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Series GSE242103 Query DataSets for GSE242103
Status Public on Apr 24, 2024
Title Cationic amphiphilic drug induced phospholipidosis and lysosomal dysgenesis during in vitro adipogenesis
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Selective Serotonin Reuptake Inhibitors (SSRIs) are widely used medications for the treatment of major depressive disorder. However, long-term SSRI use has been associated with weight gain and altered lipid profiles. These findings suggest that SSRIs may have negative effects on metabolism. Exposure to certain chemicals called 'obesogens' are known to promote lipid accumulation and obesity by modulating adipogenesis. Here, we investigated whether citalopram (CIT) and sertraline (SER) interfere with the process of adipogenesis, using human mesenchymal stem cells (MSCs) in a 2D and a 3D model. Assessment of intracellular lipid accumulation by fluorescence staining was used as a measure for enhanced adipogenesis. To explore possible mechanisms behind SSRIs' effects, receptor mediated activity was studied using responsive cell lines for various nuclear receptors. Furthermore, RNA sequencing was performed in the 3D model, followed by differential gene expression and pathway analysis. A dose dependent increase in lipid accumulation was observed in both models with CIT and SER. For the 3D model, the effect was seen in a range close to reported steady-state plasma concentrations (0,065-0,65 μM for SER and 0,12-0,92 μM for CIT). Pathway analysis revealed unexpected results of downregulation in adipogenesis-related pathways and upregulation in phospholipids and lysosomal pathways. This was confirmed by an observed increase in lysosomes in the 2D model. Our findings suggest lysosomal dysfunction and disrupted lipid metabolism in mature adipocytes, leading to excessive phospholipid synthesis. Moreover, important adipogenic processes are inhibited, potentially leading to dysfunctional adipocytes, which might have implications in maintenance of a healthy metabolic balance.
 
Overall design For transcriptomics profiling, cells were differentiated in parallel via 2D or 3D protocols, with and without the positive control ROSI at 0.1 µM, CIT or SER where 0.1% DMSO was used as a vehicle control. These exposures were repeated in 3 independent biological experiments.
Web link http://10.1016/j.taap.2024.116937
 
Contributor(s) Bozdag D, Orhan HG, van Voorthuizen J, Kamstra JH, Lentz S
Citation(s) 38643950
Submission date Aug 31, 2023
Last update date Apr 24, 2024
Contact name Jorke Kamstra
E-mail(s) j.h.kamstra@uu.nl
Organization name Utrecht University
Department Faculty of Veterinary Medicine
Lab IRAS-TOX
Street address PO Box 80177
City Utrecht
State/province Non United States Or Canada
ZIP/Postal code 3508 TD
Country Netherlands
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (25)
GSM7749041 2D_Control1
GSM7749042 2D_Control2
GSM7749043 2D_Control3
Relations
BioProject PRJNA1011331

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE242103_Seqdata_2D_3D.xlsx 9.6 Mb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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