Lxr regulates lipid metabolic and visual perception pathways during zebrafish development.
Lxr regulates lipid metabolic and visual perception pathways during zebrafish development.
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DOI：
10.1016/j.mce.2015.09.030
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发表时间：
2016-01-05
影响因子：
4.1
通讯作者：
Gustafsson JÅ
中科院分区：
文献类型：
--
作者：
Pinto CL;Kalasekar SM;McCollum CW;Riu A;Jonsson P;Lopez J;Swindell EC;Bouhlatouf A;Balaguer P;Bondesson M;Gustafsson JÅ
肝脏 X 受体 (LXR) 在多种代谢途径中发挥重要作用，包括脂肪酸、胆固醇、碳水化合物和能量代谢。为了扩展对胚胎发育过程中 LXR 信号传导功能的了解，我们对用合成 LXR 配体 T0901317 或 GW3965 之一处理的斑马鱼幼虫中的 Lxr 靶基因进行了全基因组微阵列分析。对差异表达基因丰富的生物过程的评估揭示了 Lxr 在调节脂质代谢过程中的主要作用，类似于哺乳动物中 LXR 的功能。此外，暴露于Lxr配体会诱导斑马鱼眼睛神经视网膜和晶状体中基因表达的变化，包括光感受器鸟苷酸环化酶激活剂和晶状体γ晶状体蛋白，这表明Lxr在调节与斑马鱼视觉功能相关的基因转录方面具有潜在的新作用。代谢基因表达的调节在表型上反映在斑马鱼幼虫对卵黄吸收的增加上，而与视觉感知有关的基因表达的变化与发育中的斑马鱼眼睛的视网膜和晶状体的形态变化有关。 1 个月大的鱼中，脂质代谢和眼睛特异性基因的表达调节持续存在。转录网络证明了斑马鱼和哺乳动物之间 LXR 激活的一些保守效应，并且还确定了 Lxr 的潜在新功能，支持斑马鱼作为研究 Lxr 在发育过程中的作用的有前景的模型。
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.