Nobiletin, an activator of the pyruvate kinase isozyme M1/M2 protein, upregulated the glycolytic signalling pathway and alleviated depressive-like behaviour caused by artificial light exposure at night in zebrafish

文献类型： 外文期刊

第一作者： Zhang, Meng-ling

作者： Zhang, Meng-ling;Gao, Li-fang;Bi, Zi-jun;Miao, Yu-han;Yu, Huan-ling;Zhang, Meng-ling;Li, Xiao-peng;Liu, Jian;Shan, Yang

作者机构：

关键词： Nobiletin; Artificial light at night; Zebrafish; Depressive-like behaviour; Circadian rhythm; Glycolysis

期刊名称：FOOD CHEMISTRY （ 影响因子：9.8； 五年影响因子：9.7 ）

ISSN： 0308-8146

年卷期： 2025 年 463 卷

页码：

收录情况： SCI

摘要： We established a zebrafish model of depression-like behaviour induced by exposure to artificial light at night (ALAN) and found that nobiletin (NOB) alleviated depression-like behaviour. Subsequently, based on the results of a 24-h free movement assay, clock gene expression and brain tissue transcriptome sequencing, the glycolysis signalling pathway was identified as a potential target through which NOB exerted antidepressant effects. Using the ALAN zebrafish model, we found that supplementation with exogenous L-lactic acid alleviated depressivelike behaviour. Molecular docking and molecular dynamics simulations revealed an inter-molecular interaction between NOB and the pyruvate kinase isozyme M1/M2 (PKM2) protein. We then used compound 3 k to construct a zebrafish model in which PKM2 was inhibited. Our analysis of this model suggested that NOB alleviated depression-like behaviour via inhibition of PKM2. In summary, NOB alleviated depressive-like behaviour induced by ALAN in zebrafish via targeting of PKM2 and activation of the glycolytic signalling pathway.

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