Identification of KMU-3, a novel derivative of gallic acid, as an inhibitor of adipogenesis.

Differentiation of preadipocyte, also called adipogenesis, leads to the phenotype of mature adipocyte. Excessive adipogenesis, however, is largely linked to the development of obesity. Herein we investigated a library of 53 novel chemicals, generated from a number of polyphenolic natural compounds,...

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Autores principales:	Yu-Kyoung Park, Jinho Lee, Victor Sukbong Hong, Jong-Soon Choi, Tae-Yoon Lee, Byeong-Churl Jang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/678ce73cfd0a4c0095959f0a146a25d3
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spelling	oai:doaj.org-article:678ce73cfd0a4c0095959f0a146a25d32021-11-25T05:57:54ZIdentification of KMU-3, a novel derivative of gallic acid, as an inhibitor of adipogenesis.1932-620310.1371/journal.pone.0109344https://doaj.org/article/678ce73cfd0a4c0095959f0a146a25d32014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0109344https://doaj.org/toc/1932-6203Differentiation of preadipocyte, also called adipogenesis, leads to the phenotype of mature adipocyte. Excessive adipogenesis, however, is largely linked to the development of obesity. Herein we investigated a library of 53 novel chemicals, generated from a number of polyphenolic natural compounds, on adipogenesis. Strikingly, among the chemicals tested, KMU-3, a derivative of gallic acid, strongly suppressed lipid accumulation during the differentiation of 3T3-L1 preadipocytes into adipocytes. On mechanistic levels, KMU-3 inhibited expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), and fatty acid synthase (FAS) during adipocyte differentiation. Moreover, KMU-3 reduced expressions of adipokines, including retinol binding protein-4 (RBP-4), leptin, and regulated on activation, normal T cell expressed and secreted (RANTES) during adipocyte differentiation. Of further note, KMU-3 rapidly blocked the phosphorylation of signal transducer and activator of transcription-3 (STAT-3) during the early stage of adipogenesis. Importantly, pharmacological inhibition studies revealed that AG490, a JAK-2/STAT-3 inhibitor suppressed adipogenesis and STAT-3 phosphorylation, implying that early blockage of STAT-3 activity is crucial for the KMU-3-mediated anti-adipogenesis. These findings demonstrate firstly that KMU-3 inhibits adipogenesis by down-regulating STAT-3, PPAR-γ, C/EBP-α, and FAS. This work shows that KMU-3 is an inhibitor of adipogenesis and thus may have therapeutic potential against obesity.Yu-Kyoung ParkJinho LeeVictor Sukbong HongJong-Soon ChoiTae-Yoon LeeByeong-Churl JangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 10, p e109344 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yu-Kyoung Park Jinho Lee Victor Sukbong Hong Jong-Soon Choi Tae-Yoon Lee Byeong-Churl Jang Identification of KMU-3, a novel derivative of gallic acid, as an inhibitor of adipogenesis.
description	Differentiation of preadipocyte, also called adipogenesis, leads to the phenotype of mature adipocyte. Excessive adipogenesis, however, is largely linked to the development of obesity. Herein we investigated a library of 53 novel chemicals, generated from a number of polyphenolic natural compounds, on adipogenesis. Strikingly, among the chemicals tested, KMU-3, a derivative of gallic acid, strongly suppressed lipid accumulation during the differentiation of 3T3-L1 preadipocytes into adipocytes. On mechanistic levels, KMU-3 inhibited expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), and fatty acid synthase (FAS) during adipocyte differentiation. Moreover, KMU-3 reduced expressions of adipokines, including retinol binding protein-4 (RBP-4), leptin, and regulated on activation, normal T cell expressed and secreted (RANTES) during adipocyte differentiation. Of further note, KMU-3 rapidly blocked the phosphorylation of signal transducer and activator of transcription-3 (STAT-3) during the early stage of adipogenesis. Importantly, pharmacological inhibition studies revealed that AG490, a JAK-2/STAT-3 inhibitor suppressed adipogenesis and STAT-3 phosphorylation, implying that early blockage of STAT-3 activity is crucial for the KMU-3-mediated anti-adipogenesis. These findings demonstrate firstly that KMU-3 inhibits adipogenesis by down-regulating STAT-3, PPAR-γ, C/EBP-α, and FAS. This work shows that KMU-3 is an inhibitor of adipogenesis and thus may have therapeutic potential against obesity.
format	article
author	Yu-Kyoung Park Jinho Lee Victor Sukbong Hong Jong-Soon Choi Tae-Yoon Lee Byeong-Churl Jang
author_facet	Yu-Kyoung Park Jinho Lee Victor Sukbong Hong Jong-Soon Choi Tae-Yoon Lee Byeong-Churl Jang
author_sort	Yu-Kyoung Park
title	Identification of KMU-3, a novel derivative of gallic acid, as an inhibitor of adipogenesis.
title_short	Identification of KMU-3, a novel derivative of gallic acid, as an inhibitor of adipogenesis.
title_full	Identification of KMU-3, a novel derivative of gallic acid, as an inhibitor of adipogenesis.
title_fullStr	Identification of KMU-3, a novel derivative of gallic acid, as an inhibitor of adipogenesis.
title_full_unstemmed	Identification of KMU-3, a novel derivative of gallic acid, as an inhibitor of adipogenesis.
title_sort	identification of kmu-3, a novel derivative of gallic acid, as an inhibitor of adipogenesis.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/678ce73cfd0a4c0095959f0a146a25d3
work_keys_str_mv	AT yukyoungpark identificationofkmu3anovelderivativeofgallicacidasaninhibitorofadipogenesis AT jinholee identificationofkmu3anovelderivativeofgallicacidasaninhibitorofadipogenesis AT victorsukbonghong identificationofkmu3anovelderivativeofgallicacidasaninhibitorofadipogenesis AT jongsoonchoi identificationofkmu3anovelderivativeofgallicacidasaninhibitorofadipogenesis AT taeyoonlee identificationofkmu3anovelderivativeofgallicacidasaninhibitorofadipogenesis AT byeongchurljang identificationofkmu3anovelderivativeofgallicacidasaninhibitorofadipogenesis
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Identification of KMU-3, a novel derivative of gallic acid, as an inhibitor of adipogenesis.

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