Lipid ingestion and metabolism. Lipids from foods are digested in GI tract. Ingested lipids are hydrolyzed into small, absorbable molecules such as fatty acids and monoglycerides and products by lipolysis are subsequently re-esterified into TGs in the enterocytes. Cholesterol is absorbed through the transport protein npc1l1, a critical mediator of cholesterol absorption. TGs with cholesterol, fat-soluble vitamins, cholesteryl ester and phospholipids forms chylomicrons in the intestine. Chylomicron acquires apolipoproteins from HDLs in vasculature. VLDLs are synthesized in liver, and they possess apoB-100, in contrast, chylomicrons possess apoB-48, although both deliver TGs to peripheral tissue. LDLs, converted particles from IDLs, are cleared in liver via LDL receptors. CETP mediates exchange of cholesteryl ester and TGs between VLDLs, LDLs and HDLs. GI, gastrointestinal; TG, triglyceride; HDL, high-density lipoprotein; VLDL, very low-density lipoprotein; apo, apolipoprotein; LDL, low-density lipoprotein; IDL, intermediate density lipoprotein; CETP, cholesteryl ester transfer protein.

Zebrafish hyperlipidemia model. As shown in humans, dyslipidemia in zebrafish is similarly induced by either environmental or genetic factors. Environmental factors such as continuous light exposure, chemical treatment, and diet regimens can influence lipid metabolism and predispose to dyslipidemia in zebrafish. In addition, abrogation of genes associated with lipid metabolism such as nr1h3 and apoc2 using genome editing tools or morpholino results in dysregulated lipid metabolism, leading to fatty liver, obesity and lipid accumulation in vasculature and other organs. HID, high-iron diet; HFD, high-fat diet; HCD, high-cholesterol diet.

High-throughput drug screen using zebrafish hyperlipidemia models. A pair of zebrafish provides hundreds of eggs per week, which enables production of genetically identical individuals for high throughput screen. In addition, zebrafish larvae are small enough to be raised in a small volume of aqueous media within a single well of multi-well plate, which increases the efficacy and reproducibility of the high throughput screen. Efficacy of candidates can be verified by lipid staining such as Oil Red O, Nile Red and BODIPY staining. Combined with phenotypic resemblance between hyperlipidemic zebrafish and humans, these aforementioned attributes as a model organism have propelled zebrafish as an important alternative model to investigate pathophysiology of dyslipidemia in humans.

Acknowledgments
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