,三羧酸循环活性显著降低,糖异生途径异常上调。机体加快了其他葡萄糖代谢途径以弥补能量不足。结果,低效糖酵解途径的活性增加。

局限性

现有研究仅研究了C-葡萄糖的代谢,对脂质和蛋白质的研究较少。

结论

慢性不可预测轻度应激可抑制SD大鼠丙酮酸进入线粒体,从而降低三羧酸循环活性,导致能量供应不足。机体能够加快其他葡萄糖代谢速率途径以弥补能量不足,但其仍无法弥补能量损失。结果,慢性不可预测轻度应激诱导的大鼠表现出高速率和低效率的葡萄糖代谢。

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