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

• Published in: Journal of affective disorders 2023-06, Vol.331, p.121-129
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Animals; Cecal contents; Chronic unpredictable mild stress; Depression; Disease Models, Animal; Glucose; High-rate and low-efficiency glucose metabolism; Liquid chromatography-mass spectrometry; Metabolomics - methods; Rats; Rats, Sprague-Dawley; Stable isotope-resolved metabolomics; Stress, Psychological - metabolism
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2023.03.061

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. 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. 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. Existing research has only investigated the metabolism of 13C-glucose, and lipids and proteins have been rarely explored. 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. [Display omitted] •Stable isotope tracer metabolomics revealed the glucose metabolism disorder caused by depression in CUMS-induced rats.•Blocked TCA cycle leads to an increase in the activity of inefficient glucose metabolic pathways.•The overall glucose metabolism caused by depression is characterized by high rate and low efficiency.•Improving the overall glucose metabolism caused by depression is a potential method to treat depression.