6-姜辣素基于TRPVs-[Ca2+]i-UCP1途径激活棕色脂肪产热的机制研究

棕色脂肪组织(BAT)是机体产热耗能的主要器官，利用富含食品功能因子的膳食营养干预方式，促进脂肪棕色化或激活棕色脂肪的产热效应，对维持机体能量稳态和改善糖脂代谢紊乱具有重要意义。申请者前期研究发现，6-姜辣素(6G)作为生姜中主要的多酚活性成分，可激活脂肪细胞中产热靶蛋白解耦联蛋白1（UCP1）的表达，促进脂肪棕色化和氧化呼吸耗能，但其具体分子机制尚未完全阐明。结合文献报道，脂肪细胞中的瞬时受体电位通道蛋白家族（TRPVs）可通过控制脂肪细胞内Ca2+浓度参与调控脂肪棕色化和BAT产热。因此，本研究拟在小鼠模型中系统评价6G激活棕色脂肪产热的作用及途径，同时明确脂肪组织中被6G靶向激活的TRPVs受体通道蛋白。进而在细胞模型中，基于TRPVs-[Ca2+]i-UCP1途径，利用分子生物学技术全面阐明6G激活棕色脂肪产热的分子机制，为6G作为食品功能因子在食品产业的科学应用提供重要理论依据。

Brown adipose tissue (BAT) plays a major role in body's thermogenesis and energy consumption. Promoting browning or BAT thermogenesis by dietary intervention are of great significance to maintain the homeostasis of energy metabolism and regulate the disturbance in lipid-glucose metabolism. Previous studies by the applicant have showed that 6-gingerol (6G), the main phenolic compound in ginger, can promote adipocyte browning and energy consumption by activating the expression of UCP1 in 3T3-L1 adipocytes cell model, but the related molecular mechanism has not been fully elucidated. According to the recent studies, transient receptor potential vanilloid proteins (TRPVs) could regulate the concentration of Ca2+ in adipocytes, which is involved in the promotion of adipose browning and BAT thermogenesis. Therefore, this study aims to evaluate the thermogenic effect of 6G and identify the TRPVs receptor channels specifically activated by 6G in adipose tissue by using a mouse model. Furthermore, based on the TRPVs-[Ca2+]i-UCP1 pathway, the molecular mechanism of 6G activating brown fat thermogenesis will be fully elucidated in the beige/brown adipocyte model by using molecular biology technique. This study will provide an important theoretical basis for the application of 6-gingerol as food functional factor in the food industry.