ゼブラフィッシュ稚魚を用いた内臓脂肪評価スクリーニング技術

• Published in: 日本薬理学会年会要旨集 p. 2-B-O01-3
• Main Authors: 幡, 佳苗, 塚本, 恒星, 中山, 寛子, 深田, 一剛, 西村, 訓弘, 熊沢, 益徳, 臧, 黎清, 湯浅, 翔平, 勝崎, 裕隆, 島田, 康人, 松岡, いづみ
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: adipocyte; adipose tissue; lipid metabolism; toxicity
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.96.0_2-B-O01-3

[Background] The obesity epidemic has been drastically progressing in both children and adults worldwide. Pharmacotherapy is considered necessary for its treatment. Because many anti-obesity drugs have been withdrawn from the market due to their adverse effects, the development of new drugs is still needed. Zebrafish are ideal model animals for in vivo testing of anti-obesity compounds, and disease models of several types of obesity have been developed.[Methods] We developed a screening system using young zebrafish, "zebrafish obesogenic test (ZOT)", and performed screening using the focused natural product (NP) library. We then performed anti-adipogenic testing using the mouse 3T3-L1 preadipocytes to make comparison with ZOT outputs.[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 (GD), green tea extract (GTE), red pepper extract, nobiletin, and Moringa (MO) leaf powder) exerted anti-obesity effects in diet-induced obese adult zebrafish, as a conventional model (Nakayama H, et al., Molecules. 2020;25:5840). In addition, we validated that GD improved visceral adiposity in high-fat fed mice through UCP1 upregulation (Zang L, et al., Front Nutr. 2021;8:650975). Based on the ZOT techniques, we further analyzed the gene expression profiles of the adipose tissue in GTE-fed zebrafish (Zang L, et al., Molecules. 2021;26:2627) and tried to discover bioactive compounds in MO leaf using ZOT (Mastuoka I, et al., Food Sci Nurt. 2022;00:1-9.).[Conclusion] ZOT can be a high-throughput alternative to adult zebrafish models and can be applied for in vivo screening to discover novel therapeutics for visceral obesity and potentially also other metabolic disorders.