title: Phorbaketal A inhibits adipogenic differentiation through the suppression of PPARγ-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 adipogenic differentiation, significantly increased during adipogenic differentiation in the presence of phorbaketal A. Phorbaketal A increased the interaction of TAZ and PPARγ to suppress PPARγ (peroxisome proliferator-activated receptor γ) 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 A-induced adipogenic suppression. Thus, the results show that phorbaketal A inhibits adipocyte differentiation through TAZ.
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Korea.
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Byun
authors.forename: Cham Han
authors.initials: CH
authors.lastname: Lee
authors.forename: Jun-Ha
authors.initials: JH
authors.lastname: Hwang
authors.forename: A Rum
authors.initials: AR
authors.lastname: Kim
authors.forename: Sung Ah
authors.initials: SA
authors.lastname: Moon
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Sung
authors.forename: Jung-Rae
authors.initials: JR
authors.lastname: Roh
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Hwang
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Hong
mesh_terms: D000217:Acyltransferases; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D047495:PPAR gamma / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D054830:Sesterterpenes / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma; D054830:Sesterterpenes; D014157:Transcription Factors; C546752:phorbaketal A; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Adipogenesis; ERK; PPARγ; Phorbaketal A; TAZ