Examining the responses of the zebrafish (Danio rerio) gastrointestinal system to the suspected obesogen diethylhexyl phthalate.

Epidemiological evidence suggests that phthalate plasticizers may act as "obesogens", which are chemicals that exacerbate obesity. The gastrointestinal (GI) system is the primary exposure route for phthalates, however, the relationship between phthalate-driven perturbations of GI system functions that can influence obesity has yet to be examined. To address this knowledge gap, we exposed Danio rerio (zebrafish) for 60 days to either (1) Control feeding (5 mg/fish/day), (2) Overfeeding (20 mg/fish/day) or (3) Overfeeding with diethyl-hexyl phthalate (DEHP) (20 mg/fish/day with 3 mg/kg DEHP). After 60 days, Overfed and Overfed + DEHP zebrafish had elevated body mass, and hepatosomatic and gonadosomatic indices. RNAseq analysis of the GI revealed enrichment of gene networks related to lipid metabolism in the Overfed + DEHP group. Many of the enriched networks were under transcriptional control of peroxisome proliferator activated receptor alpha (pparα), a known modulator of lipid metabolism, immune function, and GI function. confirmed that pparα was overexpressed in the Overfed + DEHP zebrafish, further revealing a pathway by which DEHP may influence lipid metabolism via the GI. These data increase our understanding of phthalate-driven effects on GI function and lipid metabolism, identifying gut-specific gene networks that may drive phthalate-exacerbated obesity.

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