Project description:Given that celastrol?s leptin-sensitizing effect requires both high levels of circulating leptin and intact leptin receptor signaling, we analyzed the effect of celastrol on hypothalamic gene expression profile of db/db mice, which have high circulating levels of leptin, but lack intact leptin receptor signaling. This analysis will be serving as negative control for DIO mice analysis.
Project description:Since leptin signaling in the hypothalamus is critical to regulate food intake and body weight, we investigated how celastrol alters the hypothalamic transcriptome of DIO mice. By doing this analysis, genes with potential relevance for celastrol-mediated leptin sensitization could be identified.
Project description:Given that celastrol?s leptin-sensitizing effect requires high levels of circulating leptin, but lean mice have low levels of circulating leptin so that celastrol has no effect on lean mice. Analysis celastrol-induced hypothalamic gene expression profile change in lean mice will also be serving as negative control for DIO mice analysis.
Project description:Purpose: The goals of this study was to (1) evaluate the protective effect of celastrol on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis and (2) which genes were recovered by celastrol. Methods:To investigate the protective effect of celastrol on ANIT-induced cholestasis, the WT mice were randomly assigned into two groups, respectively (n=3): (1) ANIT; (2) ANIT+Celastrol. ANIT+Celastrol group was orally treated with celastrol (10 mg/kg dissolved in 1% DMSO + 2% Tween 80 + 97% water) for 5 consecutive days. After celastrol was treated for 3 days, ANIT and ANIT+Celastrol groups were given a single oral dose of ANIT. All mice were killed 48 h after ANIT administration. Liver samples were harvested and frozen at -80 °C before analysis. Results: A total of 978 DEGs were identified. Large numbers of these DEGs were related to activation of SIRT1, which included increased FXR signaling and inhibition of PPARγ, nuclear factor-kappa B (NF-κB), and P53 signaling. Conclusions: Celastrol could protect ANIT-induced cholestasis by recovering disrupted Sirt1 level.
Project description:To investigate effects of Adjudin on gene expression of islets from db/db mouse, islets from 12 to 13 weeks old male db/db mice were isolated, cultured in incubator for overnight recovery, and treated with either DMSO or 10 µM Adjudin for 1 day before RNA sequencing.