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 However, many anti-obesity drugs have been withdrawn from the market due to their adverse effects.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.
Highlights
Especially abdominal obesity, which is characterized by increased visceral adipose tissue (VAT), has been distinctly linked to metabolic diseases including hepatosteatosis, type 2 diabetes mellitus (T2DM), atherosclerosis, cardiovascular diseases, and several types of cancers
The Nile Red (NR)-stained visceral adipose tissue (VAT; red color) was significantly (p < 0.01) increased in zebrafish fed a high-fat diet feeding (HFD) compared to those fed a normal diet (ND; Figure 1b), as shown previously [16]
Nine natural products (NPs) showed toxicity, so we administered them at a lower concentration of 10 μg/mL
Summary
Especially abdominal obesity, which is characterized by increased visceral adipose tissue (VAT), has been distinctly linked to metabolic diseases including hepatosteatosis, type 2 diabetes mellitus (T2DM), atherosclerosis, cardiovascular diseases, and several types of cancers. Pharmacological management is more effective than diet or exercise therapy, many drugs are not approved or have been withdrawn from the market because of their adverse effects such as the CB1 receptor agonist rimonabant, which imposed a heightened risk of psychiatric diseases [3,4]. For this reason, a variety of natural products (NPs) and their constituents are being tested to ameliorate visceral obesity with minimal side effects [5]. Because obesity is a complex and systemic disease, in vitro results are not always translatable to clinical situations with respect to drug efficacy, drug delivery, absorption, pharmacokinetics, and side effects
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