The ATF3 inducer protects against diet-induced obesity via suppressing adipocyte adipogenesis and promoting lipolysis and browning

In this study, we investigated whether the activating transcription factor 3 (ATF3) inducer ST32db, a synthetic compound with a chemical structure similar to that of native Danshen compounds, exerts an anti-obesity effect in 3T3-L1 white preadipocytes, D16 beige cells, and mice with obesity induced...

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Autores principales:	Hui-Chen Ku, Tsai-Yun Chan, Jia-Fang Chung, Yung-Hsi Kao, Ching-Feng Cheng
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	activating transcription factor 3 inducer anti-obesity adipocyte adipogenesis lipolysis browning Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/2e576754604e4ea9a5a2f0ba3cffd417
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spelling	oai:doaj.org-article:2e576754604e4ea9a5a2f0ba3cffd4172021-11-28T04:28:09ZThe ATF3 inducer protects against diet-induced obesity via suppressing adipocyte adipogenesis and promoting lipolysis and browning0753-332210.1016/j.biopha.2021.112440https://doaj.org/article/2e576754604e4ea9a5a2f0ba3cffd4172022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221012269https://doaj.org/toc/0753-3322In this study, we investigated whether the activating transcription factor 3 (ATF3) inducer ST32db, a synthetic compound with a chemical structure similar to that of native Danshen compounds, exerts an anti-obesity effect in 3T3-L1 white preadipocytes, D16 beige cells, and mice with obesity induced by a high-fat diet (HFD). The results showed that ST32db inhibited 3T3-L1 preadipocyte differentiation by inhibiting adipogenesis/lipogenesis-related gene (and protein levels) and enhancing lipolysis-related gene (and protein levels) via the activation of β3-adrenoceptor (β3-AR)/PKA/p38, AMPK, and ERK pathways. Furthermore, ST32db inhibited triacylglycerol accumulation in D16 adipocytes by suppressing adipogenesis/lipogenesis-related gene (and protein levels) and upregulating browning gene expression by suppressing the β3-AR/PKA/p38, and AMPK pathways. Intraperitoneally injected ST32db (1 mg kg−1 twice weekly) inhibited body weight gain and reduced the weight of inguinal white adipose tissue (iWAT), epididymal WAT (eWAT), and mesenteric WAT, with no effects on food intake by the obese mice. The adipocyte diameter and area of iWAT and eWAT were decreased in obese mice injected with ST32db compared with those administered only HFD. In addition, ST32db significantly suppressed adipogenesis and activated lipolysis, browning, mitochondrial oxidative phosphorylation, and β-oxidation-related pathways by suppressing the p38 pathway in the iWAT of the obese mice. These results indicated that the ATF3 inducer ST32db has therapeutic potential for reducing obesity.Hui-Chen KuTsai-Yun ChanJia-Fang ChungYung-Hsi KaoChing-Feng ChengElsevierarticleactivating transcription factor 3 induceranti-obesityadipocyteadipogenesislipolysisbrowningTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112440- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	activating transcription factor 3 inducer anti-obesity adipocyte adipogenesis lipolysis browning Therapeutics. Pharmacology RM1-950
spellingShingle	activating transcription factor 3 inducer anti-obesity adipocyte adipogenesis lipolysis browning Therapeutics. Pharmacology RM1-950 Hui-Chen Ku Tsai-Yun Chan Jia-Fang Chung Yung-Hsi Kao Ching-Feng Cheng The ATF3 inducer protects against diet-induced obesity via suppressing adipocyte adipogenesis and promoting lipolysis and browning
description	In this study, we investigated whether the activating transcription factor 3 (ATF3) inducer ST32db, a synthetic compound with a chemical structure similar to that of native Danshen compounds, exerts an anti-obesity effect in 3T3-L1 white preadipocytes, D16 beige cells, and mice with obesity induced by a high-fat diet (HFD). The results showed that ST32db inhibited 3T3-L1 preadipocyte differentiation by inhibiting adipogenesis/lipogenesis-related gene (and protein levels) and enhancing lipolysis-related gene (and protein levels) via the activation of β3-adrenoceptor (β3-AR)/PKA/p38, AMPK, and ERK pathways. Furthermore, ST32db inhibited triacylglycerol accumulation in D16 adipocytes by suppressing adipogenesis/lipogenesis-related gene (and protein levels) and upregulating browning gene expression by suppressing the β3-AR/PKA/p38, and AMPK pathways. Intraperitoneally injected ST32db (1 mg kg−1 twice weekly) inhibited body weight gain and reduced the weight of inguinal white adipose tissue (iWAT), epididymal WAT (eWAT), and mesenteric WAT, with no effects on food intake by the obese mice. The adipocyte diameter and area of iWAT and eWAT were decreased in obese mice injected with ST32db compared with those administered only HFD. In addition, ST32db significantly suppressed adipogenesis and activated lipolysis, browning, mitochondrial oxidative phosphorylation, and β-oxidation-related pathways by suppressing the p38 pathway in the iWAT of the obese mice. These results indicated that the ATF3 inducer ST32db has therapeutic potential for reducing obesity.
format	article
author	Hui-Chen Ku Tsai-Yun Chan Jia-Fang Chung Yung-Hsi Kao Ching-Feng Cheng
author_facet	Hui-Chen Ku Tsai-Yun Chan Jia-Fang Chung Yung-Hsi Kao Ching-Feng Cheng
author_sort	Hui-Chen Ku
title	The ATF3 inducer protects against diet-induced obesity via suppressing adipocyte adipogenesis and promoting lipolysis and browning
title_short	The ATF3 inducer protects against diet-induced obesity via suppressing adipocyte adipogenesis and promoting lipolysis and browning
title_full	The ATF3 inducer protects against diet-induced obesity via suppressing adipocyte adipogenesis and promoting lipolysis and browning
title_fullStr	The ATF3 inducer protects against diet-induced obesity via suppressing adipocyte adipogenesis and promoting lipolysis and browning
title_full_unstemmed	The ATF3 inducer protects against diet-induced obesity via suppressing adipocyte adipogenesis and promoting lipolysis and browning
title_sort	atf3 inducer protects against diet-induced obesity via suppressing adipocyte adipogenesis and promoting lipolysis and browning
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/2e576754604e4ea9a5a2f0ba3cffd417
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The ATF3 inducer protects against diet-induced obesity via suppressing adipocyte adipogenesis and promoting lipolysis and browning

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