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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.

SUBMITTER: Cheng CF 

PROVIDER: S-EPMC6813364 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Cheng Ching-Feng CF   Ku Hui-Chen HC   Cheng Jing-Jy JJ   Chao Shi-Wei SW   Li Hsiao-Fen HF   Lai Pei-Fang PF   Chang Che-Chang CC   Don Ming-Jaw MJ   Chen Hsi-Hsien HH   Lin Heng H  

Communications biology 20191024


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 (<i>ATF3</i><sup><i>-/-</i></sup> ) 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 isolat  ...[more]

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