YAP1 promotes adipogenesis by regulating the negative feedback mechanism of the Hippo signaling pathway via LATS2.

Abstract

Adipose-derived mesenchymal stem cells (ADSCs) represent a readily accessible and important source of mesenchymal stem cells (MSCs) capable of multilineage differentiation. The Hippo signaling pathway effector YAP has emerged as a pivotal regulator of stem cell fate, yet the specific molecular mechanism by which it modulates lipogenic differentiation of ADSCs has not been clearly defined. In this study, goat ADSCs (gADSCs) isolated from Albas goats in Inner Mongolia were used to investigate the role of YAP1 in adipogenic differentiation. Overexpression of YAP1 significantly promoted the differentiation of ADSCs into adipocytes, an effect accompanied by up-regulation of LATS2 and activation of the negative feedback loop of the Hippo signaling pathway. Elevated LATS2 expression induced YAP phosphorylation, leading to reduced nuclear levels of YAP and TAZ and their subsequent accumulation in the cytoplasm. YAP1 overexpression up-regulated LATS2 expression, which, in turn, enhanced the adipogenic differentiation of ADSCs. This pro-adipogenic effect of YAP1 was dependent on LATS2 kinase activity. These findings indicate that overexpression of YAP1 promotes ADSC adipogenesis by inducing LATS2 expression and activating the Hippo pathway negative feedback loop. Elucidating the molecular role of YAP in ADSC lipogenic differentiation holds great significance for regulating stem cell fate, treating metabolic disorders, and promoting hair follicle growth.