Replacement of fish meal with full fat Hermetia illucens modulates hepatic FXR signaling in juvenile rainbow trout (Oncorhynchus mykiss): Exploring a potential role of ecdysteroids

The present study was conducted to investigate the effects of fish meal (FM) replacement with full fat <i>Hermetia illucens</i> (HI) on the molecular mechanisms regulating lipid and bile salt (BA) homeostasis in rainbow trout (<i>Oncorhynchus mykiss</i>) juveniles. We thus explore the presence of 20-hydroxyecdysone (20E) in an insect meal-based diet and evaluate its potential involvement in regulating the molecular mechanisms/basis of FXR:RXR axis signaling. Ecdysteroids are a category of steroid hormones which bind a nuclear-receptor complex composed of ecdysone receptor (EcR) and ultraspiracle protein (USP) and regulate insect molting and metamorphosis. In all vertebrates, including fish, EcR-USP homologs are the Farnesoid X receptors (FXR) and the Retinoid X receptors (RXR), which are known to regulate crucial physiological and metabolic aspects, including BA synthesis and cholesterol homeostasis. <i>In silico</i> prediction indicates that 20E binds the heterodimeric complex with a binding affinity constant K_d equals to 610 ± 60 nM and affects positively the dimerization process. Results also demonstrated the coordinated increased expression of FXR and RXR, as well as their downstream target genes (<i>i.e.</i> short heterodimer partner 1 and 2) in rainbow trout fed diets containing HI meal. This latter finding was paralleled by a significant down-regulation of CYP7a1 and CYP8b1 gene expression together with a decrease in hepatic total cholesterol, triglyceride, and BA levels. Overall, our study suggested that FXR is a potential target for 20E content in insect meal and provided preliminary data on the potential role of ecdysteroids in regulating the metabolic status of teleost fish through modulation of FXR signaling in the enterohepatic system.