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.

在本研究中，我们研究了激活转录因子 3 (ATF3) 诱导剂 ST32db（一种化学结构与天然丹参化合物相似的合成化合物）是否在 3T3-L1 白色前脂肪细胞、D16 米色细胞、以及由高脂肪饮食（HFD）引起的肥胖小鼠。结果表明，ST32db通过抑制脂肪生成/脂肪生成相关基因（和蛋白质水平）并通过激活β3-肾上腺素受体（β3-AR）/PKA/增强脂肪分解相关基因（和蛋白质水平）来抑制3T3-L1前脂肪细胞分化。 p38、AMPK 和 ERK 通路。此外，ST32db 通过抑制脂肪生成/脂肪生成相关基因（和蛋白质水平）来抑制 D16 脂肪细胞中三酰甘油的积累，并通过抑制 β3-AR/PKA/p38 和 AMPK 途径上调褐变基因表达。腹腔注射 ST32db（1 mg kg ^-1每周两次）可抑制体重增加，并减少腹股沟白色脂肪组织 (iWAT)、附睾 WAT (eWAT) 和肠系膜 WAT 的重量，但对肥胖小鼠的食物摄入没有影响。与仅注射 HFD 的肥胖小鼠相比，注射 ST32db 的肥胖小鼠的脂肪细胞直径和 iWAT 和 eWAT 面积有所减少。此外，ST32db 通过抑制肥胖小鼠 iWAT 中的 p38 途径，显着抑制脂肪生成并激活脂肪分解、褐变、线粒体氧化磷酸化和 β-氧化相关途径。这些结果表明 ATF3 诱导剂 ST32db 具有减少肥胖的治疗潜力。