title: Lxr regulates lipid metabolic and visual perception pathways during zebrafish development.
abstract: The Liver X Receptors (LXRs) play important roles in multiple metabolic pathways, including fatty acid, cholesterol, carbohydrate and energy metabolism. To expand the knowledge of the functions of LXR signaling during embryonic development, we performed a whole-genome microarray analysis of Lxr target genes in zebrafish larvae treated with either one of the synthetic LXR ligands T0901317 or GW3965. Assessment of the biological processes enriched by differentially expressed genes revealed a prime role for Lxr in regulating lipid metabolic processes, similarly to the function of LXR in mammals. In addition, exposure to the Lxr ligands induced changes in expression of genes in the neural retina and lens of the zebrafish eye, including the photoreceptor guanylate cyclase activators and lens gamma crystallins, suggesting a potential novel role for Lxr in modulating the transcription of genes associated with visual function in zebrafish. The regulation of expression of metabolic genes was phenotypically reflected in an increased absorption of yolk in the zebrafish larvae, and changes in the expression of genes involved in visual perception were associated with morphological alterations in the retina and lens of the developing zebrafish eye. The regulation of expression of both lipid metabolic and eye specific genes was sustained in 1 month old fish. The transcriptional networks demonstrated several conserved effects of LXR activation between zebrafish and mammals, and also identified potential novel functions of Lxr, supporting zebrafish as a promising model for investigating the role of Lxr during development.
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Caroline Lucia
authors.initials: CL
authors.lastname: Pinto
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Sharanya Maanasi
authors.initials: SM
authors.lastname: Kalasekar
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Catherine W
authors.initials: CW
authors.lastname: McCollum
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Riu
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Jonsson
authors.affiliation: Department of Pediatrics, University of Texas Medical School, Houston, TX 77030, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Lopez
authors.affiliation: Department of Pediatrics, University of Texas Medical School, Houston, TX 77030, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Swindell
authors.affiliation: Institut de Recherche en Cancérologie de Montpellier, Institut National de la Santé et de la Recherche Médicale U896, Université Montpellier 1, 34298 Montpellier, France.
authors.forename: Abdel
authors.initials: A
authors.lastname: Bouhlatouf
authors.affiliation: Institut de Recherche en Cancérologie de Montpellier, Institut National de la Santé et de la Recherche Médicale U896, Université Montpellier 1, 34298 Montpellier, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Balaguer
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA. Electronic address: mbondessonbolin@uh.edu.
authors.forename: Maria
authors.initials: M
authors.lastname: Bondesson
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA; Department of Biosciences and Nutrition, Novum, Karolinska Institutet, 141 83 Huddinge, Sweden.
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Gustafsson
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D002460:Cell Line; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D000071518:Liver X Receptors; D020411:Oligonucleotide Array Sequence Analysis; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D055351:Retinal Neurons / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014796:Visual Perception / Q000187:drug effects / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D001565:Benzoates; D001596:Benzylamines; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C473027:GW 3965; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
keywords: Cholesterol metabolism; Eye; Gene regulation; Lens; Lipid metabolism; Liver X receptor; Retina; Yolk; Zebrafish