GW9662 , a Peroxisome proliferator-activated receptor ? (PPAR?) inhibitor, impairs early embryonic development in zebrafish

Peroxisome proliferator-activated receptor ? (PPAR?) functions as a nuclear transcription factor with primary roles in lipid and glucose metabolism and adipocyte differentiation. Despite intensive research in metabolic contexts, its role during early vertebrate development remains underexplored. Our study focused on understanding PPAR?'s developmental role by administering a PPAR? antagonist called GW9662 (GW) to block its activity in zebrafish embryos during early development from 6 hours post-fertilization (hpf) to 24 hpf. The first phenotypic screening found that ventralization occurred along with an expanded blood island region, a structure that is involved in early blood cell development. Transcriptomic analysis demonstrated that exposure to GW led to dysregulation of multiple biological pathways, including cytoskeletal organization, lipid biosynthesis, and epithelial-to-mesenchymal transition (EMT). Immunohistochemistry further validated these findings, demonstrating increased lipid accumulation, cytoskeletal disruption, and altered EMT markers. Our findings suggest that PPAR? plays a crucial role in multiple processes during early embryogenesis, and this disruption can lead to profound morphological and molecular alterations. Overall design: Zebrafish embryos were exposed to GW-9662, followed by phenotyping, RNA seq, immunohistochemistry and Nile Red stain