title: Zebrafish yolk lipid processing: a tractable tool for the study of vertebrate lipid transport and metabolism.
abstract: 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.
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA. Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Rosa L
authors.initials: RL
authors.lastname: Miyares
authors.affiliation: Department of Mental Health, School of Medicine of Federal University of Minas Gerais, 30130-100 Belo Horizonte, Brazil.
authors.forename: Vitor B
authors.initials: VB
authors.lastname: de Rezende
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA. farber@ciwemb.edu.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Farber
mesh_terms: D065567:Absorption, Physiological / Q000187:drug effects; D000818:Animals; D001681:Biological Assay / Q000379:methods*; D001692:Biological Transport / Q000187:drug effects; D001896:Boron Compounds / Q000378:metabolism; D004530:Egg Yolk / Q000187:drug effects / Q000378:metabolism*; D047108:Embryonic Development / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism; D015203:Reproducibility of Results; D013194:Staining and Labeling; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D008077:Lipoproteins, LDL; D029961:Zebrafish Proteins
keywords: Dyslipidemia; Lecithotrophic; Lipoprotein; Placenta; Yolk sac; Yolk syncytial layer