Phorbaketal A inhibits adipogenic differentiation through the suppression of PPAR gamma-mediated gene transcription by TAZ

Abstract

Obesity causes several metabolic diseases, including diabetes. Adipogenic differentiation is an important event for fat formation in obesity. Natural compounds that inhibit adipogenic differentiation are frequently screened to develop therapeutic drugs for treating obesity. Here we investigated the effects of phorbaketal A, a natural marine compound, on adipogenic differentiation of mesenchymal stem cells. Phorbaketal A significantly inhibited adipogenic differentiation as indicated by less fat droplets and decreased expression of adipogenic marker genes. The expression of TAZ (transcriptional coactivator with PDZ-binding motif), an inhibitor of aclipogenic differentiation, significantly increased during adipogenic differentiation in the presence of phorbaketal A. Phorbaketal A increased the interaction of TAZ and PPAR gamma to suppress PPAR gamma (peroxisome proliferator-activated receptor gamma) target gene expression. TAZ-depleted cells showed higher adipogenic potential than that of control cells even in the presence of phorbaketal A During cellular signaling induced by phorbaketal A. ERK (extracellular signal regulated kinase) played an important role in adipogenic suppression; an inhibitor of ERK blocked phorbaketal induced adiponicnic suppression. Thus, the results show that phorbaketal A inhibits adipocyte differentiation through TAZ. (C) 2013 Elsevier B.V. All rights reserved.