Fatty liver hemorrhagic syndrome (FLHS), a fatty liver disease in laying hens, poses a grave threat to the layer industry, stemming from its ability to trigger an alarming plummet in egg production and usher in acute mortality among laying hens. Increasing evidence suggests that the onset and progression of fatty liver was closely related to mitochondria dysfunction. Sodium butyrate was demonstrated to modulate hepatic lipid metabolism, alleviate oxidative stress and improve mitochondrial dysfunction in vitro and mice models. Nevertheless, there is limited existing research on coated sodium butyrate (CSB) to prevent FLHS in laying hens, and whether and how CSB exerts the anti-FLHS effect still needs to be explored. In this experiment, the FLHS model was induced by administering a high-energy low-protein (HELP) diet in laying hens. The objective was to investigate the effects of CSB on alleviating FLHS with a focus on the role of CSB in modulating mitochondrial function. A total of 288 healthy 28-week-old Huafeng laying hens were arbitrarily allocated into 4 groups with 6 replicates each, namely, the CON group (normal diet), HELP group (HELP diet), CH500 group (500 mg/kg CSB added to HELP diet) and CH750 group (750 mg/kg CSB added to HELP diet). The duration of the trial encompassed a period of 10 weeks. The result revealed that CSB ameliorated the HELP-induced FLHS by improving hepatic steatosis and pathological damage, reducing the gene levels of fatty acid synthesis, and promoting the mRNA levels of key enzymes of fatty acid catabolism. CSB reduced oxidative stress induced by the HELP diet, upregulated the activity of GSH-Px and SOD, and decreased the content of MDA and ROS. CSB also mitigated the HELP diet-induced inflammatory response by blocking TNF-α, IL-1β, and F4/80. In addition, dietary CSB supplementation attenuated HELP-induced activation of the mitochondrial unfolded protein response (UPRmt), mitochondrial damage, and decline of ATPase activity. HELP diet decreased the autophagosome formation, and downregulated LC3B but upregulated p62 protein expression, which CSB administration reversed. CSB reduced HELP-induced apoptosis, as indicated by decreases in the Bax/Bcl-2, Caspase-9, Caspase-3, and Cyt C expression levels. Dietary CSB could ameliorate HELP diet-induced hepatic dysfunction via modulating mitochondrial dynamics, autophagy, and apoptosis in laying hens. Consequently, CSB, as a feed additive, exhibited the capacity to prevent FLHS by modulating autophagy and lipid metabolism.

中文翻译：

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包膜丁酸钠通过调节蛋鸡线粒体动力学、自噬和细胞凋亡改善高能低蛋白饮食引起的肝功能障碍

脂肪肝出血综合征（FLHS）是蛋鸡的一种脂肪肝疾病，对蛋鸡业构成严重威胁，因为它能够引发产蛋量急剧下降并导致蛋鸡急性死亡。越来越多的证据表明脂肪肝的发生和进展与线粒体功能障碍密切相关。在体外和小鼠模型中，丁酸钠被证明可以调节肝脏脂质代谢，减轻氧化应激并改善线粒体功能障碍。然而，现有关于包膜丁酸钠（CSB）预防蛋鸡FLHS的研究有限，CSB是否以及如何发挥抗FLHS作用仍有待探索。在本实验中，通过给蛋鸡施用高能量低蛋白（HELP）饮食来诱导 FLHS 模型。目的是研究 CSB 对减轻 FLHS 的作用，重点是 CSB 在调节线粒体功能中的作用。 288只健康28周龄华丰蛋鸡随机分为4组，每组6个重复，即CON组（正常饲料）、HELP组（HELP饲料）、CH500组（添加500 mg/kg CSB） HELP 饮食）和 CH750 组（HELP 饮食中添加 750 mg/kg CSB）。试验持续时间为 10 周。结果表明，CSB通过改善肝脏脂肪变性和病理损伤、降低脂肪酸合成基因水平、促进脂肪酸分解代谢关键酶的mRNA水平来改善HELP诱导的FLHS。 CSB减少HELP饮食引起的氧化应激，上调GSH-Px和SOD的活性，并降低MDA和ROS的含量。 CSB 还通过阻断 TNF-α、IL-1β 和 F4/80 减轻 HELP 饮食诱导的炎症反应。此外，饮食中补充 CSB 可以减轻 HELP 诱导的线粒体未折叠蛋白反应 (UPRmt) 激活、线粒体损伤和 ATP 酶活性下降。 HELP饮食减少了自噬体的形成，下调了LC3B的表达，但上调了p62蛋白的表达，而CSB给药可逆转这种情况。 CSB 减少了 HELP 诱导的细胞凋亡，如 Bax/Bcl-2、Caspase-9、Caspase-3 和 Cyt C 表达水平降低所示。日粮 CSB 可以通过调节蛋鸡线粒体动力学、自噬和细胞凋亡来改善 HELP 日粮诱导的肝功能障碍。因此，CSB 作为饲料添加剂，表现出通过调节自噬和脂质代谢来预防 FLHS 的能力。