Zebrafish models of dyslipidemia: relevance to atherosclerosis and angiogenesis

Abstract

Lipid and lipoprotein metabolism in zebrafish and in humans are remarkably similar. Zebrafish express all major nuclear receptors, lipid transporters, apolipoproteins and enzymes involved in lipoprotein metabolism. Unlike mice, zebrafish express cetp and the Cetp activity is detected in zebrafish plasma. Feeding zebrafish a high cholesterol diet, without any genetic intervention, results in significant hypercholesterolemia and robust lipoprotein oxidation, making zebrafish an attractive animal model to study mechanisms relevant to early development of human atherosclerosis. These studies are facilitated by the optical transparency of zebrafish larvae and the availability of transgenic zebrafish expressing fluorescent proteins in endothelial cells and macrophages. Thus, vascular processes can be monitored in live animals. In this review article we discuss recent advances in using dyslipidemic zebrafish in atherosclerosis-related studies. We also summarize recent work connecting lipid metabolism with regulation of angiogenesis, the work that considerably benefited from using the zebrafish model. These studies uncovered the role of aibp, abca1, abcg1, mtp, apoB and apoC2 in regulation of angiogenesis in zebrafish and paved the way for future studies in mammals, which may suggest new therapeutic approaches to modulation of excessive or diminished angiogenesis contributing to the pathogenesis of human disease.

Expression and function of ATP-dependent potassium channels in zebrafish islet β-cells

“…Larvae are transparent, allowing easy visualization of genetic markers or fluorescent dyes [14,45]. Zebrafish develop metabolic abnormalities when fed high-fat diets [46,47], show similar complications of persistently high glucose and have many of the same transcription factor pathways involved in development of endocrine, liver and other organs important in controlling metabolism [44,48]. While zebrafish may thus offer major advantages for screening diabetes modifiers, details of comparative organ biology must first be evaluated and further studies like those we describe here are required.…”

Deficient Cholesterol Esterification in Plasma of apoc2 Knockout Zebrafish and Familial Chylomicronemia Patients

“…The genes involved in lipid and lipoprotein metabolism, such as APOC2 , LPL , LCAT and CETP , are conserved from zebrafish to humans [21–24]. In our previous study, we have developed an apoc2 knockout zebrafish model, which replicates many aspects of human FCS, including a pronounced hypertriglyceridemia, associated with an increase in chylomicrons and VLDL, and decreased LDL and HDL [25].…”

Rhamnan sulphate from Monostroma nitidum attenuates hepatic steatosis by suppressing lipogenesis in a diet-induced obesity zebrafish model

“…Over the last decade, the zebrafish (Danio rerio) model has been increasingly employed in investigating human obesity and obesity-related diseases, including hepatic steatosis, diabetes, non-alcoholic steatohepatitis and atherosclerosis (Seth, Stemple, & Barroso, 2013). In zebrafish, lipid metabolism is very similar to that in humans in terms of lipid synthesis and fatty acid oxidation (Fang, Liu, & Miller, 2014;Holtta-Vuori et al, 2010). Recent studies have begun to explore zebrafish homologues of mammalian genes involved in lipid metabolism.…”