Zhang Xiao-Juan, Zhou Li, Lu Wei-Jia, Du Wen-Xuan, Mi Xiang-Yuan, Li Zhi, Li Xi-Yin, Wang Zhong-Wei, Wang Yang, Duan Ming, Gui Jian-Fang
College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Wuhan, 430072, Hubei, China.
BMC Genomics. 2021 May 5;22(1):328. doi: 10.1186/s12864-021-07621-2.
Fatty liver has become a main problem that causes huge economic losses in many aquaculture modes. It is a common physiological or pathological phenomenon in aquaculture, but the causes and occurring mechanism are remaining enigmatic.
Each three liver samples from the control group of allogynogenetic gibel carp with normal liver and the overfeeding group with fatty liver were collected randomly for the detailed comparison of histological structure, lipid accumulation, transcriptomic profile, latent pathway identification analysis (LPIA), marker gene expression, and hepatocyte mitochondria analyses.
Compared to normal liver, larger hepatocytes and more lipid accumulation were observed in fatty liver. Transcriptomic analysis between fatty liver and normal liver showed a totally different transcriptional trajectory. GO terms and KEGG pathways analyses revealed several enriched pathways in fatty liver, such as lipid biosynthesis, degradation accumulation, peroxidation, or metabolism and redox balance activities. LPIA identified an activated ferroptosis pathway in the fatty liver. qPCR analysis confirmed that gpx4, a negative regulator of ferroptosis, was significantly downregulated while the other three positively regulated marker genes, such as acsl4, tfr1 and gcl, were upregulated in fatty liver. Moreover, the hepatocytes of fatty liver had more condensed mitochondria and some of their outer membranes were almost ruptured.
We reveal an association between ferroptosis and fish fatty liver for the first time, suggesting that ferroptosis might be activated in liver fatty. Therefore, the current study provides a clue for future studies on fish fatty liver problems.
脂肪肝已成为许多水产养殖模式中造成巨大经济损失的主要问题。它是水产养殖中常见的生理或病理现象，但其病因和发生机制仍不清楚。
从具有正常肝脏的异育银鲫对照组和患有脂肪肝的过度投喂组中随机各采集三个肝脏样本，用于详细比较组织结构、脂质积累、转录组图谱、潜在途径识别分析（LPIA）、标记基因表达和肝细胞线粒体分析。
与正常肝脏相比，脂肪肝中观察到更大的肝细胞和更多的脂质积累。脂肪肝与正常肝脏之间的转录组分析显示出完全不同的转录轨迹。基因本体（GO）术语和京都基因与基因组百科全书（KEGG）通路分析揭示了脂肪肝中一些富集的通路，如脂质生物合成、降解积累、过氧化或代谢以及氧化还原平衡活动。LPIA确定了脂肪肝中一条激活的铁死亡途径。定量聚合酶链反应（qPCR）分析证实，铁死亡的负调节因子谷胱甘肽过氧化物酶4（gpx4）在脂肪肝中显著下调，而其他三个正调节标记基因，如长链脂酰辅酶A合成酶4（acsl4）、转铁蛋白受体1（tfr1）和谷氨酸半胱氨酸连接酶（gcl）在脂肪肝中上调。此外，脂肪肝的肝细胞线粒体更浓缩，部分线粒体外膜几乎破裂。
我们首次揭示了铁死亡与鱼类脂肪肝之间的关联，表明肝脏脂肪变性时铁死亡可能被激活。因此，本研究为未来鱼类脂肪肝问题的研究提供了线索。
