Miyares Rosa L, de Rezende Vitor B, Farber Steven A
Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA. Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Mental Health, School of Medicine of Federal University of Minas Gerais, 30130-100 Belo Horizonte, Brazil.
Dis Model Mech. 2014 Jul;7(7):915-27. doi: 10.1242/dmm.015800. Epub 2014 May 8.
Dyslipidemias are a major cause of morbidity and mortality in the world, particularly in developed nations. Investigating lipid and lipoprotein metabolism in experimentally tractable animal models is a crucial step towards understanding and treating human dyslipidemias. The zebrafish, a well-established embryological model, is emerging as a notable system for studies of lipid metabolism. Here, we describe the value of the lecithotrophic, or yolk-metabolizing, stages of the zebrafish as a model for studying lipid metabolism and lipoprotein transport. We demonstrate methods to assay yolk lipid metabolism in embryonic and larval zebrafish. Injection of labeled fatty acids into the zebrafish yolk promotes efficient uptake into the circulation and rapid metabolism. Using a genetic model for abetalipoproteinemia, we show that the uptake of labeled fatty acids into the circulation is dependent on lipoprotein production. Furthermore, we examine the metabolic fate of exogenously delivered fatty acids by assaying their incorporation into complex lipids. Moreover, we demonstrate that this technique is amenable to genetic and pharmacologic studies.
血脂异常是全球发病和死亡的主要原因，在发达国家尤为如此。在易于实验操作的动物模型中研究脂质和脂蛋白代谢是理解和治疗人类血脂异常的关键一步。斑马鱼是一种成熟的胚胎学模型，正成为脂质代谢研究的一个重要系统。在此，我们描述了斑马鱼的卵黄营养阶段或卵黄代谢阶段作为研究脂质代谢和脂蛋白转运模型的价值。我们展示了在胚胎和幼体斑马鱼中检测卵黄脂质代谢的方法。将标记脂肪酸注射到斑马鱼卵黄中可促进其有效摄取到循环系统并快速代谢。利用无β脂蛋白血症的遗传模型，我们表明标记脂肪酸摄取到循环系统中依赖于脂蛋白的产生。此外，我们通过检测外源递送脂肪酸掺入复合脂质的情况来研究其代谢命运。而且，我们证明了该技术适用于遗传和药理学研究。
