title: 1H NMR-based metabolic profiling reveals the effects of fluoxetine on lipid and amino acid metabolism in astrocytes.
abstract: Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), is a prescribed and effective antidepressant and generally used for the treatment of depression. Previous studies have revealed that the antidepressant mechanism of fluoxetine was related to astrocytes. However, the therapeutic mechanism underlying its mode of action in astrocytes remains largely unclear. In this study, primary astrocytes were exposed to 10 µM fluoxetine; 24 h post-treatment, a high-resolution proton nuclear magnetic resonance (1H NMR)-based metabolomic approach coupled with multivariate statistical analysis was used to characterize the metabolic variations of intracellular metabolites. The orthogonal partial least-squares discriminant analysis (OPLS-DA) score plots of the spectra demonstrated that the fluoxetine-treated astrocytes were significantly distinguished from the untreated controls. In total, 17 differential metabolites were identified to discriminate the two groups. These key metabolites were mainly involved in lipids, lipid metabolism-related molecules and amino acids. This is the ﬁrst study to indicate that fluoxetine may exert antidepressant action by regulating the astrocyte's lipid and amino acid metabolism. These findings should aid our understanding of the biological mechanisms underlying fluoxetine therapy.
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China. jasenbai@gmail.com.|Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China. jasenbai@gmail.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. jasenbai@gmail.com.|Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. jasenbai@gmail.com.
authors.forename: Shunjie
authors.initials: S
authors.lastname: Bai
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China. Veromcachou@gmail.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. Veromcachou@gmail.com.
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China. cpfzero@163.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. cpfzero@163.com.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China. yingyuf0311@163.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. yingyuf0311@163.com.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China. baisj888@126.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. baisj888@126.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing 400016, China. huang_wen@163.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China. yujialaowu2011@163.com.|Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China. yujialaowu2011@163.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. yujialaowu2011@163.com.|Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. yujialaowu2011@163.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China. shaoweihua0615@aliyun.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. shaoweihua0615@aliyun.com.
authors.forename: Weihua
authors.initials: W
authors.lastname: Shao
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China. lingyun155@126.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. lingyun155@126.com.
authors.forename: Xinfa
authors.initials: X
authors.lastname: Wang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China. liumeilinglinsa@sina.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. liumeilinglinsa@sina.com.
authors.forename: Meiling
authors.initials: M
authors.lastname: Liu
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China. duduzjj@163.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. duduzjj@163.com.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China. xiepeng@cqmu.edu.cn.|Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China. xiepeng@cqmu.edu.cn.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. xiepeng@cqmu.edu.cn.|Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. xiepeng@cqmu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D005473:Fluoxetine / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D055442:Metabolome; D066244:Proton Magnetic Resonance Spectroscopy; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors