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Adipositas - Ursachen, Folgeerkrankungen, Therapie 2018; 12(04): 198-203
DOI: 10.1055/s-0038-1676678
Übersichtsarbeit
Georg Thieme Verlag KG Stuttgart · New York

Der Zebrafisch als in vivo-Modellsystem für Adipositas und assoziierte Erkrankungen

The zebrafish as an in vivo model system for obesity and associated diseases
K. Landgraf
1   Universitätsklinikum Leipzig, Department für Frauen- und Kindermedizin, Zentrum für Pädiatrische Forschung, Leipzig, Germany; Leiter: Prof. Dr. Wieland Kiess
2   Integriertes Forschungs- und Behandlungszentrum (IFB) AdipositasErkrankungen, Universitätsmedizin Leipzig, Germany; Leiter: Prof. Dr. Michael Stumvoll
,
W. Kiess
1   Universitätsklinikum Leipzig, Department für Frauen- und Kindermedizin, Zentrum für Pädiatrische Forschung, Leipzig, Germany; Leiter: Prof. Dr. Wieland Kiess
,
A. Körner
1   Universitätsklinikum Leipzig, Department für Frauen- und Kindermedizin, Zentrum für Pädiatrische Forschung, Leipzig, Germany; Leiter: Prof. Dr. Wieland Kiess
2   Integriertes Forschungs- und Behandlungszentrum (IFB) AdipositasErkrankungen, Universitätsmedizin Leipzig, Germany; Leiter: Prof. Dr. Michael Stumvoll
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Publikationsverlauf

Publikationsdatum:
12. Dezember 2018 (online)

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Zusammenfassung

Viele Erkenntnisse über Mechanismen, die für die Entstehung von Adipositas, und den damit einhergehenden Adipositas-assoziierten Erkrankungen, relevant sind, sind mit Hilfe der Modellorganismen Maus oder Ratte erarbeitet worden. In den letzten Jahren hat sich der Zebrafisch als weiteres, sehr geeignetes in-vivo-Modellsystem etabliert, da er verschiedene Vorteile gegenüber Maus und Ratte und anderen Modellorganismen aufweist. Zudem sind wesentliche Aspekte der Regulation des Energiemetabolismus, welche bei der Entstehung von Adipositas und Adipositas-assoziierten Folgeerkrankungen beim Menschen eine Rolle spielen, im Zebrafisch konserviert. Dies beinhaltet unter anderem Mechanismen der zentralen Regulation des Sättigungsgefühls, der Fettzellentwicklung, der ernährungsbedingten Anhäufung von Fettgewebe sowie der Körperfettverteilung. Aufgrund dessen stellt der Zebrafisch ein geeignetes in vivo-Modellsystem für die Untersuchung von Prozessen dar, welche in die Entstehung von Adipositas und deren Folgeerkrankungen involviert sind.

Summary

Many findings about mechanisms in the field of obesity development and obesity-associated diseases have been identified using mouse or rat model organisms. In recent years, the zebrafish has been established as an additional very useful in vivo model system since it has several advantages to mouse and rat and other model organisms. In addition, important aspects of the regulation of energy metabolism, which are involved in the development of obesity and obesity-associated complications in humans, are preserved in zebrafish. This includes mechanisms of the central regulation of satiety, fat cell development, and dietary accumulation of adipose tissue as well as body fat distribution. As a result, the zebrafish is a suitable in vivo model system for processes involved in the development of obesity and its sequelae.

Schlüsselwörter

Zebrafisch - Tiermodell - Fettgewebe - Adipositas

Keywords

Zebrafish - animal model - adipose tissue - obesity
 

  • Literatur

  • 1 Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C, Muffato M. et al. The zebrafish reference genome sequence and its relationship to the human genome. Nature 2013; 496 (7446): 498-503.
    CrossrefPubMedGoogle Scholar
  • 2 Driever W, Solnica-Krezel L, Schier AF, Neuhauss SC, Malicki J, Stemple DL. et al. A genetic screen for mutations affecting embryogenesis in zebrafish. Development 1996; 123: 37-46.
    PubMedGoogle Scholar
  • 3 Haffter P, Granato M, Brand M, Mullins MC, Hammerschmidt M, Kane DA. et al. The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. Development 1996; 123: 1-36.
    CrossrefPubMedGoogle Scholar
  • 4 Nasevicius A, Ekker SC. Effective targeted gene “knockdown’ in zebrafish. Nat Genet 2000; 26 (02) 216-220.
    CrossrefPubMedGoogle Scholar
  • 5 Hwang WY, Fu Y, Reyon D, Maeder ML, Tsai SQ, Sander JD. et al. Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol 2013; 31 (03) 227-229.
    CrossrefPubMedGoogle Scholar
  • 6 Sander JD, Yeh JR, Peterson RT, Joung JK. Engineering zinc finger nucleases for targeted mutagenesis of zebrafish. Methods Cell Biol 2011; 104: 51-58.
    PubMedGoogle Scholar
  • 7 Kettleborough RN, Busch-Nentwich EM, Harvey SA, Dooley CM, de Bruijn E, van Eeden F. et al. A systematic genome-wide analysis of zebrafish protein-coding gene function. Nature 2013; 496 (7446): 494-497.
    PubMedGoogle Scholar
  • 8 Flynn 3rd EJ, Trent CM, Rawls JF. Ontogeny and nutritional control of adipogenesis in zebrafish (Danio rerio). J Lipid Res 2009; 50 (08) 1641-52.
    CrossrefPubMedGoogle Scholar
  • 9 Minchin JE, Rawls JF. In vivo analysis of white adipose tissue in zebrafish. Methods Cell Biol 2011; 105: 63-86.
    PubMedGoogle Scholar
  • 10 Liu Q, Chen Y, Copeland D, Ball H, Duff RJ, Rockich B. et al. Expression of leptin receptor gene in developing and adult zebrafish. Gen Comp Endocrinol 2010; 166 (02) 346-355.
    CrossrefPubMedGoogle Scholar
  • 11 Zhang C, Forlano PM, Cone RD. AgRP and POMC neurons are hypophysiotropic and coordinately regulate multiple endocrine axes in a larval teleost. Cell Metab 2012; 15 (02) 256-64.
    CrossrefPubMedGoogle Scholar
  • 12 Kawauchi H. Functions of melanin-concentrating hormone in fish. J Exp Zool A Comp Exp Biol 2006; 305 (09) 751-760.
    PubMedGoogle Scholar
  • 13 Farooqi S, O’Rahilly S. Genetics of obesity in humans. Endocr Rev 2006; 27 (07) 710-718.
    CrossrefPubMedGoogle Scholar
  • 14 Fei F, Sun SY, Yao YX, Wang X. [Generation and phenotype analysis of zebrafish mutations of obesity-related genes lepr and mc4r]. Sheng Li Xue Bao 2017; 69 (01) 61-69.
    PubMedGoogle Scholar
  • 15 Song Y, Cone RD. Creation of a genetic model of obesity in a teleost. FASEB J 2007; 21 (09) 2042-2049.
    CrossrefPubMedGoogle Scholar
  • 16 Michel M, Page-McCaw PS, Chen W, Cone RD. Leptin signaling regulates glucose homeostasis, but not adipostasis, in the zebrafish. Proc Natl Acad Sci U S A 2016; 113 (11) 3084-3089.
    CrossrefPubMedGoogle Scholar
  • 17 Schlegel A, Stainier DY. Lessons from ”lower” organisms: what worms, flies, and zebrafish can teach us about human energy metabolism. PLoS Genet 2007; 03 (11) e199.
    CrossrefPubMedGoogle Scholar
  • 18 Imrie D, Sadler KC. White adipose tissue development in zebrafish is regulated by both developmental time and fish size. Dev Dyn 2010; 239 (11) 3013-3023.
    CrossrefPubMedGoogle Scholar
  • 19 Gorissen M, Bernier NJ, Nabuurs SB, Flik G, Huising MO. Two divergent leptin paralogues in zebrafish (Danio rerio) that originate early in teleostean evolution. J Endocrinol 2009; 201 (03) 329-339.
    CrossrefPubMedGoogle Scholar
  • 20 Farber SA, Pack M, Ho SY, Johnson ID, Wagner DS, Dosch R. et al. Genetic analysis of digestive physiology using fluorescent phospholipid reporters. Science 2001; 292 (5520): 1385-1388.
    CrossrefPubMedGoogle Scholar
  • 21 Landgraf K, Strobach A, Kiess W, Korner A. Loss of mtch2 function impairs early development of liver, intestine and visceral adipocytes in zebrafish larvae. FEBS Lett 2016; 590 (17) 2852-2861.
    CrossrefPubMedGoogle Scholar
  • 22 Hsu CC, Lai CY, Lin CY, Yeh KY, Her GM. MicroRNA-27b Depletion Enhances Endotrophic and Intravascular Lipid Accumulation and Induces Adipocyte Hyperplasia in Zebrafish. Int J Mol Sci. 2017 19. (1):
    PubMedGoogle Scholar
  • 23 Leow SC, Poschmann J, Too PG, Yin J, Joseph R, McFarlane C. et al. The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis. Development 2016; 143 (06) 950-961.
    CrossrefPubMedGoogle Scholar
  • 24 Yeh KY, Lai CY, Lin CY, Hsu CC, Lo CP, Her GM. ATF4 overexpression induces early onset of hyperlipidaemia and hepatic steatosis and enhances adipogenesis in zebrafish. Sci Rep 2017; 07 (01) 16362.
    CrossrefPubMedGoogle Scholar
  • 25 Oka T, Nishimura Y, Zang L, Hirano M, Shimada Y, Wang Z. et al. Diet-induced obesity in zebrafish shares common pathophysiological pathways with mammalian obesity. BMC Physiol 2010; 10: 21.
    CrossrefPubMedGoogle Scholar
  • 26 Landgraf K, Schuster S, Meusel A, Garten A, Riemer T, Schleinitz D. et al. Short-term overfeeding of zebrafish with normal or high-fat diet as a model for the development of metabolically healthy versus unhealthy obesity. BMC Physiol 2017; 17 (01) 4.
    CrossrefPubMedGoogle Scholar
  • 27 Minchin JE, Dahlman I, Harvey CJ, Mejhert N, Singh MK, Epstein JA. et al. Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue. Proc Natl Acad Sci U S A 2015; 112 (14) 4363-4368.
    CrossrefPubMedGoogle Scholar
  • 28 Shungin D, Winkler TW, Croteau-Chonka DC, Ferreira T, Locke AE, Magi R. et al. New genetic loci link adipose and insulin biology to body fat distribution. Nature 2015; 518 (7538): 187-196.
    PubMedGoogle Scholar
  • 29 Minchin JE, Rawls JF. In vivo imaging and quantification of regional adiposity in zebrafish. Methods Cell Biol 2017; 138: 3-27.
    PubMedGoogle Scholar
  • 30 Minchin JEN, Rawls JF. A classification system for zebrafish adipose tissues. Dis Model Mech 2017; 10 (06) 797-809.
    CrossrefPubMedGoogle Scholar