Tian Weihua, Hao Xin, Nie Ruixue, Ling Yao, Zhang Bo, Zhang Hao, Wu Changxin
National Engineering Laboratory for Animal Breeding, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Sanya Institute of China Agricultural University, Hainan, 572025, Sanya, China.
J Anim Sci Biotechnol. 2022 Jul 6;13(1):81. doi: 10.1186/s40104-022-00727-x.
Excessive abdominal fat deposition in commercial broilers presents an obstacle to profitable meat quality, feed utilization, and reproduction. Abdominal fat deposition depends on the proliferation of preadipocytes and their maturation into adipocytes, which involves a cascade of regulatory molecules. Accumulating evidence has shown that microRNAs (miRNAs) serve as post-transcriptional regulators of adipogenic differentiation in mammals. However, the miRNA-mediated molecular mechanisms underlying abdominal fat deposition in chickens are still poorly understood. This study aimed to investigate the biological functions and regulatory mechanism of miRNAs in chicken abdominal adipogenesis.
We established a chicken model of abdominal adipocyte differentiation and analyzed miRNA and mRNA expression in abdominal adipocytes at different stages of differentiation (0, 12, 48, 72, and 120 h). A total of 217 differentially expressed miRNAs (DE-miRNAs) and 3520 differentially expressed genes were identified. Target prediction of DE-miRNAs and functional enrichment analysis revealed that the differentially expressed targets were significantly enriched in lipid metabolism-related signaling pathways, including the PPAR signaling and MAPK signaling pathways. A candidate miRNA, gga-miR-106-5p, exhibited decreased expression during the proliferation and differentiation of abdominal preadipocytes and was downregulated in the abdominal adipose tissues of fat chickens compared to that of lean chickens. gga-miR-106-5p was found to inhibit the proliferation and adipogenic differentiation of chicken abdominal preadipocytes. A dual-luciferase reporter assay suggested that the KLF15 gene, which encodes a transcriptional factor, is a direct target of gga-miR-106-5p. gga-miR-106-5p suppressed the post-transcriptional activity of KLF15, which is an activator of abdominal preadipocyte proliferation and differentiation, as determined with gain- and loss-of-function experiments.
gga-miR-106-5p functions as an inhibitor of abdominal adipogenesis by targeting the KLF15 gene in chickens. These findings not only improve our understanding of the specific functions of miRNAs in avian adipogenesis but also provide potential targets for the genetic improvement of excessive abdominal fat deposition in poultry.
商品肉鸡腹部脂肪过度沉积对肉质、饲料利用率和繁殖性能产生不利影响。腹部脂肪沉积取决于前脂肪细胞的增殖及其向脂肪细胞的成熟过程，这涉及一系列调控分子。越来越多的证据表明，微小RNA（miRNA）在哺乳动物脂肪生成分化过程中发挥转录后调控作用。然而，miRNA介导的鸡腹部脂肪沉积分子机制仍不清楚。本研究旨在探讨miRNA在鸡腹部脂肪生成中的生物学功能及调控机制。
我们建立了鸡腹部脂肪细胞分化模型，并分析了不同分化阶段（0、12、48、72和120小时）腹部脂肪细胞中miRNA和mRNA的表达情况。共鉴定出217个差异表达的miRNA（DE-miRNA）和3520个差异表达基因。对DE-miRNA的靶标预测和功能富集分析表明，差异表达的靶标显著富集于脂质代谢相关信号通路，包括PPAR信号通路和MAPK信号通路。候选miRNA gga-miR-106-5p在腹部前脂肪细胞增殖和分化过程中表达降低，且在脂肪型鸡的腹部脂肪组织中表达低于瘦型鸡。发现gga-miR-106-5p可抑制鸡腹部前脂肪细胞的增殖和脂肪生成分化。双荧光素酶报告基因检测表明，编码转录因子的KLF15基因是gga-miR-106-5p的直接靶标。功能获得和缺失实验表明，gga-miR-106-5p抑制了KLF15的转录后活性，而KLF15是腹部前脂肪细胞增殖和分化的激活因子。
gga-miR-106-5p通过靶向鸡的KLF15基因发挥腹部脂肪生成抑制剂的作用。这些发现不仅增进了我们对miRNA在禽类脂肪生成中特定功能的理解，也为家禽腹部脂肪过度沉积的遗传改良提供了潜在靶点。
