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Anti-Obesity Natural Products Tested in Juvenile Zebrafish Obesogenic Tests and Mouse 3T3-L1 Adipogenesis Assays
Authors:Hiroko Nakayama  Kanae Hata  Izumi Matsuoka  Liqing Zang  Youngil Kim  Djongchi Chu  Lekh Raj Juneja  Norihiro Nishimura  Yasuhito Shimada
Institution:1.Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan; (H.N.); (K.H.); (I.M.); (L.Z.); (N.N.);2.Zebrafish Drug Screening Center, Mie University, Tsu 514-8507, Japan;3.Rohto Pharmaceutical Co., Ltd, Osaka 544-0012, Japan; (Y.K.); (D.C.); (L.R.J.);4.Department of Integrative Pharmacology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan;5.Department of Bioinformatics, Mie University Advanced Science Research Promotion Center, Tsu 514-8507, Japan
Abstract:(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 However, many anti-obesity drugs have been withdrawn from the market due to their adverse effects.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.
Keywords:drug discovery  diabetes  metabolic syndrome  screening
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