Farnesoid X receptor regulates PI3K/AKT/mTOR signaling pathway, lipid metabolism, and immune response in hybrid grouper.

Abstract

Some diseases related to lipid metabolism increase yearly in cultured fish, and the farnesoid X receptor (FXR) is a nuclear protein that plays a key role in inflammatory responses and lipid metabolism. However, the roles of FXR in hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂) remain poorly understood. The main objective of this study was to explore the roles of hepatic FXR in triggering the immune response and the potential functions of FXR in regulating the lipid metabolism. In the present study, the full-length sequence of fxr from hybrid grouper was cloned and characterized for the first time. Upon the Vibrio parahaemolyticus stimulation, the transcriptional level of fxr was rapidly elevated in the head kidney tissue in the early stage of infection. In vivo and vitro, activation of FXR by obeticholic acid (OA) significantly increased the concentrations and mRNA levels of hepatic inflammatory cytokines. These effects were inversed when FXR was inhibited by guggulsterone (GU). Moreover, the activation of FXR to suppress the PI3K/AKT/mTOR signaling pathway improves hepatic lipid metabolism and reduces hepatic lipid accumulation in vivo and vitro. In addition, the inhibition of FXR activated the PI3K/AKT/mTOR pathway, decreased the lipolysis and increased the lipogenesis, and subsequently increased the lipid accumulation in fish. These results revealed the positive roles of FXR in triggering immune responses and improving lipid metabolism and accumulation in hybrid grouper.