Echinomycin inhibits adipogenesis in 3T3-L1 cells in a HIF-independent manner

Abstract Obesity is a risk factor for many diseases including diabetes, cancer, cardiovascular disease, and chronic kidney disease. Obesity is characterized by the expansion of white adipose tissue (WAT). Hypertrophy and hyperplasia of adipocytes cause tissue hypoxia followed by inflammation and fib...

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Autores principales:	Junna Yamaguchi, Tetsuhiro Tanaka, Hisako Saito, Seitaro Nomura, Hiroyuki Aburatani, Hironori Waki, Takashi Kadowaki, Masaomi Nangaku
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/25e8daab505341f08980ec84632e7feb
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spelling	oai:doaj.org-article:25e8daab505341f08980ec84632e7feb2021-12-02T11:40:14ZEchinomycin inhibits adipogenesis in 3T3-L1 cells in a HIF-independent manner10.1038/s41598-017-06761-42045-2322https://doaj.org/article/25e8daab505341f08980ec84632e7feb2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06761-4https://doaj.org/toc/2045-2322Abstract Obesity is a risk factor for many diseases including diabetes, cancer, cardiovascular disease, and chronic kidney disease. Obesity is characterized by the expansion of white adipose tissue (WAT). Hypertrophy and hyperplasia of adipocytes cause tissue hypoxia followed by inflammation and fibrosis. Its trigger, preadipocyte differentiation into mature adipocytes, is finely regulated by transcription factors, signal molecules, and cofactors. We found that echinomycin, a potent HIF-1 inhibitor, completely inhibited adipogenesis in 3T3-L1 WAT preadipocytes by affecting the early phase of mitotic clonal expansion. The dose required to exert the effect was surprisingly low and the time was short. Interestingly, its inhibitory effect was independent of HIF-1 pathways. Time-course DNA microarray analysis of drug-treated and untreated preadipocytes extracted a major transcription factor, CCAAT/enhancer-protein β, as a key target of echinomycin. Echinomycin also inhibited adipogenesis and body weight gain in high fat diet mice. These findings highlight a novel role of echinomycin in suppressing adipocyte differentiation and offer a new therapeutic strategy against obesity and diabetes.Junna YamaguchiTetsuhiro TanakaHisako SaitoSeitaro NomuraHiroyuki AburataniHironori WakiTakashi KadowakiMasaomi NangakuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Junna Yamaguchi Tetsuhiro Tanaka Hisako Saito Seitaro Nomura Hiroyuki Aburatani Hironori Waki Takashi Kadowaki Masaomi Nangaku Echinomycin inhibits adipogenesis in 3T3-L1 cells in a HIF-independent manner
description	Abstract Obesity is a risk factor for many diseases including diabetes, cancer, cardiovascular disease, and chronic kidney disease. Obesity is characterized by the expansion of white adipose tissue (WAT). Hypertrophy and hyperplasia of adipocytes cause tissue hypoxia followed by inflammation and fibrosis. Its trigger, preadipocyte differentiation into mature adipocytes, is finely regulated by transcription factors, signal molecules, and cofactors. We found that echinomycin, a potent HIF-1 inhibitor, completely inhibited adipogenesis in 3T3-L1 WAT preadipocytes by affecting the early phase of mitotic clonal expansion. The dose required to exert the effect was surprisingly low and the time was short. Interestingly, its inhibitory effect was independent of HIF-1 pathways. Time-course DNA microarray analysis of drug-treated and untreated preadipocytes extracted a major transcription factor, CCAAT/enhancer-protein β, as a key target of echinomycin. Echinomycin also inhibited adipogenesis and body weight gain in high fat diet mice. These findings highlight a novel role of echinomycin in suppressing adipocyte differentiation and offer a new therapeutic strategy against obesity and diabetes.
format	article
author	Junna Yamaguchi Tetsuhiro Tanaka Hisako Saito Seitaro Nomura Hiroyuki Aburatani Hironori Waki Takashi Kadowaki Masaomi Nangaku
author_facet	Junna Yamaguchi Tetsuhiro Tanaka Hisako Saito Seitaro Nomura Hiroyuki Aburatani Hironori Waki Takashi Kadowaki Masaomi Nangaku
author_sort	Junna Yamaguchi
title	Echinomycin inhibits adipogenesis in 3T3-L1 cells in a HIF-independent manner
title_short	Echinomycin inhibits adipogenesis in 3T3-L1 cells in a HIF-independent manner
title_full	Echinomycin inhibits adipogenesis in 3T3-L1 cells in a HIF-independent manner
title_fullStr	Echinomycin inhibits adipogenesis in 3T3-L1 cells in a HIF-independent manner
title_full_unstemmed	Echinomycin inhibits adipogenesis in 3T3-L1 cells in a HIF-independent manner
title_sort	echinomycin inhibits adipogenesis in 3t3-l1 cells in a hif-independent manner
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/25e8daab505341f08980ec84632e7feb
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Echinomycin inhibits adipogenesis in 3T3-L1 cells in a HIF-independent manner

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