Liu Xifeng, Liu Hongkang, Wang Kangwei, Qin Chuanjie, He Yuanfa, Luo Li, Lin Shimei, Chen Yongjun
Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), College of Fisheries, Southwest University, Chongqing 400715, China.
Key Laboratory of Sichuan Province for Fishes Conservation and Utilization in the Upper Reaches of the Yangtze River, Neijiang Normal University, Neijiang 641100, China.
Animals (Basel). 2024 Nov 25;14(23):3394. doi: 10.3390/ani14233394.
The aim of this study was to explain the mechanism underlying the liver injury of juvenile largemouth bass in response to high-starch diet intake. Three diets were formulated with different starch levels, being abbreviated as treatment LS (low starch, 8.13% starch), MS (medium starch, 14.1% starch), and HS (high starch, 20.1% starch), respectively. Fish were fed with their respective diets to apparent satiation for 56 days. The results showed that growth retardation of the HS fish was associated with the reduction in feed intake rather than feed utilization. Histological evaluation of the livers showed that vacuolization was the most prevalent characteristic in the MS fish, while ballooning degeneration, apoptosis, fibrosis, and inflammation were observed in the HS fish. Transcriptome profiling suggested that liver inflammation was mediated by Tlr signal transduction, which activated the Pi3k/Akt/Nfκb signaling axis to promote the release of proinflammatory factors including Il-8 and Ip-10. Hepatocyte apoptosis was mediated by the extrinsic pathway through death receptors including Fas and Tnfr, which coordinately activated the Fadd/caspase-8 death signaling axis. An autonomous inhibition program was identified to counteract the apoptosis signal, and the PI3K/Akt signaling pathway might play an important role in this process through regulating the expression of and . Liver fibrosis was mediated through the Tgf-β and Hh signaling pathways. Upon secretion, Tgf-β1/3 bound to TgfβrI/II complex on the liver cell membrane, which induced the phosphorylation of downstream Smad2/3. When Hh interacted with the membrane receptor Ptc, Smo was activated to initiate signaling, driving the activation of Gli. The activation of both Smad2/3 and Gli promoted their nuclear translocation thereby regulating the transcription of target genes, which resulted in the activation and proliferation of HSCs. The activated HSCs constantly expressed and , which facilitated substantial accumulation of ECM. It should be noted that the molecular mechanism of liver injury in this study was speculated from the transcriptome data thus further experimental verification is warranted for this speculation.
本研究旨在解释幼年华盛顿大口黑鲈摄入高淀粉饮食后肝脏损伤的潜在机制。配制了三种不同淀粉水平的饲料，分别简称为处理组LS（低淀粉，8.13%淀粉）、MS（中淀粉，14.1%淀粉）和HS（高淀粉，20.1%淀粉）。给鱼投喂各自的饲料至明显饱足，持续56天。结果表明，HS组鱼的生长迟缓与采食量减少有关，而非饲料利用率降低。肝脏组织学评估显示，空泡化是MS组鱼最普遍的特征，而HS组鱼则观察到气球样变性、凋亡、纤维化和炎症。转录组分析表明，肝脏炎症由Tlr信号转导介导，其激活Pi3k/Akt/Nfκb信号轴，以促进包括Il-8和Ip-10在内的促炎因子释放。肝细胞凋亡由包括Fas和Tnfr在内的死亡受体通过外在途径介导，这些受体协同激活Fadd/caspase-8死亡信号轴。鉴定出一个自主抑制程序来对抗凋亡信号，PI3K/Akt信号通路可能通过调节 和 的表达在这一过程中发挥重要作用。肝纤维化通过Tgf-β和Hh信号通路介导。分泌后，Tgf-β1/3与肝细胞膜上的TgfβrI/II复合物结合，诱导下游Smad2/3磷酸化。当Hh与膜受体Ptc相互作用时，Smo被激活以启动信号传导，驱动Gli激活。Smad2/3和Gli的激活均促进它们的核转位，从而调节靶基因的转录，导致肝星状细胞（HSC）激活和增殖。激活的HSC持续表达 和 ，促进细胞外基质（ECM）大量积聚。需要注意的是，本研究中肝脏损伤的分子机制是根据转录组数据推测的，因此这一推测有待进一步实验验证。
