Establishment of a lipid metabolism disorder model in ApoEb mutant zebrafish

Elsevier

Available online 19 October 2022

AtherosclerosisHighlights•

ApoEb knockout supplemented with high-fat diet make a lipid metabolism disorder model in zebrafish.

Both simvastatin and ezetimibe significantly relieve intravascular lipid accumulation in the ApoEb deficient zebrafish model.

Xuezhikang may prevent atherosclerosis through both lipid-lowering effect and its inhibitory effect on inflammation.

AbstractBackground and aims

ApoEb is a zebrafish homologous to mammalian ApoE, whose deficiency would lead to lipid metabolism disorders (LMDs) like atherosclerosis. We attempted to knock out the zebrafish ApoEb, then establish a zebrafish model with LMD.

Methods

ApoEb was knocked out using the CRISPR/Cas9 system, and the accumulation of lipids was confirmed by Oil Red O staining, confocal imaging, and lipid measurements. The lipid-lowering effects of simvastatin (SIM), ezetimibe (EZE) and Xuezhikang (XZK), an extract derived from red yeast rice, were evaluated through in vivo imaging in zebrafish larvae.

Results

In the ApoEb mutant, significant vascular lipid deposition occurred, and lipid measurement performed in the whole-body homogenate of larvae and adult plasma showed significantly increased lipid levels. SIM, EZE and XZK apparently relieved hyperlipidemia in ApoEb mutants, and XZK had a significant inhibitory effect on the recruitment of neutrophils and macrophages.

Conclusions

In this study, an LMD model has been established in ApoEb mutant zebrafish. We suggest that this versatile model could be applied in studying hypercholesterolemia and related vascular pathology in the context of early atherosclerosis, as well as the physiological function of ApoE.

Keywords

Hyperlipidemia

Atherosclerosis

Apolipoprotein

ApoEb

Xuezhikang

Zebrafish

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