Zebrafish obesogenic test: a tool for screening molecules that target adiposity

Area of Science:

• Endocrinology
• Toxicology
• Aquatic Biology

Background:

• Dietary and environmental factors can disrupt endocrine signaling and lipid metabolism, contributing to obesity.
• Existing research methods for obesity assessment include in vitro assays and rodent models.
• There is a need for intermediate, whole-organism assays to evaluate obesogenic compounds.

Purpose of the Study:

• To introduce and validate the zebrafish obesogenic (ZO) test, a novel short-term assay for assessing obesogenic and anti-obesogenic compounds.
• To evaluate the efficacy of the ZO test in identifying environmental toxicants and pharmaceutical compounds that affect white adipose tissue (WAT) dynamics.
• To establish the ZO test as a valuable tool for environmental and human risk assessment.

Main Methods:

• The zebrafish obesogenic (ZO) test utilizes live zebrafish larvae and the Nile Red (NR) fluorescent probe to visualize and quantify adipocyte lipid droplets.
• The assay assesses white adipose tissue (WAT) dynamics and overall adiposity in response to various compounds, including environmental contaminants and drugs.
• Larvae were exposed to environmentally relevant concentrations of tributyltin chloride (TBT) and other known obesogenic or anti-obesogenic compounds.

Main Results:

• Zebrafish larvae exposed to tributyltin chloride (TBT) showed a significant increase in adiposity, regardless of dietary lipid content.
• The ZO test successfully classified known obesogenic compounds (e.g., rosiglitazone, TBT) and anti-obesogenic compounds.
• The assay demonstrated sensitivity to compounds affecting adiposity in a manner consistent with their known effects in other models.

Conclusions:

• The zebrafish obesogenic (ZO) test is a validated whole-organism assay for screening obesogenic and anti-obesogenic compounds.
• The ZO test provides a valuable intermediate step between in vitro and rodent assays for obesity research.
• This assay offers relevant data for assessing the risks of environmental toxicants and pharmaceutical compounds to both aquatic species and humans.