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. 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（adipose tissue）可作为能量储存库与内分泌器官，参与全身能量稳态的维持。这两类功能的协同调控对于代谢健康至关重要，但二者间信号串扰的潜在分子机制此前尚不明确。本研究证实，脂肪组织内Hippo信号通路（Hippo signaling pathway）的转录共调节因子YAP与TAZ可调控全身能量平衡。从机制层面分析，本研究发现YAP/TAZ-TEAD信号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。本研究包含两组组学数据：一是从C3H10T1/2细胞诱导分化得到的脂肪细胞的TAZ（WWTR1）染色质免疫共沉淀测序（ChIP-seq）数据；二是从小鼠脂肪组织（iWAT）获取的RNA测序（RNA-seq）数据。