Zhuang Zhong, Wu Lei, Jia Wenqian, Li Yongpeng, Lu Yijia, Xu Minghong, Bai Hao, Bi Yulin, Wang Zhixiu, Chen Shihao, Chang Guobin, Jiang Yong
Key Laboratory for Animal Genetics & Molecular Breeding of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.
Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Institutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou 225009, China.
Poult Sci. 2024 Dec;103(12):104444. doi: 10.1016/j.psj.2024.104444. Epub 2024 Oct 28.
Dietary threonine (Thr) is known to influence fat deposition in poultry, but the precise mechanisms behind its regulatory effects on hepatic lipid metabolism remain elusive. Prior research indicated that including supplemental Thr in the feed may influence STAT3 (Signal Transducer and Activator of Transcription 3) levels in the liver of meat ducks. Numerous studies have recorded the function of STAT3 in regulating fatty acid (FA) metabolism in mammals. The primary objective of this study was to investigate whether Thr influences FA metabolism and triglycerides (TG) deposition in duck liver by regulating STAT3 expression. Primary hepatocytes were isolated from duck embryos and treated for 36 h with different doses of Thr (0, 10, 25, 50, 200 μM) in vitro or with a constructed STAT3 overexpression plasmid to examine the content of FAs and TG. RNA-seq was used to detect changes in gene expression in hepatocytes following STAT3 overexpression. The results demonstrated that both the exogenous addition of Thr and the overexpression of STAT3 significantly suppressed the capacity of hepatocytes for FAs deposition (P < 0.05). The overexpression of STAT3 also inhibited TG accumulation under conditions in response to Thr deficiency (P < 0.01). Transcriptomic analyses indicated that the overexpression of STAT3 inhibits the activity of triglyceride metabolism and unsaturated fatty acid biosynthesis (P < 0.01). Finally, a dual-luciferase reporter test demonstrated that STAT3 may systematically target and inhibit SCD1 transcription (P < 0.01). The present study indicates that supplemental Thr (50 μM) inhibits hepatic FA deposition via the STAT3-SCD1 pathway. This work enhances our comprehension of the functional roles of Thr and STAT3 in modulating lipid metabolism within duck livers. Moreover, it provides a partial theoretical foundation for the nutritional prevention and pharmacological intervention of lipid metabolism disorders in poultry.
已知日粮中的苏氨酸（Thr）会影响家禽的脂肪沉积，但其对肝脏脂质代谢调节作用背后的确切机制仍不清楚。先前的研究表明，在饲料中添加苏氨酸可能会影响肉鸭肝脏中信号转导与转录激活因子3（STAT3）的水平。许多研究记录了STAT3在调节哺乳动物脂肪酸（FA）代谢中的作用。本研究的主要目的是探讨苏氨酸是否通过调节STAT3表达来影响鸭肝脏中的脂肪酸代谢和甘油三酯（TG）沉积。从鸭胚胎中分离出原代肝细胞，在体外分别用不同剂量的苏氨酸（0、10、25、50、200μM）处理36小时，或用构建的STAT3过表达质粒处理，以检测脂肪酸和甘油三酯的含量。利用RNA测序检测STAT3过表达后肝细胞中基因表达的变化。结果表明，外源添加苏氨酸和STAT3过表达均显著抑制了肝细胞的脂肪酸沉积能力（P<0.05）。在苏氨酸缺乏的条件下，STAT3过表达也抑制了甘油三酯的积累（P<0.01）。转录组分析表明，STAT3过表达抑制了甘油三酯代谢和不饱和脂肪酸生物合成的活性（P<0.01）。最后，双荧光素酶报告基因检测表明，STAT3可能系统性地靶向并抑制硬脂酰辅酶A去饱和酶1（SCD1）的转录（P<0.01）。本研究表明，添加苏氨酸（50μM）通过STAT3-SCD1途径抑制肝脏脂肪酸沉积。这项工作增强了我们对苏氨酸和STAT3在调节鸭肝脏脂质代谢中功能作用的理解。此外，它为家禽脂质代谢紊乱的营养预防和药物干预提供了部分理论基础。
