The National Engineering Laboratory for Feed Safety and Pollution Prevention and Controlling, National Development and Reform Commission, China.
Key Laboratory of Molecular Animal Nutrition (Zhejiang University), Ministry of Education, China.
Oxid Med Cell Longev. 2021 Aug 23;2021:4704771. doi: 10.1155/2021/4704771. eCollection 2021.
Valine is an important essential amino acid of laying hens. Dietary supplemented with BCAAs ameliorated gut microbiota, whereas elevated blood levels of BCAAs are positively associated with obesity, insulin resistance, and diabetes in both humans and rodents. General controlled nonrepressed (GCN2) kinase plays a crucial role in regulating intestinal inflammation and hepatic fatty acid homeostasis during amino acids deficiency, while GCN2 deficient results in enhanced intestinal inflammation and developed hepatic steatosis. However, how long-term dietary valine impacts gut health and the development of nonalcoholic fatty liver disease (NAFLD) remains unknown. Hence, in the present study, we elucidated the effects of dietary valine on intestinal barrier function, microbial homeostasis, and the development of NAFLD. A total of 960 healthy 33-weeks-old laying hens were randomly divided into five experimental groups and fed with valine at the following different levels in a feeding trial that lasted 8 weeks: 0.59, 0.64, 0.69, 0.74, and 0.79%, respectively. After 8 weeks of treatment, related tissues and cecal contents were obtained for further analysis. The results showed that diet supplemented with valine ameliorated gut health by improving intestinal villus morphology, enhancing intestinal barrier, decreasing cecum pathogenic bacteria abundances such as and , and inhibiting inflammatory response mediated by GCN2. However, long-term intake of high levels of dietary valine (0.74 and 0.79%) accelerated the development of NAFLD of laying hens by promoting lipogenesis and inhibiting fatty acid oxidation mediated by GCN2-eIF2-ATF4. Furthermore, NAFLD induced by high levels of dietary valine (0.74 and 0.79%) resulted in strengthening oxidative stress, ER stress, and inflammatory response. Our results revealed that high levels of valine are a key regulator of gut health and the adverse metabolic response to NAFLD and suggested reducing dietary valine as a new approach to preventing NAFLD of laying hens.
缬氨酸是产蛋鸡的一种重要必需氨基酸。膳食补充支链氨基酸（BCAAs）可以改善肠道微生物群，而血液中 BCAAs 水平升高与人类和啮齿动物的肥胖、胰岛素抵抗和糖尿病呈正相关。一般控制非抑制（GCN2）激酶在氨基酸缺乏时在调节肠道炎症和肝脏脂肪酸动态平衡中起着至关重要的作用，而 GCN2 缺乏会导致肠道炎症增强和肝脂肪变性发展。然而，长期饮食缬氨酸如何影响肠道健康和非酒精性脂肪性肝病（NAFLD）的发展尚不清楚。因此，在本研究中，我们阐明了饮食缬氨酸对肠道屏障功能、微生物动态平衡和 NAFLD 发展的影响。总共 960 只健康的 33 周龄产蛋鸡在为期 8 周的饲养试验中被随机分为 5 个实验组，分别用以下不同水平的缬氨酸喂养：0.59%、0.64%、0.69%、0.74%和 0.79%。8 周治疗后，获取相关组织和盲肠内容物进行进一步分析。结果表明，饮食补充缬氨酸通过改善肠道绒毛形态、增强肠道屏障、降低盲肠致病性细菌如 和 的丰度、抑制 GCN2 介导的炎症反应来改善肠道健康。然而，长期摄入高水平的膳食缬氨酸（0.74%和 0.79%）通过促进 GCN2-eIF2-ATF4 介导的脂肪生成和抑制脂肪酸氧化来加速产蛋鸡 NAFLD 的发展。此外，高水平膳食缬氨酸（0.74%和 0.79%）诱导的 NAFLD 导致氧化应激、内质网应激和炎症反应增强。我们的研究结果表明，高水平的缬氨酸是肠道健康和对 NAFLD 的不良代谢反应的关键调节剂，并提出减少膳食缬氨酸作为预防产蛋鸡 NAFLD 的新方法。
