DHA and its derived lipid mediators MaR1, RvD1 and RvD2 block TNF-alpha inhibition of intestinal sugar and glutamine uptake in Caco-2 cells
Tumor necrosis factor-alfa (TNF-alpha) is a pro-inflammatory cytokine highly-involved in intestinal inflammation. Omega-3 polyunsaturated fatty acids (n3-PUFAs) show anti-inflammatory actions. We previously demonstrated that the n3-PUFA EPA prevents TNF-alpha inhibition of sugar uptake in Caco-2 cells. Here, we investigated whether the n3-PUFA DHA and its derived specialized pro-resolving lipid mediators (SPMs) MaR1, RvD1 and RvD2, could block TNF-alpha inhibition of intestinal sugar and glutamine uptake. DHA blocked TNF-alpha-induced inhibition of alpha-methyl-D-glucose (alpha MG) uptake and SGLT1 expression in the apical membrane of Caco-2 cells, through a pathway independent of GPR120. SPMs showed the same preventive effect but acting at concentrations 1000 times lower. In diet-induced obese (DIO) mice, oral gavage of MaR1 reversed the up-regulation of pro-inflammatory cytokines found in intestinal mucosa of these mice. However, MaR1 treatment was not able to counteract the reduced intestinal transport of alpha MG and SGLT1 expression in the DIO mice. In Caco-2 cells, TNF-alpha also inhibited glutamine uptake being this inhibition prevented by EPA, DHA and the DHA-derived SPMs. Interestingly, TNF-alpha increased the expression in the apical membrane of the glutamine transporter B(0)AT1. This increase was partially blocked by the n-3 PUFAs. These data reveal DHA and its SPMs as promising biomolecules to restore intestinal nutrients transport during intestinal inflammation. (C) 2019 Elsevier Inc. All rights reserved.