棕色脂肪组织脂代谢重塑的分子机制研究

棕色脂肪组织（BAT）是温度-脂代谢重塑的重要器官，参与了肥胖和代谢类疾病的发生。BAT经历了出生后的发育和成熟才具有抵抗低温和肥胖的功能，但是BAT出生后发育成熟的分子机制还不清楚。本项目拟在单细胞水平上揭示BAT出生后发育成熟的分子机制，拟阐明WTAP在BAT出生后发育和能量代谢中的分子机制。本课题组前期结果提示WTAP在BAT中高表达，在出生后BAT发育过程中和急性冷刺激下显著增加，BAT特异的Wtap基因敲除小鼠（BKO）出现BAT发育异常，脂质异常积累，对冷刺激异常敏感（在3-4小时冷刺激下全部死亡）。本项目拟在此工作基础上，通过能量代谢分析、m6A-RIP-seq、RNA稳定性分析、单细胞RNA-seq、mRNA翻译效率实验等手段，深入研究BAT出生后发育成熟的分子机制以及WTAP在BAT出生后发育和能量代谢中的作用机制，为维持能量代谢平衡提供理论依据和潜在的药物靶点。

Brown adipose tissue (BAT) is an important temperature-lipid metabolism remodeling organ, which is associated with obesity and metabolic diseases. BAT undergoes rapid postnatal development and then protects against cold and obesity into adulthood. However, the molecular mechanisms are largely unknown. In this proposal, we aimed to elucidate the molecular mechanisms of postnatal development of BAT at single-cell level, and we also aimed to explore the role of WTAP in the regulation of postnatal development of BAT and energy metabolism. Our preliminary data showed that WTAP is selectively expressed in BAT. WTAP expression is induced during BAT postnatal development and acute cold challenge. BAT-specific deletion of Wtap impairs BAT development and reduces energy expenditure. In this proposal, we will elucidate the molecular mechanisms of postnatal development of BAT at single-cell level and explore the mechansims of WTAP in the regulation of BAT development and energy metabolism.