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

Mi Ran Byun; Cham Han Lee; Jun Ha Hwang; A. Rum Kim; Sung Ah Moon; Mi Kyung Sung; Jung Rae Roh; Eun Sook Hwang; Jeong Ho Hong

doi:10.1016/j.ejphar.2013.08.035

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

Mi Ran Byun, Cham Han Lee, Jun Ha Hwang, A. Rum Kim, Sung Ah Moon, Mi Kyung Sung, Jung Rae Roh, Eun Sook Hwang, Jeong Ho Hong

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

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.

Original language	English
Pages (from-to)	181-187
Number of pages	7
Journal	European Journal of Pharmacology
Volume	718
Issue number	1-3
DOIs	https://doi.org/10.1016/j.ejphar.2013.08.035
State	Published - 2013

Bibliographical note

Funding Information:
This work was supported by Research Programs ( 2011–0022926 and 2009-0001197 ) through the National Research Foundation of Korea (NRF) and a Grant from the Marine Biotechnology Program funded by the Land, Transport and Maritime Affairs , Republic of Korea. This work was also supported by a Korea University Grant (to M. R. Byun).

Keywords

Adipogenesis
ERK
PPARγ
Phorbaketal A
TAZ

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ejphar.2013.08.035

Cite this

@article{6aebb7d1b9ef455cb10f8859a133c965,

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.",

keywords = "Adipogenesis, ERK, PPARγ, Phorbaketal A, TAZ",

author = "Byun, {Mi Ran} and Lee, {Cham Han} and Hwang, {Jun Ha} and Kim, {A. Rum} and Moon, {Sung Ah} and Sung, {Mi Kyung} and Roh, {Jung Rae} and Hwang, {Eun Sook} and Hong, {Jeong Ho}",

note = "Funding Information: This work was supported by Research Programs ( 2011–0022926 and 2009-0001197 ) through the National Research Foundation of Korea (NRF) and a Grant from the Marine Biotechnology Program funded by the Land, Transport and Maritime Affairs , Republic of Korea. This work was also supported by a Korea University Grant (to M. R. Byun). ",

year = "2013",

doi = "10.1016/j.ejphar.2013.08.035",

language = "English",

volume = "718",

pages = "181--187",

journal = "European Journal of Pharmacology",

issn = "0014-2999",

publisher = "Elsevier",

number = "1-3",

}

TY - JOUR

T1 - Phorbaketal A inhibits adipogenic differentiation through the suppression of PPARγ-mediated gene transcription by TAZ

AU - Byun, Mi Ran

AU - Lee, Cham Han

AU - Hwang, Jun Ha

AU - Kim, A. Rum

AU - Moon, Sung Ah

AU - Sung, Mi Kyung

AU - Roh, Jung Rae

AU - Hwang, Eun Sook

AU - Hong, Jeong Ho

N1 - Funding Information: This work was supported by Research Programs ( 2011–0022926 and 2009-0001197 ) through the National Research Foundation of Korea (NRF) and a Grant from the Marine Biotechnology Program funded by the Land, Transport and Maritime Affairs , Republic of Korea. This work was also supported by a Korea University Grant (to M. R. Byun).

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Adipogenesis

KW - ERK

KW - PPARγ

KW - Phorbaketal A

KW - TAZ

UR - http://www.scopus.com/inward/record.url?scp=84887118415&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2013.08.035

DO - 10.1016/j.ejphar.2013.08.035

M3 - Article

C2 - 24036109

AN - SCOPUS:84887118415

SN - 0014-2999

VL - 718

SP - 181

EP - 187

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

IS - 1-3

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this