YAP and ECM Stiffness: Key Drivers of Adipocyte Differentiation and Lipid Accumulation

ECM stiffness significantly influences ADSC differentiation, with YAP, a major transcription factor in the Hippo signaling pathway, playing a pivotal role. This study investigates how ECM stiffness affects ADSC differentiation and its relationship with YAP signaling. Different hydrogel concentrations were used to simulate varying ECM stiffness, and their effects on ADSC differentiation were analyzed through material properties, adipocyte-specific gene expression, lipid droplet staining, YAP localization, and protein levels. Results showed that increasing hydrogel stiffness enhanced adipocyte differentiation in a gradient manner. Inhibition of YAP signaling further increased lipid droplet accumulation, suggesting ECM stiffness affects adipogenesis by modulating YAP signaling and its cytoplasmic phosphorylation. This study reveals the molecular mechanism of ECM stiffness-dependent lipid deposition, highlighting YAP's regulatory role in adipogenesis. These findings provide insights into cell differentiation regulation and have implications for tissue engineering and obesity treatment strategies.