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Identification of Pyrvinium, an Anthelmintic Drug, as a Novel Anti-Adipogenic Compound Based on the Gene Expression Microarray and Connectivity Map

Obesity is a serious health problem, while the current anti-obesity drugs are not very effective. The Connectivity Map (C-Map), an in-silico drug screening approach based on gene expression profiles, has recently been indicated as a promising strategy for drug repositioning. In this study, we perfor...

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Detalles Bibliográficos
Autores principales: Wang, Zonggui, Dai, Zhong, Luo, Zhicong, Zuo, Changqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650900/
https://www.ncbi.nlm.nih.gov/pubmed/31261664
http://dx.doi.org/10.3390/molecules24132391
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author Wang, Zonggui
Dai, Zhong
Luo, Zhicong
Zuo, Changqing
author_facet Wang, Zonggui
Dai, Zhong
Luo, Zhicong
Zuo, Changqing
author_sort Wang, Zonggui
collection PubMed
description Obesity is a serious health problem, while the current anti-obesity drugs are not very effective. The Connectivity Map (C-Map), an in-silico drug screening approach based on gene expression profiles, has recently been indicated as a promising strategy for drug repositioning. In this study, we performed mRNA expression profile analysis using microarray technology and identified 435 differentially expressed genes (DEG) during adipogenesis in both C3H10T1/2 and 3T3-L1 cells. Then, DEG signature was uploaded into C-Map, and using pattern-matching methods we discovered that pyrvinium, a classical anthelminthic, is a novel anti-adipogenic differentiation agent. Pyrvinium suppressed adipogenic differentiation in a dose-dependent manner, as evidenced by Oil Red O staining and the mRNA levels of adipogenic markers. Furthermore, we identified that the inhibitory effect of pyrvinium was resulted primarily from the early stage of adipogenesis. Molecular studies showed that pyrvinium downregulated the expression of key transcription factors C/EBPa and PPARγ. The mRNA levels of notch target genes Hes1 and Hey1 were obviously reduced after pyrvinium treatment. Taken together, this study identified many differentially expressed genes involved in adipogenesis and demonstrated for the first time that pyrvinium is a novel anti-adipogenic compound for obesity therapy. Meanwhile, we provided a new strategy to explore potential anti-obesity drugs.
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spelling pubmed-66509002019-08-07 Identification of Pyrvinium, an Anthelmintic Drug, as a Novel Anti-Adipogenic Compound Based on the Gene Expression Microarray and Connectivity Map Wang, Zonggui Dai, Zhong Luo, Zhicong Zuo, Changqing Molecules Article Obesity is a serious health problem, while the current anti-obesity drugs are not very effective. The Connectivity Map (C-Map), an in-silico drug screening approach based on gene expression profiles, has recently been indicated as a promising strategy for drug repositioning. In this study, we performed mRNA expression profile analysis using microarray technology and identified 435 differentially expressed genes (DEG) during adipogenesis in both C3H10T1/2 and 3T3-L1 cells. Then, DEG signature was uploaded into C-Map, and using pattern-matching methods we discovered that pyrvinium, a classical anthelminthic, is a novel anti-adipogenic differentiation agent. Pyrvinium suppressed adipogenic differentiation in a dose-dependent manner, as evidenced by Oil Red O staining and the mRNA levels of adipogenic markers. Furthermore, we identified that the inhibitory effect of pyrvinium was resulted primarily from the early stage of adipogenesis. Molecular studies showed that pyrvinium downregulated the expression of key transcription factors C/EBPa and PPARγ. The mRNA levels of notch target genes Hes1 and Hey1 were obviously reduced after pyrvinium treatment. Taken together, this study identified many differentially expressed genes involved in adipogenesis and demonstrated for the first time that pyrvinium is a novel anti-adipogenic compound for obesity therapy. Meanwhile, we provided a new strategy to explore potential anti-obesity drugs. MDPI 2019-06-28 /pmc/articles/PMC6650900/ /pubmed/31261664 http://dx.doi.org/10.3390/molecules24132391 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Zonggui
Dai, Zhong
Luo, Zhicong
Zuo, Changqing
Identification of Pyrvinium, an Anthelmintic Drug, as a Novel Anti-Adipogenic Compound Based on the Gene Expression Microarray and Connectivity Map
title Identification of Pyrvinium, an Anthelmintic Drug, as a Novel Anti-Adipogenic Compound Based on the Gene Expression Microarray and Connectivity Map
title_full Identification of Pyrvinium, an Anthelmintic Drug, as a Novel Anti-Adipogenic Compound Based on the Gene Expression Microarray and Connectivity Map
title_fullStr Identification of Pyrvinium, an Anthelmintic Drug, as a Novel Anti-Adipogenic Compound Based on the Gene Expression Microarray and Connectivity Map
title_full_unstemmed Identification of Pyrvinium, an Anthelmintic Drug, as a Novel Anti-Adipogenic Compound Based on the Gene Expression Microarray and Connectivity Map
title_short Identification of Pyrvinium, an Anthelmintic Drug, as a Novel Anti-Adipogenic Compound Based on the Gene Expression Microarray and Connectivity Map
title_sort identification of pyrvinium, an anthelmintic drug, as a novel anti-adipogenic compound based on the gene expression microarray and connectivity map
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650900/
https://www.ncbi.nlm.nih.gov/pubmed/31261664
http://dx.doi.org/10.3390/molecules24132391
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