Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan.
Zebrafish Drug Screening Center, Mie University, Tsu 514-8507, Japan.
Molecules. 2020 Dec 10;25(24):5840. doi: 10.3390/molecules25245840.
(1) Background: The obesity epidemic has been drastically progressing in both children and adults worldwide. Pharmacotherapy is considered necessary for its treatment. However, many anti-obesity drugs have been withdrawn from the market due to their adverse effects. Instead, natural products (NPs) have been studied as a source for drug discovery for obesity, with the goal of limiting the adverse effects. Zebrafish are ideal model animals for in vivo testing of anti-obesity NPs, and disease models of several types of obesity have been developed. However, the evidence for zebrafish as an anti-obesity drug screening model are still limited. (2) Methods: We performed anti-adipogenic testing using the juvenile zebrafish obesogenic test (ZOT) and mouse 3T3-L1 preadipocytes using the focused NP library containing 38 NPs and compared their results. (3) Results: Seven and eleven NPs reduced lipid accumulation in zebrafish visceral fat tissues and mouse adipocytes, respectively. Of these, five NPs suppressed lipid accumulation in both zebrafish and 3T3-L1 adipocytes. We confirmed that these five NPs (globin-digested peptides, green tea extract, red pepper extract, nobiletin, and Moringa leaf powder) exerted anti-obesity effects in diet-induced obese adult zebrafish. (4) Conclusions: ZOT using juvenile fish can be a high-throughput alternative to ZOT using adult zebrafish and can be applied for in vivo screening to discover novel therapeutics for visceral obesity and potentially also other disorders.
(1) 背景:肥胖症在全球范围内的儿童和成年人中都呈急剧上升趋势。药物治疗被认为是必要的。然而,由于其副作用,许多减肥药已被撤出市场。相反,天然产物(NPs)已被研究作为肥胖症药物发现的来源,目的是限制副作用。斑马鱼是用于体内抗肥胖 NP 测试的理想模型动物,并且已经开发出几种类型肥胖症的疾病模型。然而,斑马鱼作为抗肥胖药物筛选模型的证据仍然有限。(2) 方法:我们使用幼鱼肥胖斑马鱼测试(ZOT)和含 38 种 NPs 的聚焦 NP 文库对小鼠 3T3-L1 前脂肪细胞进行抗脂肪生成测试,并比较了它们的结果。(3) 结果:七种和十一种 NPs 分别减少了斑马鱼内脏脂肪组织和小鼠脂肪细胞中的脂质积累。其中,五种 NPs 抑制了斑马鱼和 3T3-L1 脂肪细胞中的脂质积累。我们证实,这五种 NPs(球蛋白消化肽、绿茶提取物、红辣椒提取物、川陈皮素和辣木叶粉)在饮食诱导的肥胖成年斑马鱼中发挥了抗肥胖作用。(4) 结论:使用幼鱼的 ZOT 可以替代使用成年斑马鱼的 ZOT,并且可以用于体内筛选,以发现治疗内脏肥胖症和潜在其他疾病的新疗法。