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Transcriptomic analysis of the hepatic response to stress in the red cusk-eel (Genypterus chilensis): Insights into lipid metabolism oxidative stress and liver steatosis

机译:转录组学分析红鱼肝脏对应激的反应:对脂质代谢氧化应激和肝脂肪变性的见解

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摘要

Teleosts exhibit a broad divergence in their adaptive response to stress, depending on the magnitude, duration, and frequency of stressors and the species receiving the stimulus. We have previously reported that the red cusk-eel (Genypterus chilensis), an important marine farmed fish, shows a physiological response to stress that results in increased skeletal muscle atrophy mediated by over-expression of components of the ubiquitin proteasome and autophagy-lysosomal systems. To better understand the systemic effects of stress on the red cusk-eel metabolism, the present study assessed the transcriptomic hepatic response to repetitive handling-stress. Using high-throughput RNA-seq, 259 up-regulated transcripts were found, mostly associated with angiogenesis, gluconeogenesis, and triacylglyceride catabolism. Conversely, 293 transcripts were down-regulated, associated to cholesterol biosynthesis, PPARα signaling, fatty acid biosynthesis, and glycolysis. This gene signature was concordant with hepatic metabolite levels and hepatic oxidative damage. Moreover, the increased plasmatic levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase) and AP (alkaline phosphatase), as well as liver histology suggest stress-induced liver steatosis. This study offers an integrative molecular and biochemical analysis of the hepatic response to handling-stress, and reveals unknown aspects of lipid metabolism in a non-model teleost.
机译:硬骨鱼类对压力的适应性反应表现出很大的差异,这取决于应激源和受到刺激的物种的大小,持续时间和频率。我们以前曾报道过,红色的海鳗(Genypterus chilensis)是一种重要的海洋养殖鱼类,显示出对应激的生理反应,导致由泛素蛋白酶体和自噬溶酶体系统的过表达介导的骨骼肌萎缩增加。为了更好地了解应激对红鱼新陈代谢的系统性影响,本研究评估了转录组对反复处理应激的肝脏反应。使用高通量RNA-seq,发现259个上调的转录本,主要与血管生成,糖异生和甘油三酸酯分解代谢有关。相反,下调了293个转录物,与胆固醇的生物合成,PPARα信号传导,脂肪酸的生物合成和糖酵解有关。该基因特征与肝代谢产物水平和肝氧化损伤相一致。此外,血浆AST(天冬氨酸转氨酶),ALT(丙氨酸转氨酶)和AP(碱性磷酸酶)的血浆水平升高,以及肝脏组织学提示应激引起的肝脂肪变性。这项研究提供了肝脏对处理压力反应的综合分子和生化分析,并揭示了非模型硬骨鱼中脂质代谢的未知方面。

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