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Pharmacopsychiatry 2021; 54(03): 131-141
DOI: 10.1055/a-1351-0566
Original Paper

Metformin Attenuates the Metabolic Disturbance and Depression-like Behaviors Induced by Corticosterone and Mediates the Glucose Metabolism Pathway

Yong Hao   *
1   Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
,
Yingpeng Tong   *
2   Institute of Natural Medicine and Health Product, School of Advanced Study, Taizhou University, Taizhou, China
,
Yanhong Guo
3   Qingdao Mental Health Center, Qingdao University, Qingdao, China
,
Xiaoe Lang
4   Department of Psychiatry, The First Clinical Medical College, Shanxi Medical University, Taiyuan, China
,
Xinxin Huang
5   Shanghai Mental Health Center, Shanghai, China
,
Xiaoxian Xie
6   College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China
,
Yangtai Guan   #
1   Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
,
Zezhi Li   #
1   Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
› Author Affiliations Funding: This work was supported by Shanghai Jiao Tong University Medical Engineering Foundation (YG2015MS52, YG2016MS48), Shanghai Jiao Tong University School of Medicine (19XJ11006). We declare that the funding has no influence on the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
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Abstract

Background Metabolism disturbances are common in patients with depression. The drug metformin has been reported to exhibit antidepressant activity. The purpose of this study was to investigate metabolism disturbances induced by corticosterone (CORT) and determine if metformin can reverse these effects and their accompanying depression-like behaviors.

Methods Rats were exposed to corticosterone with or without metformin administration. Depression-like behaviors were tested. Gene expression was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. In addition, the metabolites were quantified by LC-MS/MS analysis.

Results Metformin attenuated the depression-like behaviors induced by CORT. Furthermore, metformin reversed disturbances in body weight, serum glucose, and triglyceride levels, as well as hepatic TG levels induced by CORT. Metformin normalized the alterations in the expression of glucose metabolism-related genes (PGC-1α, G6pc, Pepck, Gck, PYGL, Gys2, PKLR, GLUT4) and insulin resistance-related genes (AdipoR1, AdipoR2) in the muscles and livers of rats induced by CORT. Metabolomic analysis showed that metformin reversed the effects of CORT on 11 metabolites involved in the pathways of the tricarboxylic acid cycle, glycolysis, and gluconeogenesis (3-phospho-D-glycerate, β-D-fructose 6-phosphate, D-glucose 6-phosphate, and pyruvate).

Conclusion Our findings suggest that metformin can attenuate metabolism disturbances and depression-like behaviors induced by CORT mediating the glucose metabolism pathway.

Key words

metformin - glucose metabolism - LC-MS/MS - depression-like behavior - metabolomics analysis

* Yong Hao and Yingpeng Tong contributed equally to this work.


# Zezhi Li and Yangtai Guan are both corresponding authors.


Supplementary Material



Publication History

Received: 28 September 2020
Received: 11 December 2020

Accepted: 29 December 2020

Article published online:
25 February 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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