期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 145, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2021.112440
关键词
activating transcription factor 3 inducer; anti-obesity; adipocyte; adipogenesis; lipolysis; browning
资金
- Ministry of Science and Technology, Taiwan [MoST 107-2314-B-303-015-MY3]
- Tzu Chi General Hospital, Taiwan [TCMMP108-04-02]
- Academia Sinica, Taiwan [TCAS-108-01]
- Tzu Chi, Taiwan [TCAS-108-01]
The study found that the ATF3 inducer ST32db effectively reduced obesity by inhibiting adipogenesis, activating lipolysis and browning pathways, and reducing fat accumulation in adipocytes. This suggests the therapeutic potential of ST32db in combating obesity.
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 beta 3-adrenoceptor (beta 3-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 beta 3-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 beta-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.
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