Hippo-YAP/TAZ signaling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass. Hippo-YAP/TAZ signaling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass

Adipose tissue contributes to systemic energy homeostasis by serving as an energy reservoir and endocrine organ. Coordinated regulation of these functions is essential for metabolic health, but the mechanisms that underlie cross-talk between them have been unknown. Here we show that the transcriptional coregulators YAP and TAZ of the Hippo signaling pathway in adipose tissue control systemic energy balance. Mechanistically, we identify a YAP/TAZ-TEAD axis that upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. Overall design: TAZ (WWTR1) ChIP-seq data of adipocytes differentiated from C3H10T1/2 cells. RNA-seq data obtained from mouse adipose tissue (iWAT)

脂肪组织作为能量储备库与内分泌器官，参与维持全身能量稳态。这些功能的协同调控对代谢健康至关重要，但二者间的交互调控机制此前仍不明晰。本研究证实，脂肪组织内Hippo信号通路（Hippo signaling pathway）的转录共调控因子YAP与TAZ可调控全身能量平衡。机制层面，我们揭示了YAP/TAZ-TEAD轴可通过直接结合瘦素（leptin）基因的上游增强子位点，上调瘦素的表达。实验设计：TAZ（WWTR1）染色质免疫沉淀测序（ChIP-seq）数据取自C3H10T1/2细胞分化的脂肪细胞；RNA测序（RNA-seq）数据获取自小鼠脂肪组织（iWAT）