Xing Jiani, Zheng Jianying, Cui Sheng, Wang Jinling, Wang Yong, Li Yanyan, Zhu Jiangjiang, Lin Yaqiu
Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu 610041, China.
College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China.
Animals (Basel). 2024 Jul 12;14(14):2051. doi: 10.3390/ani14142051.
As a transcription factor, Nuclear Receptor Subfamily 4 Group A Member 1 (NR4A1) binds to downstream target genes to participate in cell proliferation and cell differentiation. We found that the NR4A1 reached the highest expression at 60 h after the differentiation of goat intramuscular preadipocytes. Overexpression of goat NR4A1 increased the number of intracellular lipid droplets and up-regulated the expression of adipocyte-differentiation-related marker genes including , , , , and , while the relative expression levels of and were significantly decreased. On the contrary, after NR4A1 was knocked down by siRNA, the number of intracellular lipid droplets and the relative expression levels of , , , , and were significantly decreased, and the relative expression levels of and were significantly up-regulated. These results suggest that NR4A1 promotes the differentiation of goat intramuscular preadipocytes. Transcriptome sequencing was carried out after overexpression of goat NR4A1, and the KEGG enrichment analysis result showed that the most differentially expressed genes were related to adipocyte differentiation and were enriched in the PI3K-Akt signaling pathway. LY249002, an inhibitor of the PI3K-Akt signaling pathway, was introduced and decreased the number of intracellular lipid droplets, and the relative expression levels of , , , , , , , , and were decreased accordingly. The above results indicate that overexpression of goat NR4A1 may promote the differentiation of intramuscular preadipocytes through the PI3K-Akt signaling pathway.
作为一种转录因子，核受体亚家族4 A组成员1（NR4A1）与下游靶基因结合，参与细胞增殖和细胞分化。我们发现，山羊肌内前体脂肪细胞分化后60小时，NR4A1表达达到最高。山羊NR4A1过表达增加了细胞内脂滴数量，并上调了包括 、 、 、 、 和 在内的脂肪细胞分化相关标记基因的表达，而 和 的相对表达水平显著降低。相反，用小干扰RNA敲低NR4A1后，细胞内脂滴数量以及 、 、 、 、 和 的相对表达水平显著降低，而 和 的相对表达水平显著上调。这些结果表明，NR4A1促进山羊肌内前体脂肪细胞的分化。对山羊NR4A1过表达后进行转录组测序，KEGG富集分析结果显示，差异表达最显著的基因与脂肪细胞分化相关，且富集于PI3K-Akt信号通路。引入PI3K-Akt信号通路抑制剂LY249002后，细胞内脂滴数量减少， 、 、 、 、 、 、 、 和 的相对表达水平也相应降低。上述结果表明，山羊NR4A1过表达可能通过PI3K-Akt信号通路促进肌内前体脂肪细胞的分化。
