Whole-brain Transcriptomic Analysis of Weight Gain Mice induced by Olanzapine
10.12300/j.issn.1674-5817.2023.006
- VernacularTitle:奥氮平诱导体重增加小鼠的全脑转录组学分析
- Author:
Yuan ZHANG
1
;
Han LI
2
;
Chengfang ZHANG
1
Author Information
1. Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai 200124, China
2. Shanghai Mental Health Center, Shanghai Jiao Tong University of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai 201108, China
- Publication Type:Journal Article
- Keywords:
Olanzapine;
Body weight gain;
Whole brain;
RNA-Seq;
Mice
- From:
Laboratory Animal and Comparative Medicine
2023;43(3):262-270
- CountryChina
- Language:Chinese
-
Abstract:
Objective The transcriptome sequencing results of brain tissues of olanzapine-treated mice were analyzed to screen out differentially-expressed genes and explore potential targets of atypical antipsychotics leading to body weight gain.Methods Twenty female C57BL/6 mice were randomly divided into control group (Ctrl) and Olanzapine administration group (Olz), which were given saline and Olanzapine solution by gavage, respectively. The whole brain tissues were collected 8 weeks later for Transcriptome sequencing (RNA-Seq). The possible targets of olanzapine-induced body weight gain were identified by the Gene Ontology (GO) functional annotation analysis, the Kyoto Encyclopedia of Genes and Gnomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis. Differential expression levels of mRNAs were further verified by real-time quantitative fluorescence PCR (RT-qPCR).Results Compared with Ctrl group, 591 differentially expressed genes were screened in Olz group, including 251 up-regulated genes and 340 down-regulated genes. GO analysis showed that differential genes were widely involved in transcriptional process, among which the expression of genes related to the regulation of digestive system and cold-induced thermogenesis were significantly enriched. KEGG analysis showed that differential genes were widely involved in the interaction between neuroactive ligands and receptors, and the differential genes were significantly enriched in oxytocin signaling, fat digestion and absorption, and cholesterol metabolism pathways. RT-qPCR were performed to verify the expression levels of genes enriched in feeding regulation, gastric kinesis, thermogenesis, fat metabolism and other processes (Oxt, Trpv1, Adipoq, Phox2b, Abcg5, Mogat2, Dbh, Plac8 and Neurog1) as well as hub genes in PPI network (Fos, Dusp1 and Egr2), and the results were consistent with the trend of RNA-Seq.Conclusion Olanzapine administration resulted in changes in central feeding regulation, gastrointestinal motility, thermogenesis and other physiological processes in mice, which might be involved in body weight gain induced by olanzapine.
