DHA-Enriched Phospholipids and EPA-Enriched Phospholipids Alleviate Lipopolysaccharide-Induced Intestinal Barrier Injury in Mice via a Sirtuin 1-Dependent Mechanism.

Abstract

Intestinal barrier dysfunction has emerged as a potential contributor to the development of several severe diseases. Herein, the effect and underlying mechanism of DHA-enriched phospholipids (DHA-PL) and EPA-enriched phospholipids (EPA-PL) on protecting against lipopolysaccharide (LPS)-induced intestinal barrier injury were elucidated. C57BL/6J male mice were fed an AIN-93G diet containing 1% DHA-PL or EPA-PL for 4 weeks and then were intraperitoneally injected with LPS (10 mg/kg) to cause intestinal barrier injury. The results manifested that DHA-PL and EPA-PL pretreatment balanced apoptosis and autophagy in intestinal epithelial cells and maintained intestinal tight junction integrity. Our findings also demonstrated that cotreatment with EX-527, a sirtuin 1 specific inhibitor, hindered the role of DHA-PL and EPA-PL against LPS-evoked intestinal barrier injury through reversing the inhibitory action of them on NF-κB and MAPKs activation as well as their potentiating actions on Nrf2 nuclear translocation. Overall, DHA-PL and EPA-PL alleviated LPS-mediated intestinal barrier injury via inactivation of the NF-κB and MAPKs pathways as well as activating the Nrf2 antioxidant pathway via up-regulating sirtuin 1.