Plant sterol ester of α-linolenic acid improves NAFLD through modulating gut microbiota and attenuating lipopolysaccharide-induced inflammation via regulating TLR4/NF-κB signaling pathway

Abstract

Lipopolysaccharide (LPS) originating from dysbiotic gut microbiota is regarded as a critical mediator for triggering the inflammation responsible for non-alcoholic fatty liver disease (NAFLD). The preventive effect of plant sterol ester of α-linolenic acid (PS-ALA) on NAFLD was identified in our previous research, yet, the mechanisms linking this effect to gut microbiota and LPS-triggered inflammation remain unclear. In present study, we found that PS-ALA treatment could counteract gut microbial dysbiosis and maintain intestinal barrier function. These beneficial effects of PS-ALA reduced bacterial LPS production and leakage into the portal circulation which attenuated LPS-triggered hepatic inflammation. In addition, PS-ALA inhibited LPS-triggered TLR4/NF-κB signaling pathway activation and reduced pro-inflammatory cytokines release in HepG2 cells. In conclusion, PS-ALA has a dual inhibition effect on endotoxin, including reducing LPS production in the gut and blocking the activation of the LPS-induced TLR4/NF-κB signaling pathway, thereby mitigating inflammatory reactions in the liver and preventing NAFLD.

Keywords

• Plant sterol ester of α-linolenic acid
• Gut microbiota
• Nonalcoholic fatty liver disease
• Lipopolysaccharide
• TLR4