Department of Smart Green Technology Engineering, Pukyong National University, Busan 48513, Republic of Korea.
Department of Food Science and Nutrition, Pukyong National University, Busan 48513, Republic of Korea.
Int J Mol Sci. 2024 Aug 6;25(16):8579. doi: 10.3390/ijms25168579.
Obesity is a complex health condition characterized by excessive adipose tissue accumulation, leading to significant metabolic disturbances such as insulin resistance and cardiovascular diseases. Fatty acid synthase (FAS), a key enzyme in lipogenesis, has been identified as a potential therapeutic target for obesity due to its role in adipocyte differentiation and lipid accumulation. This study employed a multidisciplinary approach involving in silico and in vitro analyses to investigate the anti-adipogenic properties of maclurin, a natural phenolic compound derived from . Using SwissDock software (ChEMBL version 23), we predicted protein interactions and demonstrated a high probability (95.6%) of maclurin targeting FAS, surpassing the interaction rates of established inhibitors like cerulenin. Docking simulations revealed maclurin's superior binding affinity to FAS, with a binding score of -7.3 kcal/mol compared to -6.7 kcal/mol for cerulenin. Subsequent in vitro assays confirmed these findings, with maclurin effectively inhibiting FAS activity in a concentration-dependent manner in 3T3-L1 adipocytes, without compromising cell viability. Furthermore, maclurin treatment resulted in significant reductions in lipid accumulation and the downregulated expression of critical adipogenic genes such as PPARγ, C/EBPα, and FAS, indicating the suppression of adipocyte differentiation. Maclurin shows potential as a novel FAS inhibitor with significant anti-adipogenic effects, offering a promising therapeutic avenue for the treatment and prevention of obesity.
肥胖是一种复杂的健康状况，其特征是脂肪组织过度积累，导致代谢紊乱，如胰岛素抵抗和心血管疾病。脂肪酸合酶（FAS）作为脂肪生成的关键酶，由于其在脂肪细胞分化和脂质积累中的作用，已被确定为肥胖的潜在治疗靶点。本研究采用了多学科方法，包括计算机模拟和体外分析，研究了从 中提取的天然酚类化合物 maclurin 的抗脂肪生成特性。我们使用 SwissDock 软件（ChEMBL 版本 23）预测了蛋白质相互作用，并证明了 maclurin 靶向 FAS 的可能性很高（95.6%），超过了 cerulenin 等已确立抑制剂的相互作用率。对接模拟显示 maclurin 与 FAS 的结合亲和力更高，结合评分为-7.3 kcal/mol，而 cerulenin 为-6.7 kcal/mol。随后的体外实验证实了这些发现，maclurin 可有效抑制 3T3-L1 脂肪细胞中 FAS 的活性，呈浓度依赖性，且不影响细胞活力。此外，maclurin 处理导致脂质积累显著减少和关键脂肪生成基因如 PPARγ、C/EBPα 和 FAS 的表达下调，表明脂肪细胞分化受到抑制。Maclurin 作为一种新型 FAS 抑制剂具有显著的抗脂肪生成作用，为肥胖的治疗和预防提供了一种有前途的治疗途径。
