Indole-3-carbinol inhibits lipid deposition and promotes autophagy in hyperlipidemia zebrafish larvae

Indole-3-carbinol (I3C) is extracted from cruciferous vegetables and is well known for its anti-cancer, antioxidant and anti-inflammatory effects. This study investigated the protective effect of I3C in hyperlipidemia zebrafish larvae and early life stage toxicity of I3C on zebrafish embryos/larvae. Zebrafish larvae were fed with 4% high-cholesterol diet (HCD) and treated with I3C 2.5μmol/L and 5μmol/L for two weeks. Confocal image analysis, oil Red O staining were used to analysis vascular lipid accumulation and western blotting was used to evaluate possible mechanics. In addition, zebrafish embryos were treated with I3C for 96 h to assess the general toxicity and cardiotoxicity. We found that lipid deposition on vasculature was dose-dependently decreased in the I3C treated groups as compared with control group (47%, 23%, p<0.01). Moreover, we demonstrated that I3C inhibited lipid deposition by inducing autophagy, as identified by the enhancement of LC3-II, beclin-1, hVps34 and m-cathepsin D as well as by the reduction of P62, Bcl-2, Akt, p- Akt, mTOR, and p- mTOR in HCD fed zebrafish larvae (p<0.05). In summary, I3C shows protective effects on hyperlipidemia zebrafish larvae and maybe a promising multitarget drug in the prevention and protection against atherosclerotic.