| Summary: | <i>Citrus aurantium</i> L. dry extracts (<i>CA</i>de) improve adipogenesis in vitro. These effects are dependent from an early modulation of CCAAT/enhancer-binding protein beta (<i>C/Ebpβ</i>) expression and cyclic Adenosine Monophosphate (cAMP) response element-binding protein (<i>CREB</i>) activation. <i>C/Ebpβ</i> and <i>Creb</i> are also targets of <i>miR-155</i>. This study investigated whether <i>CA</i>de regulates <i>miR-155</i> expression in the early stages of adipogenesis and whether it ameliorates adipocyte differentiation of cells exposed to tumor necrosis factor-alpha (TNFα). Adipogenic stimuli (AS) were performed in 3T3-L1 pre-adipocytes treated with <i>CA</i>de, TNFα, or both. Gene and miRNA expression were determined by quantitative real-time PCR. Adipogenesis was evaluated by Oil-Red O staining. <i>CA</i>de treatment enhanced AS effects during the early adipogenesis phases by further down-regulating <i>miR-155</i> expression and increasing both <i>C/Ebpβ</i> and <i>Creb</i> mRNA and protein levels. At variance, TNFα inhibited 3T3-L1 adipogenesis and abolished AS effects on <i>miR-155</i>, <i>C/Ebpβ</i>, and <i>Creb</i> expression. However, in cells exposed to TNFα, <i>CA</i>de improved adipocyte differentiation and restored the AS effects on miRNA and gene expression at early time points. In conclusion, this study identified <i>miR-155</i> down-regulation as part of the mechanism through which <i>CA</i>de enhances adipogenesis of pre-adipocytes in vitro. Furthermore, it provides evidence of <i>CA</i>de efficacy against TNFα negative effects on adipogenesis.
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