College of Animal Science and Technology, Guangxi University, Nanning, Guangxi 530004, China.
College of Animal Science and Technology, Guangxi University, Nanning, Guangxi 530004, China; Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, Guangxi University, Nanning 530004, Guangxi, China.
Cell Signal. 2024 Dec;124:111448. doi: 10.1016/j.cellsig.2024.111448. Epub 2024 Oct 4.
Excessive adipose accumulation is the primary cause of obesity. Resveratrol (RES), a natural polyphenolic compound, has garnered significant attention for its anti-obesity properties. However, the precise mechanisms by which RES influences fat deposition have not yet been explored. In this study, the aim was to identify the target proteins and associated pathways of RES in order to elucidate the mechanisms by which RES reduces fat deposition. In this study, mice were administered 400 mg/kg of RES via gavage for 12 weeks. We found that while 400 mg/kg RES had no impact on the growth of the mice, it significantly reduced the weight of various white adipose tissues, as well as the serum and liver concentrations of total cholesterol and triglycerides. Network pharmacology identified 15 potential targets of RES and highlighted the PI3K/AKT signaling pathway as a key pathway. Molecular docking and dynamic simulations suggested that ESR1 might be the target protein through which RES exerts its anti-fat deposition effects. In vitro experiments revealed that ESR1 promotes the proliferation and inhibits the differentiation of 3 T3-L1 adipocytes, and suppresses the PI3K/AKT signaling pathway. Silencing the ESR1 gene altered the ability of RES to inhibit cell differentiation via the PI3K/AKT pathway. Gene expression results in subcutaneous adipose tissue, epididymal fat tissue, and liver tissue of mice were consistent with observations in cells. In summary, RES reduces white fat deposition by directly targeting the ESR1 protein and inhibiting the PI3K/AKT signaling pathway. Our findings provide new insights into the potential use of RES in the prevention and treatment of obesity.
过量脂肪堆积是肥胖的主要原因。白藜芦醇（RES）是一种天然多酚化合物，因其具有抗肥胖特性而备受关注。然而，RES 影响脂肪沉积的确切机制尚未得到探索。在本研究中，旨在确定 RES 的靶蛋白及其相关途径，以阐明 RES 减少脂肪沉积的机制。在本研究中，通过灌胃给予小鼠 400mg/kg 的 RES 持续 12 周。我们发现，虽然 400mg/kg 的 RES 对小鼠的生长没有影响，但它显著降低了各种白色脂肪组织的重量，以及血清和肝脏中总胆固醇和甘油三酯的浓度。网络药理学鉴定了 15 个 RES 的潜在靶标，并强调了 PI3K/AKT 信号通路是一个关键通路。分子对接和动态模拟表明，ESR1 可能是 RES 发挥其抗脂肪沉积作用的靶蛋白。体外实验表明，ESR1 促进 3T3-L1 脂肪细胞的增殖并抑制其分化，并抑制 PI3K/AKT 信号通路。沉默 ESR1 基因改变了 RES 通过 PI3K/AKT 通路抑制细胞分化的能力。小鼠皮下脂肪组织、附睾脂肪组织和肝脏组织的基因表达结果与细胞观察结果一致。总之，RES 通过直接靶向 ESR1 蛋白并抑制 PI3K/AKT 信号通路来减少白色脂肪沉积。我们的研究结果为 RES 在肥胖的预防和治疗中的潜在应用提供了新的见解。
