title: Dwarfism and increased adiposity in the gh1 mutant zebrafish vizzini.
abstract: Somatic growth and adipogenesis are closely associated with the development of obesity in humans. In this study, we identify a zebrafish mutant, vizzini, that exhibits both a severe defect in somatic growth and increased accumulation of adipose tissue. Positional cloning of vizzini revealed a premature stop codon in gh1. Although the effects of GH are largely through igfs in mammals, we found no decrease in the expression of igf transcripts in gh1 mutants during larval development. As development progressed, however, we found overall growth to be progressively retarded and the attainment of specific developmental stages to occur at abnormally small body sizes relative to wild type. Moreover, both subcutaneous (sc) and visceral adipose tissues underwent precocious development in vizzini mutants, and at maturity, the sizes of different fat deposits were greatly expanded relative to wild type. In vivo confocal imaging of sc adipose tissue (SAT) expansion revealed that vizzini mutants exhibit extreme enlargement of adipocyte lipid droplets without a corresponding increase in lipid droplet number. These findings suggest that GH1 signaling restricts SAT hypertrophy in zebrafish. Finally, nutrient deprivation of vizzini mutants revealed that SAT mobilization was greatly diminished during caloric restriction, further implicating GH1 signaling in adipose tissue homeostasis. Overall, the zebrafish gh1 mutant, vizzini, exhibits decreased somatic growth, increased adipose tissue accumulation, and disrupted adipose plasticity after nutrient deprivation and represents a novel model to investigate the in vivo dynamics of vertebrate obesity.
authors: Department of Biology, University of Washington, Box 351800, Seattle, Washington 98195-1800, USA.
authors: Sarah K
authors: SK
authors: McMenamin
authors: James E N
authors: JE
authors: Minchin
authors: Tiffany N
authors: TN
authors: Gordon
authors: John F
authors: JF
authors: Rawls
authors: David M
authors: DM
authors: Parichy
mesh_terms: D017667:Adipocytes / Q000473:pathology*; D050156:Adipogenesis / Q000235:genetics*; D050154:Adiposity / Q000235:genetics*; D000818:Animals; D018389:Codon, Nonsense; D004392:Dwarfism / Q000235:genetics*; D013006:Growth Hormone / Q000235:genetics*; D006984:Hypertrophy; D009765:Obesity / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D013006:Growth Hormone