Indole-3-carbinol, a vegetable phytochemical, inhibits adipogenesis by regulating cell cycle and AMPKα signaling

• I3C inhibits adipogenesis by regulating early adipogenic factors.
• I3C inhibits mitotic clonal expansion by regulating cell cycle.
• I3C deactivates phosphoinositide-3 kinase/serine threonine-specific kinase signaling.
• I3C activates 5′adenosine monophosphate-activated protein kinase α signaling.
• I3C inhibits lipid accumulation in zebrafish.

Indole-3-carbinol (I3C) is a phytochemical present mainly in cruciferous vegetables. In this study, we investigated the mechanism by which I3C blocks adipogenesis in 3T3-L1 cells, and evaluated the anti-adipogenic effect of I3C in zebrafish. Our data showed that I3C mainly inhibits early differentiation of adipocyte through cell cycle arrest. Inhibition of early differentiation was reflected by down-regulation of early adipogenic factors such as CCAAT-enhancer binding proteins β and δ (C/EBPβ and C/EBPδ), followed by down-regulation of late adipogenic factors such as peroxisome proliferator-activated receptor γ (PPARγ) and C/EBPα, and regulation of signaling molecules. This result was supported by a reduction in triglyceride (TG) levels and TG synthetic enzymes. I3C activated AMP-activated protein kinase α (AMPKα) to inhibit fatty acid synthesis. In addition, an anti-adipogenic effect of I3C was found in zebrafish study. Our data suggest that vegetables-derived I3C could reduce lipid accumulation via various molecular mechanisms in cell.