A considerable number of muscle development-related genes were differentially expressed in the early stage of avian adipocyte differentiation. However, the functions of them in adipocyte differentiation remain largely known. In this study, the myoblast determination protein 1 (MYOD1) was selected as a representative of muscle development. We investigated its expression, function, and regulation in avian adipocyte differentiation. The expression of MYOD1 decreased significantly in the early stage of avian adipocyte differentiation. CRISPR/Cas9-mediated deletion of MYOD1 induced adipocyte differentiation, whereas over-expression of MYOD1 inhibited adipogenesis. The mRNA-seq data showed that MYOD1 could perturb the lipid biosynthetic process during differentiation. Our results showed that MYOD1 directly up-regulates the miR-206 expression by binding the upstream 1200 bp region of miR-206. Then, over-expression of miR-206 can inhibit the adipogenesis. Furthermore, MYOD1 affected the expression of endogenous miR-206 and its target gene Kruppel-like factor 4 (KLF4), which is an important activator of adipogenesis. Accordingly, the inhibition of miR-206 or over-expression of KLF4 could counteract the inhibitory effect of MYOD1 on adipocyte differentiation. Our results establish that MYOD1 inhibits adipocyte differentiation by up-regulating miR-206 to suppress the KLF4 expression. These findings identify a novel function of MYOD1 in adipocyte differentiation, suggesting a potential role in body-fat distribution regulation.

中文翻译：

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MYOD1 通过 miRNA-206/KLF4 轴抑制禽类脂肪细胞分化

相当多的肌肉发育相关基因在禽类脂肪细胞分化早期存在差异表达。然而，它们在脂肪细胞分化中的功能仍然广为人知。本研究选择成肌细胞决定蛋白1（MYOD1）作为肌肉发育的代表。我们研究了其在禽类脂肪细胞分化中的表达、功能和调节。禽类脂肪细胞分化早期MYOD1表达显着下降。CRISPR/Cas9介导的MYOD1缺失诱导脂肪细胞分化，而MYOD1的过度表达则抑制脂肪生成。mRNA-seq 数据显示 MYOD1 可以扰乱分化过程中的脂质生物合成过程。我们的结果表明，MYOD1 通过结合 miR-206 的上游 1200 bp 区域直接上调 miR-206 的表达。然后，miR-206的过度表达可以抑制脂肪形成。此外，MYOD1影响内源性miR-206及其靶基因Kruppel样因子4（KLF4）的表达，KLF4是脂肪生成的重要激活剂。因此，抑制miR-206或过表达KLF4可以抵消MYOD1对脂肪细胞分化的抑制作用。我们的结果表明，MYOD1 通过上调 miR-206 抑制 KLF4 表达来抑制脂肪细胞分化。这些发现确定了 MYOD1 在脂肪细胞分化中的新功能，表明其在身体脂肪分布调节中的潜在作用。