Obesity is a serious health problem, while the current anti-obesity drugs are not very\neffective. The Connectivity Map (C-Map), an in-silico drug screening approach based on gene\nexpression profiles, has recently been indicated as a promising strategy for drug repositioning. In this\nstudy, we performed mRNA expression profile analysis using microarray technology and identified\n435 differentially expressed genes (DEG) during adipogenesis in both C3H10T1/2 and 3T3-L1 cells.\nThen, DEG signature was uploaded into C-Map, and using pattern-matching methods we discovered\nthat pyrvinium, a classical anthelminthic, is a novel anti-adipogenic differentiation agent. Pyrvinium\nsuppressed adipogenic differentiation in a dose-dependent manner, as evidenced by Oil Red O\nstaining and the mRNA levels of adipogenic markers. Furthermore, we identified that the inhibitory\neffect of pyrvinium was resulted primarily from the early stage of adipogenesis. Molecular studies\nshowed that pyrvinium downregulated the expression of key transcription factors C/EBPa and PPAR.\nThe mRNA levels of notch target genes Hes1 and Hey1 were obviously reduced after pyrvinium\ntreatment. Taken together, this study identified many differentially expressed genes involved in\nadipogenesis and demonstrated for the first time that pyrvinium is a novel anti-adipogenic compound\nfor obesity therapy. Meanwhile, we provided a new strategy to explore potential anti-obesity drugs.
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