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PMID: 39656235 Published · ppublish English Journal Article

Biological mechanism and functional verification of key genes related to major depressive disorder and type 2 diabetes mellitus.

Mammalian genome : official journal of the International Mammalian Genome Society ·Vol. 36 ·No. 1 ·2025-03-00 ·Pages 66-82

Fang T, Shen N, Shi Z, Luo W, Di Y, Liu X, Ma S, Wang J, Hou S

Abstract

Major depressive disorder (MDD) and type 2 diabetes (T2D) have been shown to be linked, but a comprehensive understanding of the underlying molecular mechanisms remains elusive. The purpose of this study was to explore the biological relationship between MDD and T2D and verify the functional roles of key genes. We used the Gene Expression Omnibus database to investigate the targets associated with MDD and T2D. Using linear models for microarray data, differentially expressed genes associated with MDD and T2D were identified in GSE76826 and GSE95849, respectively, and 126 shared genes were significantly upregulated. Weighted gene coexpression network analysis identified modules associated with MDD and T2D in the GSE38206 and GSE20966 datasets and identified 8 common genes. Functional enrichment analysis revealed that these genes were enriched in cell signaling, enzyme activity, cell structure and amino acid biosynthesis and involved in cell death pathways. Finally, combined with the CTD and GeneCards databases, lysophosphatidylglycerol acyltransferase 1 (LPGAT1) was identified as a key gene. LPGAT1 was validated in GSE201332 and GSE182117, and the subject operating characteristic curve showed good diagnostic potential for MDD and T2D. Additionally, we used an in vitro model of MDD related to T2D to verify the expression of LPGAT1. A subsequent gene knockdown assay revealed that the downregulation of LPGAT1 improved mitochondrial function and reduced apoptosis in damaged neurons. Taken together, our results highlight the role of LPGAT1 in the connection between MDD and T2D, and these findings provide new insights into potential therapeutic targets for depression associated with diabetes.

Keywords
Bioinformatics analysis Hub gene Major depressive disorder Type 2 diabetes Verification of functionality
MeSH Terms
Diabetes Mellitus, Type 2/genetics Humans Major Depressive Disorder/genetics Gene Regulatory Networks Gene Expression Profiling Databases, Genetic Gene Expression Regulation
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Fang Tao
Tianjin Fourth Central Hospital, Tianjin University, Tianjin, 300072, China. | Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin, 300072, China.
Shen Na
Tianjin Fourth Central Hospital, Tianjin University, Tianjin, 300072, China.
Shi Zhemin
Department of Histology and Embryology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease of Ministry of Education, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
Luo Weishun
Pharmacy Department, Tianjin Fourth Central Hospital, Tianjin, 300140, China.
Di Yanbo
Tianjin Fourth Central Hospital, Tianjin University, Tianjin, 300072, China.
Liu Xuan
Pharmaceutical Clinical Trial Institution Office, Tianjin Fourth Central Hospital, Tianjin, 300140, China.
Ma Shengnan
Pharmacy Department, Tianjin Fourth Central Hospital, Tianjin, 300140, China.
Wang Jing
Department of Medicine, Tianjin Medical College, Tianjin, 300222, China. [email protected].
Hou Shike
Tianjin Fourth Central Hospital, Tianjin University, Tianjin, 300072, China. [email protected]. | Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin, 300072, China. [email protected].
Conflict of Interest

Declarations. Competing interests: The authors declare no competing interests.

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Article Info
Journal
Mammalian genome : official journal of the International Mammalian Genome Society
Abbr.
Mamm Genome
ISSN
1432-1777
DOI
10.1007/s00335-024-10090-z
Email
[email protected]
[email protected]
Published
2025-03-00
Epub
2024-00-10
Pages
66-82
Language
English
Region
United States
NLM ID
9100916
Subset
IM
Grants
Tianjin Municipal Health Commission · 2021190
Tianjin Municipal Health Commission · TJWJ2021QN055
Exceptional Young Talents Fostering Foundation of the Tianjin 4th Central Hospital · tjdszxyy20220021
External Links
PubMed source DOI: 10.1007/s00335-024-10090-z View journal details
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