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Fetal Origins of Life Stage Disease: A Zebrafish Model for the Obesity Epidemic
Citation:
Angrish, M., S. Padilla, B. Chorley, AND A. Tennant. Fetal Origins of Life Stage Disease: A Zebrafish Model for the Obesity Epidemic. EMGS Annual Meeting 2016, Kansas City, MO, September 24 - 28, 2016.
Impact/Purpose:
Chemical exposure during key developmental windows may impact life-stage fat mass. Specifically, fetal obesogen exposure may shift multipotent stromal stem cell differentiation disproportionately toward the adipocyte pool. It is hypothesize that this chemical disruption of adipocyte organogenesis increases the number and size of fat depots later in life, leaving offspring more susceptible to life-stage obesity. yet the EPA has no chemical evaluation tool for this outcome. This work would provide EPA with a fast, reproducible, and higher throughput method that interrogates all of biology in a single assay. Specifically, this cutting edge method interrogates bioactivity using a full systems approach, in a model with complete metabolic activity, and at a time when the full signaling repertoire is expressed and active, to optimally examine how chemical dose and duration impact life-stage obesity.
Description:
In the U.S., childhood obesity has more than doubled in children and quadrupled in adolescents in the past 30 years, affects 35% of adults, and costs the U.S. healthcare industry >$200 billion annually. The chemical environment in the womb may cause susceptibility to different life-stage and life-long metabolic diseases including obesity. The challenge is to understand if exposures during developmentally sensitive windows impact life-stage disease, such as obesity, by increasing adipose tissue mass. In vitro models lack the integrated systems approach needed to assess adipose development, while mammalian models are impractical in a screen of thousands of chemicals. Therefore, an obesogen screening method was developed to interrogate bioactivity using a full systems approach, in a vertebrate zebrafish model with complete metabolic activity, at a time when the full signaling repertoire is expressed and active, to optimally examine how chemical dose and duration impact life-stage adipose mass. A time-line for adipose depot formation was mapped in zebrafish 6−14 days post fertilization (dpf) using the lipophilic dye, Nile Red, in combination with fluorescent microscopy. Those time points were then used to investigate the impact of embryonic tributyltin chloride (TBT, a known obesogen) exposure (10nM daily renewal, 0−5dpf) on adipose mass. Fluorescent microscopy revealed adipose depots that were larger and appeared 2 days earlier in TBT treated compared to controls. These results suggest the zebrafish model as a promising new tool to screen for chemical obesogens. This abstract may not necessarily reflect official Agency policy.