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

Ching Feng Cheng; Hui Chen Ku; Jing Jy Cheng; Shi Wei Chao; Hsiao Fen Li; Pei Fang Lai; Che Chang Chang; Ming Jaw Don; Hsi Hsien Chen; Heng Lin

doi:10.1038/s42003-019-0624-y

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

Ching Feng Cheng, Hui Chen Ku, Jing Jy Cheng, Shi Wei Chao, Hsiao Fen Li, Pei Fang Lai, Che Chang Chang, Ming Jaw Don, Hsi Hsien Chen, Heng Lin

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

42 Citations (Scopus)

Abstract

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.

Original language	English
Article number	389
Journal	Communications Biology
Volume	2
Issue number	1
DOIs	https://doi.org/10.1038/s42003-019-0624-y
Publication status	Published - Dec 1 2019

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology
General Agricultural and Biological Sciences
Medicine (miscellaneous)

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

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10.1038/s42003-019-0624-y

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title = "Adipocyte browning and resistance to obesity in mice is induced by expression of ATF3",

abstract = "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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AU - Cheng, Ching Feng

AU - Ku, Hui Chen

AU - Cheng, Jing Jy

AU - Chao, Shi Wei

AU - Li, Hsiao Fen

AU - Lai, Pei Fang

AU - Chang, Che Chang

AU - Don, Ming Jaw

AU - Chen, Hsi Hsien

AU - Lin, Heng

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

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

Abstract

ASJC Scopus subject areas

UN SDGs

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