Nkx1.2 基因缺失会降低斑马鱼的脂肪产量

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Obesity Pub Date : 2024-05-26 DOI:10.1002/oby.24043

Xinyuan Wang, Xinyi Li, Yunsheng Wang, Zhongmei Ren, Xueqing Du, Jing Gao, Guangdong Ji, Zhenhui Liu

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引用次数: 0

摘要

研究目的本研究旨在探讨具有 NK homeobox 结构域的转录因子 Nkx1-2 在调控脂肪生产中的作用：方法：采用定量实时聚合酶链反应或转录组测序分析基因表达。采用 CRISPR/Cas9 技术生成 nkx1.2 基因敲除斑马鱼和 nkx1.2 基因删除 3T3-L1 细胞。通过电泳迁移实验验证了 Nkx1-2 与启动子的结合：结果：Nkx1-2在斑马鱼脂肪生成的调控过程中起着关键作用。斑马鱼敲除 nkx1.2 会导致体重减轻，同时脂滴生成显著减少，内脏和肝脏脂肪含量降低。此外，与脂质生物合成有关的基因也明显下调。在 3T3-L1 前脂肪细胞中，Nkx1-2 通过与 cebpa 启动子结合，从而激活其转录，诱导分化为成熟脂肪细胞。此外，在 3T3-L1 细胞中，nkx1.2 的表达受 p38 MAPK、JNK 或 Smad2/3 信号通路的调控：我们的研究结果表明，Nkx1-2 是脂肪生成的正向调节因子，在脂肪细胞分化和脂质生物合成中发挥着关键作用。

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Nkx1.2 deletion decreases fat production in zebrafish

Objective

This study aimed to investigate the role of Nkx1-2, a transcription factor with the NK homeobox domain, in the regulation of fat production.

Methods

Gene expression was analyzed using quantitative real-time polymerase chain reaction or transcriptome sequencing. CRISPR/Cas9 technology was employed to generate nkx1.2 knockout zebrafish and nkx1.2-deleted 3T3-L1 cells. Lipid droplet production in zebrafish larvae was visually quantified using Nile red staining, whereas lipid droplets in 3T3-L1 cells were stained with Oil red O. The binding of Nkx1-2 to the promoter was verified through an electrophoretic mobility shift assay experiment.

Results

Nkx1-2 plays crucial roles in the regulation of fat production in zebrafish. Knockout of nkx1.2 in zebrafish leads to weight loss, accompanied by significantly reduced lipid droplet production and decreased visceral and liver fat content. Furthermore, genes related to lipid biosynthesis are significantly downregulated. In 3T3-L1 preadipocytes, Nkx1-2 induces differentiation into mature adipocytes by binding to the cebpa promoter, thereby activating its transcription. Additionally, the expression of nkx1.2 is regulated by the p38 MAPK, JNK, or Smad2/3 signaling pathways in 3T3-L1 cells.

Conclusions

Our findings suggest that Nkx1-2 functions as a positive regulator of fat production, playing a critical role in adipocyte differentiation and lipid biosynthesis.

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来源期刊

Obesity 医学-内分泌学与代谢

CiteScore

11.70

自引率

1.40%

发文量

261

审稿时长

2-4 weeks

期刊介绍： Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.