长链非编码RNA-lncDGAT2调控山羊棕色脂肪产热的作用机制

棕色脂肪在动物的非颤栗性产热过程中起着重要的作用，并且与羔羊的早期生长发育有着密切的关系。申请人前期研究发现一个山羊棕色脂肪特异表达的长链非编码RNA（lncDGAT2），过表达lncDGAT2促进棕色脂肪细胞的产热而不影响脂肪细胞的分化，并且显著上调解偶联蛋白UCP1基因的表达，但这种内在的调控机制仍不清楚。为此，本项目拟首先明确lncDGAT2在山羊棕色脂肪细胞产热过程中的作用；进一步验证lncDGAT2是否通过与RNA结合蛋白（hnRNPU）的结合，进而招募棕色脂肪转录因子C/EBPβ，以核糖核蛋白复合物的形式结合到UCP1基因的启动子，调控目的基因的转录；最后从活体水平研究lncDGAT2对棕色脂肪产热的作用和生物学功能。项目研究结果不仅能揭示lncDGAT2在调控山羊棕色脂肪产热过程中的作用机制，同时也为研究棕色脂肪在羔羊生长发育过程中的作用提供理论基础。

Brown adipose tissue plays an important role in the nonshivering thermogenesis and is related to the early growth and development of goat kids. In our previous study, a novel brown adipose-enriched LncRNA (lncDGAT2) was identified. In addition, overexpression of lncDGAT2 promoted brown adipocyte thermogenesis rather than differentiation and upregulated the expression level of UCP1 gene. However, the underlying molecular mechanisms remain unclear. In this study, we first verify the role of lncDGAT2 in the thermogenesis of goat brown adipocytes. Then we will investigate whether lncDGAT2 and hnRNP U bind to each other, and then recruit brown fat specific transcription factor C/EBPβ, which then form ribonucleoprotein complex to control the transcription of UCP1 gene. Finally, the biological function of lncDGAT2 on the thermogenesis of brown adipose tissue will be studied in vivo. These studies can not only reveal the mechanism of lncDGAT2 in regulation of goat brown adipose thermogenesis, but also provide a theoretical basis for further studies on the role of brown fat in the growth of goat kids.