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An Embryonic Zebrafish Screening Method for Early Life-stage Obesity
Citation:
Angrish, M., P. Cagle, S. Padilla, A. Tennant, J. Hedge, B. Chorley, AND T. Tal. An Embryonic Zebrafish Screening Method for Early Life-stage Obesity. NC SOT Annual Meeting, Research Triangle Par, NC, October 25, 2016.
Impact/Purpose:
This work describes a method to test if environmental exposure during development affects adipose mass later in life with an appropriate systems biology-based method.
Description:
An Embryonic Zebrafish Screening Method for Early Life-stage ObesityMM Angrish†, P Cagle‡, S Padilla†, AH Tennant†, J Hedge†, B Chorley†, T Tal†,† National Health and Environmental Effects Research Laboratory, ORD, US EPA, RTP, NC27709Research Triangle Park, North Carolina 27709, United States‡ North Carolina Agricultural and Technical State University, Department of Energy and Environmental Systems/Biology, Greensboro, North Carolina 27411, United States AbstractThe chemical environment in the womb may increase susceptibility to different life-stage and life-long metabolic diseases including obesity. Specifically, evidence suggests fetal obesogen exposure may shift multipotent stromal stem cell differentiation disproportionately toward the adipocyte pool. This chemical disruption of adipocyte organogenesis may increase the number and size of fat depots later in life, rendering offspring more susceptible to obesity. The challenge is to understand if environmental chemical exposures during developmentally sensitive windows affect adipose mass later in life. 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 optimal zebrafish obesogen screening method was developed to examine the effect of embryonic chemical exposure on 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 and gene expression. Those time points were then used to evaluate embryonic tributyltin chloride (TBT, a known obesogen) exposure on adipose mass. Embryos exposed to TBT (10nM daily renewal, 0−5 dpf) had increased adipogenic and early commitment markers PPARγ, Cidec, and Znf423 (1.8-, 1.6 and 3.2-fold, respectively; p <0.05), and developed adipose depots that were larger (3.7-fold at 10 dpf, p =0.0255) and appeared 2 days earlier (8 dpf versus 10 dpf) than 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.