Differential tissue regulation of peroxisome proliferator-activated receptor α (PPARα) and cannabinoid receptor 1 (CB1) gene transcription pathways by diethylene glycol dibenzoate (DEGB): preliminary observations in a seabream (Sparus aurata) in vivo mo

- The predicted Kd value of DEGB for seabream PPARα is in the submicromolar range.
- Fish exposed 100 μgL−1 of DEGB showed increased hepatic PPARα but not CB1 mRNAs.
- DEGB 100 μgL−1 upregulated CB1, SREBP-1c, LXRα, and NPY expression in the brain.
- The highest concentration of DEGB reduced plasma levels of TG and LDL.
- In the liver, DEGB acts as PPARα agonist downregulating endocannabinoid signaling.

Today a variety of endocrine disrupting chemicals (EDCs) are recognized in the group of metabolic disruptors, a wide range of environmental contaminants that alter energy balance regulation by affecting the peroxisome proliferator-activated receptor (PPAR)/retinoid X receptor (RXR) pathway. Herein, we investigated the effect of diethylene glycol dibenzoate (DEGB), a dibenzoate-based plasticizer used as alternative to phthalates, on the expression of key genes involved in lipid metabolism and energy balance by using Sparus aurata juveniles as models. We also evaluated the correlation between cannabinoid receptor 1 (CB1) and PPARα transcriptional patterns in both liver and brain tissues. Exposure to the highest DEGB concentration differentially modulated PPARα/CB1 transcriptional pathways in liver/brain tissues of seabream. We hypothesize that, at peripheral level (i.e. liver), DEGB acts as PPARα agonist resulting in a potential stimulation of key lipolytic genes and a concomitant down-regulation of endocannabinoid metabolic enzyme genes.