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• W4292533813 abstract "Meroterpenoid furanasperterpene A (T2-3) with a novel 6/6/6/6/5 pentacyclic skeleton was isolated from the Aspergillus terreus GZU-31-1. Previously, we showed that T2-3 possessed significant lipid-lowering effects in 3T3-L1 adipocytes at 5 μM concentration. However, its therapeutic effect in metabolic disease and the underlying mechanisms of action remain unclear.High fat diet-induced obesity (DIO) mouse model and 3T3-L1 cell model were used to assess the anti-obesity effects of T2-3. Lipids in the adipocytes were examined by Oil Red O staining. β-catenin expression was examined by immunofluorescence and Western blotting, its activity was assessed by TOPflash/FOPflash assay.T2-3 possessed potent anti-obesity effects in DIO mice, it significantly reduced body weight and subcutaneous adipose tissue (SAT) mass. Mechanistic studies showed that T2-3 significantly inhibited 3T3-L1 preadipocyte differentiation as indicated by the reduced number of mature adipocytes. The treatments also reduced the expressions of critical adipogenic transcription factors CEBP-α and PPAR-γ in both 3T3-L1 adipocytes and SAT in DIO mice. Interestingly, T2-3 increased the cytoplasmic and nuclear expressions of β-catenin and the transcriptional activity of β-catenin in 3T3-L1 adipocytes; the elevated β-catenin expression was also observed in SAT of the T2-3-treated DIO mice. Indeed, upregulation of β-catenin activity suppressed adipogenesis, while β-catenin inhibitor JW67 reversed the anti-adipogenic effect of T2-3. Taken together, our data suggest that T2-3 inhibits adipogenesis by upregulating β-catenin activity.Our study is the first report demonstrating meroterpenoid furanasperterpene A as a novel 6/6/6/6/5 pentacyclic skeleton (T2-3) that possesses potent anti-adipogenic effect by targeting β-catenin signaling pathway. Our findings drive new anti-obesity drug discovery and provide drug leads for chemists and pharmacologists." @default.
• W4292533813 created "2022-08-22" @default.
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• W4292533813 date "2022-11-01" @default.
• W4292533813 modified "2023-10-06" @default.
• W4292533813 title "Discovery of a novel anti-obesity meroterpenoid agent targeted subcutaneous adipose tissue" @default.
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• W4292533813 doi "https://doi.org/10.1016/j.phymed.2022.154396" @default.
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