Protective effects of n‐6 fatty acids‐enriched diet on intestinal ischaemia/reperfusion injury involve lipoxin A₄ and its receptor

Abstract

BACKGROUND AND PURPOSELong-term intake of dietary fatty acids is known to predispose to chronic inflammation, but their effects on acute intestinal ischaemia/reperfusion (I/R) injury is unknown. The aim of this study was to determine the consequences of a diet rich in n-3 or n-6 polyunsaturated fatty acids (PUFA) on intestinal I/R-induced damage. EXPERIMENTAL APPROACHMice were fed three different isocaloric diets: a balanced diet used as a control and two different PUFA-enriched diets, providing either high levels of n-3 or of n-6 PUFA. Intestinal injury was evaluated after intestinal I/R. PUFA metabolites were quantitated in intestinal tissues by LC-MS/MS. KEY RESULTSIn control diet-fed mice, intestinal I/R caused inflammation and increased COX and lipoxygenase-derived metabolites compared with sham-operated animals. Lipoxin A4 (LxA4) was significantly and selectively increased after ischaemia. Animals fed a high n-3 diet did not display a different inflammatory profile following intestinal I/R compared with control diet-fed animals. In contrast, intestinal inflammation was decreased in the I/R group fed with high n-6 diet and level of LxA4 was increased post-ischaemia compared with control diet-fed mice. Blockade of the LxA4 receptor (Fpr2), prevented the anti-inflammatory effects associated with the n-6 rich diet. CONCLUSIONS AND IMPLICATIONSThis study indicates that high levels of dietary n-6, but not n-3, PUFAs provides significant protection against intestinal I/R-induced damage and demonstrates that the endogenous production of LxA4 can be influenced by diet. 6kPGF1α, 7(S) Abbreviations

Formyl peptide receptor 1 suppresses gastric cancer angiogenesis and growth by exploiting inflammation resolution pathways

“…ALOXs and GPR32 are required for FPR1-mediated anti-angiogenic activity in GC cells. Consistently, administration of v-3 or v-6 PUFA-enriched diets, which enforces endogenous production of SPMs, 9 inhibited xenograft growth of FPR1-silenced GC cells by ablating their angiogenic activity. Our data indicate that FPR1 signaling activates a pro-resolving program in GC cells that inhibits angiogenesis and growth.…”

Effects of n-3 PUFAs on Intestinal Mucosa Innate Immunity and Intestinal Microbiota in Mice after Hemorrhagic Shock Resuscitation

“…Some studies reported that arachidonic acid, one of n -6 PUFAs, was not only a precursor of pro-inflammatory bioactive lipids, but also a member of the potent anti-inflammatory mediators known as lipoxins [36,37,38,39,40]. Several reports have indicated a protective role for lipoxins or stable lipoxin analogues in ischemia-reperfusion [41,42,43]. Gobbetti et al (2015) reported that high levels of dietary n -6 PUFAs, but not n -3 PUFAs, provided significant protection against IRI.…”

“…Gobbetti et al (2015) reported that high levels of dietary n -6 PUFAs, but not n -3 PUFAs, provided significant protection against IRI. In that study, nine weeks of dietary PUFA intake were found to directly influence the intestinal microbial communities, and the subsequent formation of bacterial metabolites might play important roles in this process [41]. In addition, n -3 and n -6 PUFAs are natural ligands of the G-protein coupled receptor 120, which has been demonstrated to inhibit NF-κB signaling upon binding to Toll-like receptor 4 in macrophages and adipocytes [44,45].…”

Special pro-resolving mediator (SPM) actions in regulating gastro-intestinal inflammation and gut mucosal immune responses

“…However, the clinical data has not been as clear as the experimental data. Experimental data shows promise as diets supplemented with omega-6 fatty acids increase LXA 4 production and attenuation of inflammatory injury (Gobbetti et al, 2015). Systemic treatment with D-series resolvins improves disease activity score with reduced colonic damage and decreased PMN infiltration in murine colitis models (Bento et al, 2011).…”