title: Zebrafish as a model for apolipoprotein biology: comprehensive expression analysis and a role for ApoA-IV in regulating food intake.
abstract: Improved understanding of lipoproteins, particles that transport lipids throughout the circulation, is vital to developing new treatments for the dyslipidemias associated with metabolic syndrome. Apolipoproteins are a key component of lipoproteins. Apolipoproteins are proteins that structure lipoproteins and regulate lipid metabolism through control of cellular lipid exchange. Constraints of cell culture and mouse models mean that there is a need for a complementary model that can replicate the complex in vivo milieu that regulates apolipoprotein and lipoprotein biology. Here, we further establish the utility of the genetically tractable and optically clear larval zebrafish as a model of apolipoprotein biology. Gene ancestry analyses were implemented to determine the closest human orthologs of the zebrafish apolipoprotein A-I (apoA-I), apoB, apoE and apoA-IV genes and therefore ensure that they have been correctly named. Their expression patterns throughout development were also analyzed, by whole-mount mRNA in situ hybridization (ISH). The ISH results emphasized the importance of apolipoproteins in transporting yolk and dietary lipids: mRNA expression of all apolipoproteins was observed in the yolk syncytial layer, and intestinal and liver expression was observed from 4-6 days post-fertilization (dpf). Furthermore, real-time PCR confirmed that transcription of three of the four zebrafish apoA-IV genes was increased 4 hours after the onset of a 1-hour high-fat feed. Therefore, we tested the hypothesis that zebrafish ApoA-IV performs a conserved role to that in rat in the regulation of food intake by transiently overexpressing ApoA-IVb.1 in transgenic larvae and quantifying ingestion of co-fed fluorescently labeled fatty acid during a high-fat meal as an indicator of food intake. Indeed, ApoA-IVb.1 overexpression decreased food intake by approximately one-third. This study comprehensively describes the expression and function of eleven zebrafish apolipoproteins and serves as a springboard for future investigations to elucidate their roles in development and disease in the larval zebrafish model.
authors: Carnegie Institution for Science, Department of Embryology, Baltimore, MD 21218, USA.
authors: Jessica P
authors: JP
authors: Otis
authors: Carnegie Institution for Science, Department of Embryology, Baltimore, MD 21218, USA.
authors: Erin M
authors: EM
authors: Zeituni
authors: Carnegie Institution for Science, Department of Embryology, Baltimore, MD 21218, USA Johns Hopkins University, Department of Biology, Baltimore, MD 21218, USA.
authors: James H
authors: JH
authors: Thierer
authors: Carnegie Institution for Science, Department of Embryology, Baltimore, MD 21218, USA.
authors: Jennifer L
authors: JL
authors: Anderson
authors: Carnegie Institution for Science, Department of Embryology, Baltimore, MD 21218, USA.
authors: Alexandria C
authors: AC
authors: Brown
authors: Carnegie Institution for Science, Department of Embryology, Baltimore, MD 21218, USA Johns Hopkins University, Department of Biology, Baltimore, MD 21218, USA.
authors: Erica D
authors: ED
authors: Boehm
authors: Carnegie Institution for Science, Department of Embryology, Baltimore, MD 21218, USA Johns Hopkins University, Department of Biology, Baltimore, MD 21218, USA.
authors: Derek M
authors: DM
authors: Cerchione
authors: Carnegie Institution for Science, Department of Embryology, Baltimore, MD 21218, USA Johns Hopkins University, Department of Biology, Baltimore, MD 21218, USA.
authors: Alexis M
authors: AM
authors: Ceasrine
authors: Weizmann Institute of Science, Department of Biological Regulation, Rehovot 7610001, Israel.
authors: Inbal
authors: I
authors: Avraham-Davidi
authors: Weizmann Institute of Science, Department of Biological Regulation, Rehovot 7610001, Israel.
authors: Hanoch
authors: H
authors: Tempelhof
authors: Weizmann Institute of Science, Department of Biological Regulation, Rehovot 7610001, Israel.
authors: Karina
authors: K
authors: Yaniv
authors: Carnegie Institution for Science, Department of Embryology, Baltimore, MD 21218, USA Johns Hopkins University, Department of Biology, Baltimore, MD 21218, USA farber@ciwemb.edu.
authors: Steven A
authors: SA
authors: Farber
mesh_terms: D000818:Animals; D001054:Apolipoproteins A / Q000235:genetics* / Q000378:metabolism; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D004435:Eating / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D007413:Intestinal Mucosa / Q000378:metabolism; D023421:Models, Animal; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C000603171:Apoa4b protein, zebrafish; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D012333:RNA, Messenger; D029961:Zebrafish Proteins; C022205:apolipoprotein A-IV
keywords: Apolipoprotein A-I; Apolipoprotein A-IV; Apolipoprotein B; Apolipoprotein E; Developmental expression patterns; Regulation of food intake; Zebrafish; mRNA in situ hybridization
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