School of Human Environmental Sciences, University of Arkansas, Fayetteville, AR 72701, USA.
Department of Animal Science, University of Arkansas, Fayetteville, AR 72701, USA.
Genes (Basel). 2019 Sep 19;10(9):728. doi: 10.3390/genes10090728.
Mitochondrial nicotinamide adenine dinucleotide phosphate (NADP)-dependent isocitrate dehydrogenase (IDH2) plays a key role in the intermediary metabolism and energy production via catalysing oxidative decarboxylation of isocitrate to α-ketoglutarate in the tricarboxylic acid (TCA) cycle. Despite studies reporting potential interlinks between IDH2 and various diseases, there is lack of effort to comprehensively characterize signature(s) of IDH2 knockout (IDH2 KO) mice. A total of 6583 transcripts were identified from both wild-type (WT) and IDH2 KO mice liver tissues. Afterwards, 167 differentially expressed genes in the IDH2 KO group were short-listed compared to the WT group based on our criteria. The online bioinformatic analyses indicated that lipid metabolism is the most significantly influenced metabolic process in IDH2 KO mice. Moreover, the TR/RXR activation pathway was predicted as the top canonical pathway significantly affected by IDH2 KO. The key transcripts found in the bioinformatic analyses were validated by qPCR analysis, corresponding to the transcriptomics results. Further, an additional qPCR analysis confirmed that IDH2 KO caused a decrease in hepatic de novo lipogenesis via the activation of the fatty acid β-oxidation process. Our unbiased transcriptomics approach and validation experiments suggested that IDH2 might play a key role in homeostasis of lipid metabolism.
线粒体烟酰胺腺嘌呤二核苷酸磷酸（NADP）依赖性异柠檬酸脱氢酶（IDH2）在三羧酸（TCA）循环中通过催化异柠檬酸的氧化脱羧作用生成α-酮戊二酸，从而在中间代谢和能量产生中发挥关键作用。尽管有研究报道 IDH2 与各种疾病之间存在潜在联系，但缺乏全面描述 IDH2 敲除（IDH2 KO）小鼠特征的努力。从野生型（WT）和 IDH2 KO 小鼠的肝脏组织中总共鉴定出 6583 个转录本。随后，根据我们的标准，将 IDH2 KO 组中 167 个差异表达基因与 WT 组进行了比较。在线生物信息学分析表明，脂质代谢是 IDH2 KO 小鼠受影响最显著的代谢过程。此外，TR/RXR 激活途径被预测为受 IDH2 KO 影响最大的顶级经典途径。生物信息学分析中发现的关键转录本通过 qPCR 分析进行了验证，与转录组学结果相对应。此外，进一步的 qPCR 分析证实 IDH2 KO 通过激活脂肪酸β-氧化过程导致肝从头脂肪生成减少。我们的无偏转录组学方法和验证实验表明，IDH2 可能在脂质代谢的动态平衡中发挥关键作用。
