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
作者： Zhang, Meng-ling 1 ; Li, Xiao-peng 3 ; Gao, Li-fang 1 ; Liu, Jian 3 ; Bi, Zi-jun 1 ; Miao, Yu-han 1 ; Shan, Yang 3 ; Yu, Huan-ling 1 ;
作者机构： 1.Capital Med Univ, Sch Publ Hlth, Beijing Key Lab Environm Toxicol, Beijing 100069, Peoples R China
2.Chinese Acad Inspect & Quarantine, Inst Chem Safety, Beijing 100176, Peoples R China
3.Hunan Acad Agr Sci, Hunan Agr Prod Proc Inst, Hunan Prov Key Lab Fruits & Vegetables Storage Pro, Changsha 410000, Peoples R China
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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