Deciphering risperidone-induced lipogenesis by network pharmacology and molecular validation
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ABSTRACT:
PROVIDER: PRJNA813537 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18255645.fastq.gz | Fastqsanger.gz | |||
| SRR18255646_1.fastq.gz | Fastqsanger.gz | |||
| SRR18255646_2.fastq.gz | Fastqsanger.gz | |||
| SRR18255647.fastq.gz | Fastqsanger.gz | |||
| SRR18255648.fastq.gz | Fastqsanger.gz |
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Project description:Risperidone is an atypical antipsychotic that can cause substantial weight gain. The pharmacological targets and molecular mechanisms related to risperidone-induced lipogenesis (RIL) remain to be elucidated. Therefore, network pharmacology and further experimental validation were undertaken to explore the action mechanisms of RIL. In this study, RIL was systematically analyzed using integrating multiple databases through integrated network pharmacology, transcriptomics, molecular docking, and molecular experiment analysis. The potential signaling pathways for RIL were identified and experimentally validated using Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Our experimental data showed that Risperidone promotes adipocyte differentiate and lipid accumulation. And network pharmacology and GO analyses showed that risperidone induced adipocyte metabolism, differentiation, and lipid accumulation related functions. Intersecting analysis, molecular docking, and pathway validation analysis indicated that risperidone activated adipocytokine signaling pathway related genes by targeting MAPK14 (Mitogen-activated protein kinase 14), MAPK8 (Mitogen-activated protein kinase 8), and RXRA (Retinoic acid receptor RXR-alpha), thereby inhibiting long-chain fatty acid beta-oxidation by suppressing STAT3 (Signal transducer and activator of transcription 3) expression and phosphorylation. This study suggested that Risperidone increases adipocyte lipid accumulation by plausible inhibiting long-chain fatty acid beta-oxidation through targeting MAPK14, MAPK8, and RXRA.
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Project description:BackgroundRisperidone is an atypical antipsychotic that can cause substantial weight gain. The pharmacological targets and molecular mechanisms related to risperidone-induced lipogenesis (RIL) remain to be elucidated. Therefore, network pharmacology and further experimental validation were undertaken to explore the action mechanisms of RIL.MethodsRILs were systematically analyzed by integrating multiple databases through integrated network pharmacology, transcriptomics, molecular docking, and molecular experiment analysis. The potential signaling pathways for RIL were identified and experimentally validated using gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) analysis.ResultsRisperidone promotes adipocyte differentiation and lipid accumulation through Oil Red O staining and reverse transcription-polymerase chain reaction (RT-PCR). After network pharmacology and GO analysis, risperidone was found to influence cellular metabolism. In addition, risperidone influences adipocyte metabolism, differentiation, and lipid accumulation-related functions through transcriptome analysis. Intersecting analysis, molecular docking, and pathway validation analysis showed that risperidone influences the adipocytokine signaling pathway by targeting MAPK14 (mitogen-activated protein kinase 14), MAPK8 (mitogen-activated protein kinase 8), and RXRA (retinoic acid receptor RXR-alpha), thereby inhibiting long-chain fatty acid β-oxidation by decreasing STAT3 (signal transducer and activator of transcription 3) expression and phosphorylation.ConclusionRisperidone increases adipocyte lipid accumulation by plausibly inhibiting long-chain fatty acid β-oxidation through targeting MAPK14 and MAPK8.
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