肝脏脂质代谢中断显着导致水禽脂肪堆积过多。研究表明,饮食中补充苏氨酸(Thr)可以改善肝脏脂质代谢紊乱,而Thr缺乏可导致肝脏中的这种代谢紊乱。Thr调节脂质代谢的机制尚不清楚。STAT3(信号转导和转录激活因子3),JAK-STAT(Janus激酶-信号转导和转录激活因子)途径中的关键转录因子,参与各种生物过程,包括脂质和能量代谢。这项研究调查了由于缺乏Thr而导致的STAT3在原代鸭肝细胞中脂质储存增加中的潜在参与。使用小干扰RNA和Stattic,一种特定的STAT3磷酸化抑制剂,我们探讨了STAT3表达模式对Thr调节的肝细胞脂质合成代谢的影响。通过转录组测序,我们发现了与Thr和STAT3共同调节的脂质合成和代谢相关的通路。结果表明,Thr缺乏增加了鸭原代肝细胞的脂质沉积(p<0.01)。STAT3的蛋白质和磷酸化水平的降低直接导致了这种沉积(p<0.01)。转录组学分析显示,Thr缺乏和STAT3敲低共同改变了长链脂肪酸合成和能量代谢相关通路的mRNA表达水平(p<0.05)。Thr缺乏,通过介导STAT3失活,上调的ELOVL7,PPARG,MMP1、MMP13和TIMP4mRNA水平,和下调PTGS2mRNA水平(p<0.01)。总之,这些结果表明,Thr缺乏促进脂质合成,减少脂质分解,并通过下调原代鸭肝细胞中的STAT3活性导致脂质代谢紊乱和甘油三酯沉积。
Liver lipid metabolism disruption significantly contributes to excessive fat buildup in waterfowl. Research suggests that the supplementation of Threonine (Thr) in the diet can improve liver lipid metabolism disorder, while Thr deficiency can lead to such metabolic disorders in the liver. The mechanisms through which Thr regulates lipid metabolism remain unclear. STAT3 (signal transducer and activator of transcription 3), a crucial transcription factor in the JAK-STAT (Janus kinase-signal transducer and activator of transcription) pathway, participates in various biological processes, including lipid and energy metabolism. This research investigates the potential involvement of STAT3 in the increased lipid storage seen in primary duck hepatocytes as a result of a lack of Thr. Using small interfering RNA and Stattic, a specific STAT3 phosphorylation inhibitor, we explored the impact of STAT3 expression patterns on Thr-regulated lipid synthesis metabolism in hepatocytes. Through transcriptome sequencing, we uncovered pathways related to lipid synthesis and metabolism jointly regulated by Thr and STAT3. The results showed that Thr deficiency increases lipid deposition in primary duck hepatocytes (p < 0.01). The decrease in protein and phosphorylation levels of STAT3 directly caused this deposition (p < 0.01). Transcriptomic analysis revealed that Thr deficiency and STAT3 knockdown jointly altered the mRNA expression levels of pathways related to long-chain fatty acid synthesis and energy metabolism (p < 0.05). Thr deficiency, through mediating STAT3 inactivation, upregulated ELOVL7, PPARG, MMP1, MMP13, and TIMP4 mRNA levels, and downregulated PTGS2 mRNA levels (p < 0.01). In summary, these results suggest that Thr deficiency promotes lipid synthesis, reduces lipid breakdown, and leads to lipid metabolism disorders and triglyceride deposition by downregulating STAT3 activity in primary duck hepatocytes.