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Adipocyte browning and resistance to obesity in mice is induced by expression of ATF3

Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. Promoting the browning of white adipose tissue has been suggested as a potential strategy, but a drug still needs to be identified. Here, genetic deletion of activating transcription factor 3 (ATF3(−/−))...

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Autores principales: Cheng, Ching-Feng, Ku, Hui-Chen, Cheng, Jing-Jy, Chao, Shi-Wei, Li, Hsiao-Fen, Lai, Pei-Fang, Chang, Che-Chang, Don, Ming-Jaw, Chen, Hsi-Hsien, Lin, Heng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813364/
https://www.ncbi.nlm.nih.gov/pubmed/31667363
http://dx.doi.org/10.1038/s42003-019-0624-y
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author Cheng, Ching-Feng
Ku, Hui-Chen
Cheng, Jing-Jy
Chao, Shi-Wei
Li, Hsiao-Fen
Lai, Pei-Fang
Chang, Che-Chang
Don, Ming-Jaw
Chen, Hsi-Hsien
Lin, Heng
author_facet Cheng, Ching-Feng
Ku, Hui-Chen
Cheng, Jing-Jy
Chao, Shi-Wei
Li, Hsiao-Fen
Lai, Pei-Fang
Chang, Che-Chang
Don, Ming-Jaw
Chen, Hsi-Hsien
Lin, Heng
author_sort Cheng, Ching-Feng
collection PubMed
description Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. Promoting the browning of white adipose tissue has been suggested as a potential strategy, but a drug still needs to be identified. Here, genetic deletion of activating transcription factor 3 (ATF3(−/−)) in mice under a high-fat diet (HFD) resulted in obesity and insulin resistance, which was abrogated by virus-mediated ATF3 restoration. ST32da, a synthetic ATF3 inducer isolated from Salvia miltiorrhiza, promoted ATF3 expression to downregulate adipokine genes and induce adipocyte browning by suppressing the carbohydrate-responsive element-binding protein–stearoyl-CoA desaturase-1 axis. Furthermore, ST32da increased white adipose tissue browning and reduced lipogenesis in HFD-induced obese mice. The anti-obesity efficacy of oral ST32da administration was similar to that of the clinical drug orlistat. Our study identified the ATF3 inducer ST32da as a promising therapeutic drug for treating diet-induced obesity and related metabolic disorders.
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spelling pubmed-68133642019-10-30 Adipocyte browning and resistance to obesity in mice is induced by expression of ATF3 Cheng, Ching-Feng Ku, Hui-Chen Cheng, Jing-Jy Chao, Shi-Wei Li, Hsiao-Fen Lai, Pei-Fang Chang, Che-Chang Don, Ming-Jaw Chen, Hsi-Hsien Lin, Heng Commun Biol Article Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. Promoting the browning of white adipose tissue has been suggested as a potential strategy, but a drug still needs to be identified. Here, genetic deletion of activating transcription factor 3 (ATF3(−/−)) in mice under a high-fat diet (HFD) resulted in obesity and insulin resistance, which was abrogated by virus-mediated ATF3 restoration. ST32da, a synthetic ATF3 inducer isolated from Salvia miltiorrhiza, promoted ATF3 expression to downregulate adipokine genes and induce adipocyte browning by suppressing the carbohydrate-responsive element-binding protein–stearoyl-CoA desaturase-1 axis. Furthermore, ST32da increased white adipose tissue browning and reduced lipogenesis in HFD-induced obese mice. The anti-obesity efficacy of oral ST32da administration was similar to that of the clinical drug orlistat. Our study identified the ATF3 inducer ST32da as a promising therapeutic drug for treating diet-induced obesity and related metabolic disorders. Nature Publishing Group UK 2019-10-24 /pmc/articles/PMC6813364/ /pubmed/31667363 http://dx.doi.org/10.1038/s42003-019-0624-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Cheng, Ching-Feng
Ku, Hui-Chen
Cheng, Jing-Jy
Chao, Shi-Wei
Li, Hsiao-Fen
Lai, Pei-Fang
Chang, Che-Chang
Don, Ming-Jaw
Chen, Hsi-Hsien
Lin, Heng
Adipocyte browning and resistance to obesity in mice is induced by expression of ATF3
title Adipocyte browning and resistance to obesity in mice is induced by expression of ATF3
title_full Adipocyte browning and resistance to obesity in mice is induced by expression of ATF3
title_fullStr Adipocyte browning and resistance to obesity in mice is induced by expression of ATF3
title_full_unstemmed Adipocyte browning and resistance to obesity in mice is induced by expression of ATF3
title_short Adipocyte browning and resistance to obesity in mice is induced by expression of ATF3
title_sort adipocyte browning and resistance to obesity in mice is induced by expression of atf3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813364/
https://www.ncbi.nlm.nih.gov/pubmed/31667363
http://dx.doi.org/10.1038/s42003-019-0624-y
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