PUBLICATION

Lxr regulates lipid metabolic and visual perception pathways during zebrafish development

Authors

Pinto, C.L., Kalasekar, S.M., McCollum, C.W., Riu, A., Jonsson, P., Lopez, J., Swindell, E., Bouhlatouf, A., Balaguer, P., Bondesson, M., Gustafsson, J.Å.

ID

ZDB-PUB-151003-6

Date

2016

Source

Molecular and Cellular Endocrinology 419: 29-43 (Journal)

Registered Authors

Swindell, Eric C.

Keywords

Cholesterol Metabolism, Eye, Gene Regulation, Lens, Lipid Metabolism, Liver X receptor, Retina, Yolk, Zebrafish

Datasets

GEO:GSE59031

MeSH Terms

Gene Expression Profiling
Visual Perception/drug effects
Visual Perception/genetics*
Retinal Neurons/drug effects
Retinal Neurons/metabolism
Zebrafish/genetics
Zebrafish/growth & development*
Hydrocarbons, Fluorinated/pharmacology
Sulfonamides/pharmacology
Lipid Metabolism*/drug effects
Benzylamines/pharmacology
Oligonucleotide Array Sequence Analysis
Orphan Nuclear Receptors/genetics
Orphan Nuclear Receptors/metabolism*
Cell Line
Benzoates/pharmacology
Liver X Receptors
Animals
Lens, Crystalline/drug effects
Lens, Crystalline/metabolism
Gene Expression Regulation, Developmental/drug effects

(all 21)

PubMed

26427652 Full text @ Mol. Cell. Endocrinol.

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.

Genes / Markers

Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB/TU	chemical treatment by environment: liver X receptor agonist	Days 30-44	whole organism crygs2 expression increased amount, abnormal	Fig. 8
AB/TU	chemical treatment by environment: liver X receptor agonist	Days 30-44	whole organism elovl2 expression increased amount, abnormal	Fig. 7
AB/TU	chemical treatment by environment: liver X receptor agonist	Days 30-44	whole organism fads2 expression increased amount, abnormal	Fig. 7
AB/TU	chemical treatment by environment: liver X receptor agonist	Days 30-44	whole organism fasn expression increased amount, abnormal	Fig. 7
AB/TU	chemical treatment by environment: liver X receptor agonist	Days 30-44	whole organism grk7a expression decreased amount, abnormal	Fig. 8
AB/TU	chemical treatment by environment: liver X receptor agonist	Days 30-44	whole organism guca1b expression decreased amount, abnormal	Fig. 8
AB/TU	chemical treatment by environment: liver X receptor agonist	Days 30-44	whole organism guca1d expression decreased amount, abnormal	Fig. 8
AB/TU	chemical treatment by environment: liver X receptor agonist	Days 30-44	whole organism guca1g expression decreased amount, abnormal	Fig. 8
AB/TU	chemical treatment by environment: liver X receptor agonist	Days 30-44	whole organism rbp3 expression decreased amount, abnormal	Fig. 8
AB/TU	chemical treatment by environment: liver X receptor agonist	Days 30-44	whole organism rgs9a expression decreased amount, abnormal	Fig. 8

1 - 10 of 54

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Mutations / Transgenics

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
nr1h3	MO2-nr1h3	MRPHLNO

Fish

Fish
AB/TU
WIK
WT
WT + MO2-nr1h3

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Pinto et al., 2016 ZDB-PUB-151003-6 PMID:26427652

Lxr regulates lipid metabolic and visual perception pathways during zebrafish development

Pinto et al., 2016

ZDB-PUB-151003-6
PMID:26427652