脂肪细胞Npy4r促进高脂饮食诱导肥胖  

Adipocyte reconstitution of Npy4r gene in Npy4r silenced mice promotes diet-induced obesity

作　　者：王澜 曾帆 黄荣凤 林树 张志辉 李旻典 Lan Wang;Fan Zeng;Rongfeng Huang;Shu Lin;Zhihui Zhang;Min-Dian Li(Department of Cardiovascular Medicine,Center for Circadian Metabolism and Cardiovascular Disease,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing,400038,China)

机构地区：[1]陆军军医大学第一附属医院心血管内科,代谢生物钟与心血管病中心,重庆400038

出　　处：《遗传》2023年第2期144-155,共12页Hereditas（Beijing)

基　　金：国家自然科学基金青年科学基金项目(编号:81900776)资助。

摘　　要：脂肪组织的神经支配与调节在能量代谢稳态的维持中发挥重要作用。神经肽Y(neuropeptide Y, NPY)及其脂肪细胞受体信号通路促进高脂饮食诱导的肥胖,其中NPY受体1(NPY receptor Y1,NPY1R)与受体2(NPY2R)是主要的NPY外周受体。NPY受体4(NPY4R)也在脂肪组织表达,然而尚不清楚其是否参与肥胖的发生发展机制。本研究建立了NPY及其受体的免疫荧光成像技术和脂肪细胞回复性表达Npy4r小鼠。根据对不同部位脂肪组织的荧光显微术观察,发现NPY在肩胛间棕色脂肪和皮下脂肪的围绕血管区域以点状形式表达,NPY系统的各受体在脂肪组织的空间分布上具有明显的组织特异性:NPY1R在棕色脂肪、主动脉周围脂肪和性腺脂肪较为富集,NPY2R在棕色脂肪和主动脉周围脂肪较为富集,NPY4R在棕色脂肪与性腺脂肪较为富集。继而通过比较脂肪细胞回复性表达Npy4r小鼠与全身Npy4r基因静默小鼠在高脂喂食下的体重与糖代谢,发现脂肪细胞Npy4r促进高脂饮食诱导的肥胖(P <0.0001)。本研究明确了NPY及其受体NPY1R、 NPY2R和NPY4R在不同部位脂肪组织的蛋白水平与分布,进而用脂肪细胞特异性地回复表达小鼠模型揭示脂肪细胞Npy4r具有促进高脂饮食诱导肥胖的作用。Neural regulation of adipose tissue is crucial in the homeostasis of energy metabolism. Adipose tissue neuropeptide Y(NPY) and its receptors contribute to the development of diet-induced obesity. NPY1R and NPY2R are major receptors for NPY in peripheral tissues including the adipose tissue. NPY receptor 4(Npy4r) gene is expressed in adipose tissue. However, it is unknown whether Npy4r is involved in the development of diet-induced obesity. Here, we established an immunofluorescence microscopy technique and generated an adipocyte-reconstituted Npy4r gene knockout mouse. Among six adipose depots, we found that NPY is highly expressed around the vasculature in a dot-like fashion in interscapular brown fat and subcutaneous fat, and NPY receptors are expressed in a depot-specific manner. NPY1R is highly expressed in epidydimal fat, interscapular and peri-aortic brown fat, NPY2R in both interscapular and peri-aortic brown fat, and NPY4R in both brown fat and epidydimal fat. Next, we showed that adipocyte-reconstituted expression of Npy4r promoted diet-induced obesity in mice(P < 0.0001). Overall, this study defines the abundance and distribution of NPY and its receptors 1, 2, and 4 in mouse adipose depots, and demonstrates in an adipocyte-reconstituted gene knockout model that adipocyte Npy4r is sufficient to promote diet-induced obesity.

关 键 词：条件性基因回复表达 loxP-STOP-loxP 脂肪细胞 脂肪组织 肥胖 

分 类 号：R589.2[医药卫生—内分泌]