Transcriptional Inhibition of AGPAT2 Induces Abnormal Lipid Metabolism and Oxidative Stress in the Liver of Nile Tilapia Oreochromis niloticus.
Transcriptional Inhibition of AGPAT2 Induces Abnormal Lipid Metabolism and Oxidative Stress in the Liver of Nile Tilapia Oreochromis niloticus.
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DOI：
10.3390/antiox12030700
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发表时间：
2023-03-12
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影响因子：
--
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酶1-酰基甘油-3-磷酸O-酰基转移酶2（AGPAT 2）是甘油三酯合成中的中间酶。目的研究AGPAT 2对尼罗罗非鱼的调控机制。本研究利用反义RNA技术敲低尼罗罗非鱼AGPAT 2基因。与对照组（转染超纯水或空白表达载体）相比，AGPAT 2基因敲减组的增重率、特定生长率、内脏体细胞指数和肝胰腺体细胞指数显著升高，血清总胆固醇、甘油三酯、葡萄糖、低密度脂蛋白胆固醇和胰岛素水平显著升高。此外，总胆固醇和甘油三酯的含量和超氧化物歧化酶，过氧化氢酶，谷胱甘肽过氧化物酶在肝脏中的丰度显着增加，而丙二醛含量显着降低。在AGPAT 2敲低组中，肝细胞变得严重空泡化并积累脂质。比较转录组分析（AGPAT 2敲低与对照组）显示1789个差异表达基因（DEG），包括AGPAT 2敲低组中472个上调基因和1313个下调基因。功能分析表明，差异表达基因富集的主要途径是脂类代谢和氧化应激，如类固醇合成、不饱和脂肪酸合成、过氧化物酶体增殖物激活受体信号通路和P53通路。我们使用qRT-PCR验证了相关信号通路中13个下游差异基因的mRNA表达变化。这些发现表明，敲低AGPAT 2在罗非鱼中导致脂质代谢异常和氧化应激。
The enzyme 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) is an intermediate enzyme in triglyceride synthesis. The aim was to study the regulatory mechanism of AGPAT2 on Nile tilapia, Oreochromis niloticus. In this study, antisense RNA technology was used to knock-down AGPAT2 in Nile tilapia. Compared with the control groups (transfected with ultrapure water or the blank expression vector), the AGPAT2 knock-down group showed a significantly higher weight gain rate, special growth rate, visceral somatic index, and hepatopancreas somatic index; and significantly increased the total cholesterol, triglycerides, glucose, low-density lipoprotein cholesterol, and insulin levels in serum. In addition, the contents of total cholesterol and triglycerides and the abundance of superoxide dismutase, catalase, and glutathione peroxidase in the liver significantly increased, while the malondialdehyde content significantly decreased. The liver cells became severely vacuolated and accumulated lipids in the AGPAT2 knock-down group. Comparative transcriptome analyses (AGPAT2 knock-down vs. control group) revealed 1789 differentially expressed genes (DEGs), including 472 upregulated genes and 1313 downregulated genes in the AGPAT2 knock-down group. Functional analysis showed that the main pathway of differentially expressed genes enrichment was lipid metabolism and oxidative stress, such as steroid biosynthesis, unsaturated fatty acid biosynthesis, the PPAR signaling pathway, and the P53 pathway. We used qRT-PCR to verify the mRNA expression changes of 13 downstream differential genes in related signaling pathways. These findings demonstrate that knock-down of AGPAT2 in tilapia leads to abnormal lipid metabolism and oxidative stress.
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影响因子：
29
作者：
Cortés VA;Curtis DE;Sukumaran S;Shao X;Parameswara V;Rashid S;Smith AR;Ren J;Esser V;Hammer RE;Agarwal AK;Horton JD;Garg A
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