Abstract
The Mediterranean diet, rich in olive oil, is beneficial, reducing the risk of cardiovascular diseases and cancer. Olive oil is mostly composed of the monounsaturated fatty acid omega-9. We showed omega-9 protects septic mice modulating lipid metabolism. Sepsis is initiated by the host response to infection with organ damage, increased plasma free fatty acids, high levels of cortisol, massive cytokine production, leukocyte activation, and endothelial dysfunction. We aimed to analyze the effect of omega-9 supplementation on corticosteroid unbalance, inflammation, bacterial elimination, and peroxisome proliferator-activated receptor (PPAR) gamma expression, an omega-9 receptor and inflammatory modulator. We treated mice for 14 days with omega-9 and induced sepsis by cecal ligation and puncture (CLP). We measured systemic corticosterone levels, cytokine production, leukocyte and bacterial counts in the peritoneum, and the expression of PPAR gamma in both liver and adipose tissues during experimental sepsis. We further studied omega-9 effects on leukocyte rolling in mouse cremaster muscle-inflamed postcapillary venules and in the cerebral microcirculation of septic mice. Here, we demonstrate that omega-9 treatment is associated with increased levels of the anti-inflammatory cytokine IL-10 and decreased levels of the proinflammatory cytokines TNF-α and IL-1β in peritoneal lavage fluid of mice with sepsis. Omega-9 treatment also decreased systemic corticosterone levels. Neutrophil migration from circulation to the peritoneal cavity and leukocyte rolling on the endothelium were decreased by omega-9 treatment. Omega-9 also decreased bacterial load in the peritoneal lavage and restored liver and adipose tissue PPAR gamma expression in septic animals. Our data suggest a beneficial anti-inflammatory role of omega-9 in sepsis, mitigating leukocyte rolling and leukocyte influx, balancing cytokine production, and controlling bacterial growth possibly through a PPAR gamma expression-dependent mechanism. The significant reduction of inflammation detected after omega-9 enteral injection can further contribute to the already known beneficial properties facilitated by unsaturated fatty acid-enriched diets.
Highlights
Sepsis is a cause of morbidity and mortality in intensive care units and associated with increased hospital-related costs [1, 2]
We have previously shown that mice fed with chow rich in olive oil had increased survival rates, decreased neutrophil accumulation, lowered plasma tumor necrosis factor-α (TNF-α), prostaglandin E2, and leukotriene B4 levels in the peritoneal cavity after LPS-induced endotoxic shock [11]
We showed that omega-9 decreased nonesterified fatty acids in mice after enteric injection [18] and pretreatment with omega-9 improved lipid metabolism acting on peroxisome proliferator-activated receptor (PPAR) target genes with increasing survival of septic mice [19]
Summary
Sepsis is a cause of morbidity and mortality in intensive care units and associated with increased hospital-related costs [1, 2]. According to the Third International Consensus definitions, sepsis is a life-threatening organ dysfunction caused by unbalanced host response to infection [3]. The Mediterranean diet, characterized by high ingestion of olive oil, is associated to a reduction in the mortality of vascular diseases and cancer [6,7,8]. We have previously shown that mice fed with chow rich in olive oil had increased survival rates, decreased neutrophil accumulation, lowered plasma TNF-α, prostaglandin E2, and leukotriene B4 levels in the peritoneal cavity after LPS-induced endotoxic shock [11]
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