Liver mRNA expression in 25 mice with or without genetic defects of mitochondrial fatty acid oxidation (Acadl and Acadvl knockout) using RNA sequencing

full title: A mitochondrial long-chain fatty acid oxidation defect in a mouse model leads to dysregulation of plasma long-chain acylcarnitines, dysregulation of plasma amino acids, and an increased reliance on glucocorticoid signaling to maintain euglycemia during fasting. [liver] The liver is a major source of energy substrates during metabolic stress: fasting, prolonged exercise, febrile illness. Fasting-induced hypoglycemia is a characteristic feature of FAO disorders including very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). However, the pathophysiological mechanisms that underlie the diversity of clinical presentation of FAO dysfunction are not known. Here, we investigated the transcriptional response in liver tissue to the FAO defect in a model of VLCADD: the long-chain acyl-CoA dehydrogenase (LCAD) knockout (KO) mouse. We found that differentially expressed genes from the liver were associated with molecular networks annotated for fatty acid oxidation and cholesterol biosynthesis from population-based networks. We analyzed liver mRNA expression in 25 mice with or without genetic defects of mitochondrial fatty acid oxidation (Acadl and Acadvl knockout) using RNA sequencing.完整标题：小鼠模型中线粒体长链脂肪酸氧化缺陷可引发血浆长链酰基肉碱失调、血浆氨基酸失调，并在禁食阶段依赖糖皮质激素信号通路以维持血糖正常水平。【肝脏组织】肝脏是代谢应激（禁食、长时间运动、发热性疾病）过程中能量底物的主要来源。禁食诱导的低血糖是脂肪酸氧化（Fatty Acid Oxidation, FAO）障碍的典型特征，包括极长链酰基辅酶A脱氢酶（very long chain acyl-CoA dehydrogenase, VLCAD）缺乏症（VLCADD）。然而，脂肪酸氧化功能障碍临床表现多样性的病理生理机制尚未明确。本研究以极长链酰基辅酶A脱氢酶缺乏症模型——长链酰基辅酶A脱氢酶（long-chain acyl-CoA dehydrogenase, LCAD）敲除（Knockout, KO）小鼠为研究对象，探究其肝脏组织对脂肪酸氧化缺陷的转录应答反应。研究发现，肝脏组织中的差异表达基因与基于人群的网络注释的脂肪酸氧化及胆固醇生物合成分子网络显著相关。本研究通过RNA测序（RNA-seq）技术，分析了25只存在或不存在线粒体脂肪酸氧化遗传缺陷（Acadl与Acadvl基因敲除）的小鼠的肝脏mRNA表达水平。