Fig. 8: Hippo pathway and TGFβ signaling synergistically orchestrate adipocyte plasticity and AT fibrosis.

In genetic model, Lats1/2-knockout adipocytes can dedifferentiate into DPP4⁺ progenitors and convert to DPP4⁻ myofibroblasts. Loss of Lats1/2 activates YAP/TAZ that in turn enhance SMAD2 stability through inhibiting its ubiquitination. In the presence of CCL2 and CCL7, monocyte-derived macrophages are recruited to scWAT to produce TGFβ, which activates SMAD2 in dedifferentiated adipocytes to form a complex with YAP/TAZ. The complex translocates into the nucleus to induce transcription of inflammatory and fibrotic genes. In obesity model, the Hippo pathway is inhibited while TGFβ signaling is activated, which impairs adipocyte identity and promotes AT fibrosis. Moreover, CCL2/7 and macrophage form a feedforward loop to amplify inflammatory responses and accelerate AT fibrosis. Together, Hippo pathway inactivation is coupled with TGFβ stimulation to promote AT fibrosis.