Testosterone regulates thymic remodeling by altering metabolic reprogramming in male rats

IF 2.1 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

General and comparative endocrinology Pub Date : 2024-01-06 DOI:10.1016/j.ygcen.2024.114448

Dong Li , Huan Yao , Yonghao Ren , Jiameng Shang , Xinfa Han , Xiaohan Cao , Tianzeng Song , Xianyin Zeng

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Abstract

The thymus is an energy-consuming organ, and its metabolism changes with atrophy. Testosterone regulates thymus remodeling (atrophy and regeneration). However, the characteristics of the energy metabolism during testosterone-mediated thymic atrophy and regeneration remain unclear. In this study, we demonstrated that testosterone ablation (implemented by immunocastration and surgical castration) induced global metabolic changes in the thymus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment for differential metabolites and metabolite set enrichment analysis for total metabolites revealed that testosterone ablation affected thymic glycolysis, glutamate metabolism, and fatty acid β-oxidation. Testosterone ablation-induced thymic regeneration was accompanied by attenuated glycolysis and glutamate metabolism and changed fatty acid composition and content. Testosterone supplementation in immunocastrated and surgically castrated rats enhanced glutaminolysis, reduced the level of unsaturated fatty acids, enhanced the β-oxidation of unsaturated fatty acids in the mitochondria, boosted the tricarboxylic acid (TCA) cycle, and accelerated thymic atrophy. Overall, these results imply that metabolic reprogramming is directly related to thymic remodeling.

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睾酮通过改变雄性大鼠的代谢重塑调节胸腺重塑

胸腺是一个能量消耗器官，其新陈代谢会随着萎缩而发生变化。睾酮可调节胸腺重塑（萎缩和再生）。然而，睾酮介导的胸腺萎缩和再生过程中能量代谢的特点仍不清楚。在这项研究中，我们证实了睾酮消减（通过免疫抑制和手术阉割实施）会诱发胸腺的整体代谢变化。京都基因与基因组百科全书》对不同代谢物的通路富集和对总代谢物的代谢物集富集分析表明，睾酮消融影响了胸腺的糖酵解、谷氨酸代谢和脂肪酸β氧化。睾酮消融诱导的胸腺再生伴随着糖酵解和谷氨酸代谢的减弱以及脂肪酸组成和含量的改变。在免疫阉割大鼠和手术阉割大鼠体内补充睾酮会增强谷氨酸酵解，降低不饱和脂肪酸的水平，增强线粒体中不饱和脂肪酸的β-氧化，促进三羧酸（TCA）循环，加速胸腺萎缩。总之，这些结果表明，代谢重编程与胸腺重塑直接相关。

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来源期刊

General and comparative endocrinology 医学-内分泌学与代谢

CiteScore

5.60

自引率

7.40%

发文量

120

审稿时长

2 months

期刊介绍： General and Comparative Endocrinology publishes articles concerned with the many complexities of vertebrate and invertebrate endocrine systems at the sub-molecular, molecular, cellular and organismal levels of analysis.