Complement C3 participates in the development of goose fatty liver potentially by regulating the expression of FASN and ETNK1.
Complement C3 participates in the development of goose fatty liver potentially by regulating the expression of FASN and ETNK1.
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DOI：
10.1111/asj.13527
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发表时间：
2021-01
期刊：
影响因子：
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通讯作者：
Y. Xing;Cheng Xu;Xiao Lin;Minmeng Zhao;D. Gong;Long Liu;T. Geng
中科院分区：
文献类型：
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作者：
Y. Xing;Cheng Xu;Xiao Lin;Minmeng Zhao;D. Gong;Long Liu;T. Geng
非酒精性脂肪性肝病(NAFLD)发生在人、家畜和家禽中。不同于人NAFLD中补体C3的上调，C3在鹅脂肪肝(GFL)中的表达受到抑制，提示C3在GFL中具有特定的作用。本研究旨在揭示鹅肝细胞在C3表达调控中的独特性，并寻找C3下游基因，以加深对C3在GFL中具体作用的认识。结果表明，与正常饲喂组相比，过量饲喂组鹅的肝脏、肌肉和脂肪组织中C3的表达受到抑制。油酸和胰岛素对鹅原代肝细胞C3表达有抑制作用，而对小鼠原代肝细胞C3表达有诱导作用。共有1123个差异表达基因(DEG)受到C3过表达的影响，主要集中在免疫反应/炎症和分解代谢相关的KEGG途径中。此外，C3的代表性下游基因(FASN和ETNK1)可能介导C3在GFL的发生发展中的作用。总之，GFL中C3的抑制至少部分归因于高胰岛素血症、高脂血症和鹅肝细胞的独特性。补体C3不仅影响肝脏脂肪变性，还影响GFL的炎症/免疫反应。
Non-alcoholic fatty liver disease (NAFLD) occurs in humans, domestic animals and poultry. Different from upregulation of complement C3 in human NAFLD, C3 expression is inhibited in goose fatty liver (GFL), implying a specific role of C3 in GFL. This study was mainly focused on uncovering the uniqueness of goose liver cells in the regulation of C3 expression and identifying the downstream genes of C3 to improve understanding on the specific role of C3 in GFL. The results showed that C3 expression was inhibited in the liver, muscle and fat tissues of the overfed versus control (normally fed) geese. Oleate and insulin could inhibit C3 expression in goose primary hepatocytes but induce it in mouse primary hepatocytes. A total of 1,123 differentially expressed genes (DEGs) were affected by C3 overexpression and were mainly enriched in immune response/inflammation and catabolism-related KEGG pathways. Additionally, the representative downstream genes (FASN and ETNK1) of C3 could mediate the role of C3 in the development of GFL. In conclusion, the suppression of C3 in GFL is at least partially attributed to hyperinsulinemia, hyperlipidemia and uniqueness of goose liver cells. Complement C3 does not only affect hepatic steatosis but also affect inflammation/immune response in GFL.