Zebrafish yolk lipid processing: a tractable tool for the study of vertebrate lipid transport and metabolism

• Published in: Disease models & mechanisms 2014-07, Vol.7 (7), p.915-927
• Main Authors: Miyares, Rosa L, de Rezende, Vitor B, Farber, Steven A
• Format: Article
• Language: English
• Subjects: Abetalipoproteinemia; Absorption, Physiological - drug effects; Animal models; Animals; Biological Assay - methods; Biological Transport - drug effects; Biology; Boron Compounds - metabolism; Cardiovascular disease; Cholesterol; Danio rerio; Dyslipidemia; Egg Yolk - drug effects; Egg Yolk - metabolism; Embryonic Development - drug effects; Embryos; Enzyme Inhibitors - pharmacology; Enzymes; Fatty acids; Fatty Acids - metabolism; Genes; Genetic engineering; High density lipoprotein; Humans; Larva - drug effects; Larva - metabolism; Lecithotrophic; Lipid metabolism; Lipid Metabolism - drug effects; Lipids; Lipoprotein; Lipoproteins; Lipoproteins, LDL - metabolism; Liver; Metabolic disorders; Metabolism; Metabolites; Morbidity; Physiology; Placenta; Proteins; Reproducibility of Results; Resource; Staining and Labeling; Time Factors; Vertebrates; Yolk; Yolk sac; Yolk syncytial layer; Zebrafish; Zebrafish - embryology; Zebrafish - metabolism; Zebrafish Proteins - metabolism
• ISSN: 1754-8403; 1754-8411
• DOI: 10.1242/dmm.015800

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.