title: Liver immune responses to inflammatory stimuli in a diet-induced obesity model of zebrafish.
abstract: Obesity- and metabolic syndrome-related diseases are becoming important medical challenges for the western world. Non-alcoholic fatty liver disease (NAFLD) is a manifestation of these altered conditions in the liver, and inflammation appears to be a factor that is tightly connected to its evolution. In this study, we used a diet-induced obesity approach in zebrafish (Danio rerio) based on overfeeding to analyze liver transcriptomic modulation in the disease and to determine how obesity affects the immune response against an acute inflammatory stimulus such as lipopolysaccharide (LPS). Overfed zebrafish developed an obese phenotype, showed signs of liver steatosis, and its modulation profile resembled that observed in humans, with overexpression of tac4, col4a3, col4a5, lysyl oxidases, and genes involved in retinoid metabolism. In response to LPS, healthy fish exhibited a typical host defense reaction comparable to that which occurs in mammals, whereas there was no significant gene modulation when comparing expression in the liver of LPS-stimulated and non-stimulated obese zebrafish at the same statistical level. The stimulation of obese fish represents a double-hit to the already damaged liver and can help understand the evolution of the disease. Finally, a comparison of the differential gene activation between stimulated healthy and obese zebrafish revealed the expected difference in the metabolic state between healthy and diseased liver. The differentially modulated genes are currently being studied as putative new pathological markers in NAFLD-stimulated liver in humans.
authors.affiliation: Instituto de Investigaciones MarinasCSIC, Eduardo Cabello 6, 36208 Vigo, SpainHospital Universitario Fundación AlcorcónMadrid, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Forn-Cuní
authors.affiliation: Instituto de Investigaciones MarinasCSIC, Eduardo Cabello 6, 36208 Vigo, SpainHospital Universitario Fundación AlcorcónMadrid, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Varela
authors.affiliation: Instituto de Investigaciones MarinasCSIC, Eduardo Cabello 6, 36208 Vigo, SpainHospital Universitario Fundación AlcorcónMadrid, Spain.
authors.forename: Conrado M
authors.initials: CM
authors.lastname: Fernández-Rodríguez
authors.affiliation: Instituto de Investigaciones MarinasCSIC, Eduardo Cabello 6, 36208 Vigo, SpainHospital Universitario Fundación AlcorcónMadrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Figueras
authors.affiliation: Instituto de Investigaciones MarinasCSIC, Eduardo Cabello 6, 36208 Vigo, SpainHospital Universitario Fundación AlcorcónMadrid, Spain virus@iim.csic.es.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Novoa
mesh_terms: D000818:Animals; D004032:Diet; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008070:Lipopolysaccharides; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D046228:Microarray Analysis; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides
keywords: DIO; NAFLD; inflammation; zebrafish