Functional roles of folic acid in alleviating dexamethasone‐induced fatty liver syndrome in laying hens

Xi Sun, Junjie Ma, Chaohui Wang, Z. Ren, Xin Yang, Xiaojun Yang, Yanli Liu
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Abstract

Fatty liver syndrome (FLS) poses a threat to the poultry industry due to its high occurrence and mortality rate. Folic acid (FA) is a coenzyme crucial for one‐carbon metabolism. However, the mechanism by which FA mitigates FLS in laying hens remains elusive. In this study, 60 21‐week‐old Hy‐Line Brown layers were divided into three groups: the Control (Con) group, the dexamethasone (DXM) group, and the DXM + FA group. Results showed that liver index was significantly increased in the DXM group. H&E and oil red O staining showed the accumulation of lipid droplets in the liver was intensified, confirming the successful establishment of an early fatty liver model without inflammation. FA significantly reversed hepatic lipid deposition, and 57 differentially expressed genes affected by FA were identified in the transcriptome analysis. Their transcriptional and translational levels indicate that in the early FLS, insulin‐like growth factor 2/phosphatidylinositol‐3‐kinase/protein kinase B pathway related to lipid metabolism was activated; folate cycling was inhibited, while endoplasmic reticulum (ER) stress and apoptosis‐related protein abundance were elevated. Dietary FA enhanced the folate circulation, reduced lipogenesis and ER stress, and apoptosis‐related protein expression, thereby mitigating the lipid metabolism disturbance in FLS. Metabolomics identified 151 differential metabolites involved in early FLS occurrence, 34 of which were reversed by FA. Metabolites were also enriched in pathways related to lipid metabolism and hepatic damage. Collectively, these findings can be concluded that FA can alleviate early FLS by affecting lipogenesis, ER stress and apoptosis, which may be mediated by enhanced folate metabolism.
叶酸在缓解地塞米松诱导的蛋鸡脂肪肝综合征中的功能作用
脂肪肝综合症(FLS)发病率和死亡率都很高,对家禽业构成威胁。叶酸(FA)是一种对一碳代谢至关重要的辅酶。然而,叶酸减轻蛋鸡FLS的机制仍未确定。本研究将 60 只 21 周龄褐羽蛋鸡分为三组:对照(Con)组、地塞米松(DXM)组和 DXM + FA 组。结果显示,DXM 组的肝脏指数明显升高。H&E和油红O染色显示,肝脏中脂滴堆积加剧,证实成功建立了无炎症的早期脂肪肝模型。在转录组分析中,发现了57个受FA影响的差异表达基因。它们的转录和翻译水平表明,在早期脂肪肝中,与脂质代谢相关的胰岛素样生长因子2/磷脂酰肌醇-3-激酶/蛋白激酶B通路被激活;叶酸循环被抑制,而内质网(ER)应激和凋亡相关蛋白丰度升高。膳食叶酸增强了叶酸循环,减少了脂肪生成和ER应激以及细胞凋亡相关蛋白的表达,从而缓解了FLS的脂质代谢紊乱。代谢组学发现了 151 种与 FLS 早期发生有关的不同代谢物,其中 34 种被脂肪酸逆转。代谢物还富集在与脂质代谢和肝损伤相关的通路中。总之,这些研究结果可以得出结论:叶酸可以通过影响脂肪生成、ER应激和细胞凋亡来缓解早期FLS,而这可能是通过增强叶酸代谢来实现的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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