Modulation of PPAR signaling disrupts pancreas development in the zebrafish, Danio rerio.
Modulation of PPAR signaling disrupts pancreas development in the zebrafish, Danio rerio.
复制标题
PPAR信号的调节破坏斑马鱼胰腺的发育。
DOI：
10.1016/j.taap.2021.115653
复制
发表时间：
2021-09-01
影响因子：
3.8
通讯作者：
Sant KE
中科院分区：
文献类型：
--
作者：
Venezia O;Islam S;Cho C;Timme-Laragy AR;Sant KE
过氧化物酶体增殖物激活受体(PPAR)是调节脂、糖代谢等过程的转录因子。合成PPAR配体被设计用于治疗代谢性疾病，提供了一种工具来评估PPAR活性与体内胰腺发育之间的关系，这一领域仍然缺乏特征。在这里，我们旨在评估PPAR激动剂和拮抗剂对转基因斑马鱼胚胎的基因表达、胚胎形态和胰腺发育的影响。为了评估发育障碍，我们评估了受精后4天的大体和胰腺形态，以响应PPARα、PPARγ和PPARβ/δ激动剂和拮抗剂在0、0.01、0.1、1和10μM浓度下的发育暴露。除了PPARα激动剂外，所有的配体暴露都导致鱼的长度和卵黄囊面积显著改变。PPARγ激动剂和拮抗剂出现卵黄囊变黑和颅面畸形的发生率较高，而PPARα拮抗剂出现心包水肿和死亡的发生率较高。在PPARγ配体和PPARα激动剂暴露的胚胎中，均观察到内分泌胰腺面积显著减少，其中一些胚胎还表现出异常的内分泌胰腺形态。两个PPARβ/δ配体都导致胰腺外分泌长度缩短和新的异常表型，并扰乱胰腺靶标PDX1、GcgA和Try的基因表达。8dpf时进行脂质染色，发现脂肪堆积改变，与异构体功能一致。这些数据表明，长期接触合成配体可能会导致斑马鱼胚胎的形态和胰腺缺陷。
Peroxisome Proliferator Activated Receptors (PPARs) are transcription factors that regulate processes such as lipid and glucose metabolism. Synthetic PPAR ligands, designed as therapeutics for metabolic disease, provide a tool to assess the relationship between PPAR activity and pancreas development in vivo, an area that remains poorly characterized. Here, we aim to assess the effects of PPAR agonists and antagonists on gene expression, embryonic morphology and pancreas development in transgenic zebrafish embryos. To evaluate developmental perturbations, we assessed gross body and pancreas morphology at 4 days post fertilization (dpf) in response to developmental exposures with PPARα, PPARγ, and PPARβ/δ agonists and antagonists at 0, 0.01, 0.1, 1, and 10 μM concentrations. All ligand exposures, with the exception of the PPARα agonist, resulted in significantly altered fish length and yolk sac area. PPARγ agonist and antagonist had higher incidence of darkened yolk sac and craniofacial deformities, whereas PPARα antagonist had higher incidence of pericardial edema and death. Significantly reduced endocrine pancreas area was observed in both PPARγ ligands and PPARα agonist exposed embryos, some of which also exhibited aberrant endocrine pancreas morphology. Both PPARβ/δ ligands caused reduced exocrine pancreas length and novel aberrant phenotype, and disrupted gene expression of pancreatic targets pdx1, gcga, and try. Lipid staining was performed at 8 dpf and revealed altered lipid accumulation consistent with isoform function. These data indicate chronic exposure to synthetic ligands may induce morphological and pancreatic defects in zebrafish embryos.
登录
查看更多内容
影响因子：
4.6
作者：
Khazaee M;Christie E;Cheng W;Michalsen M;Field J;Ng C
通讯作者：
Ng C
DOI：
10.1017/s2040174415001440
发表时间：
2015-12
影响因子：
1.7
作者：
Desai M;Jellyman JK;Han G;Lane RH;Ross MG
通讯作者：
Ross MG
影响因子：
2.9
作者：
Den Broeder MJ;Kopylova VA;Kamminga LM;Legler J
通讯作者：
Legler J
影响因子：
2.3
作者：
Ibabe, A;Grabenbauer, M;Cajaraville, MP
通讯作者：
Cajaraville, MP
DOI：
10.1073/pnas.012610299
发表时间：
2002-01-08
影响因子：
11.1
作者：
Barak, Y;Liao, D;Evans, RM
通讯作者：
Evans, RM