linoleic-acid and Sepsis

Fatty acid composition in the Western diet has shifted from saturated to polyunsaturated fatty acids (PUFAs), and specifically to linoleic acid (LA, 18:2), which has gradually increased in the diet over the past 50 y to become the most abundant dietary fatty acid in human adipose tissue. PUFA-derived oxylipins regulate a variety of biological functions. The cytochrome P450 (CYP450)–formed epoxy fatty acid metabolites of LA (EpOMEs) are hydrolyzed by the soluble epoxide hydrolase enzyme (sEH) to dihydroxyoctadecenoic acids (DiHOMEs). DiHOMEs are considered cardioprotective at low concentrations but at higher levels have been implicated as vascular permeability and cytotoxic agents and are associated with acute respiratory distress syndrome in severe COVID-19 patients. High EpOME levels have also correlated with sepsis-related fatalities; however, those studies failed to monitor DiHOME levels. Considering the overlap of burn pathophysiology with these pathologies, the role of DiHOMEs in the immune response to burn injury was investigated. 12,13-DiHOME was found to facilitate the maturation and activation of stimulated neutrophils, while impeding monocyte and macrophage functionality and cytokine generation. In addition, DiHOME serum concentrations were significantly elevated in burn-injured mice and these increases were ablated by administration of 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a sEH inhibitor. TPPU also reduced necrosis of innate and adaptive immune cells in burned mice, in a dose-dependent manner. The findings suggest DiHOMEs are a key driver of immune cell dysfunction in severe burn injury through hyperinflammatory neutrophilic and impaired monocytic actions, and inhibition of sEH might be a promising therapeutic strategy to mitigate deleterious outcomes in burn patients.

Topics: Animals; Burns; Epoxide Hydrolases; Humans; Immunity, Innate; Inflammation; Linoleic Acid; Mice; Mice, Inbred C57BL; Phenylurea Compounds; Piperidines; Sepsis

Soyabean oil-based emulsions high in linoleic acid used in parenteral nutrition (PN) could interfere with immune function and may increase the risk of septic complications. Olive oil-based emulsions, high in oleic acid, could have fewer immune effects. We compared the effects of a soyabean oil-based emulsion v. an olive oil-based emulsion on infection rate, appearance of new infection episodes, leucocyte count (peak and evolution), acute-phase proteins, and major health outcomes in intensive care unit (ICU) adult patients receiving PN. The study was designed as an observational, retrospective, single-centre, cohort study in a general ICU. Patients in the SOYA cohort (n 16) received a soyabean oil-based emulsion and patients in the OLIVE cohort (n 23), an olive oil-based emulsion. Both cohorts had similar basal characteristics and received a similar energy load. The SOYA cohort received an oleic acid:linoleic acid ratio of 0.43 and the OLIVE cohort 2.99 (P < 0.001). No differences were observed in infection rate and appearance, acute-phase proteins, and major health outcomes. At the end of PN, blood leucocyte count decreased by 3.25 x 109 cells/l in the SOYA cohort and increased by 4.51 x 109 cells/l in the OLIVE cohort from baseline values (P = 0.036). Peak leucocyte count presented a trend for a higher value in the OLIVE cohort v. the SOYA cohort (18.86 v. 15.28 x 109 cells/l; P = 0.078). The use of an olive oil-based emulsion in PN had no effect on infection, acute-phase proteins, major health outcomes, and presented higher leucocyte count at the end of PN and a trend to higher peak leucocyte count when compared with soyabean oil-based emulsion in ICU patients.

Topics: Acute-Phase Proteins; Critical Care; Fat Emulsions, Intravenous; Female; Hospital Mortality; Humans; Length of Stay; Leukocyte Count; Linoleic Acid; Male; Middle Aged; Oleic Acid; Olive Oil; Parenteral Nutrition, Total; Plant Oils; Retrospective Studies; Sepsis; Soybean Oil

In sepsis the utilization of endogenous and administered fuel sources is sometimes impaired. The precise origin of this metabolic failure is currently unknown. In long term and severe septic processes an increased peripheral energy deficit appears accompanied by a drastically augmented muscle protein catabolism. Branched chain amino acids released by this protein breakdown, at least temporarily, meet the energy needs of the muscles. Ketone bodies as energy source for the muscle are not available because their production is diminished in sepsis. The question of whether or not fat emulsions can be administered to septic patients still remains unanswered, although some recent investigations have demonstrated that fat is utilized and oxidized by septic patients. Results from our patients indicate that a marked reduction of cholesterin ester quotient, an increase of total and VLDL triglycerides and a severe reduction of HLDL Cholesterin are particularly characteristic changes in lipid metabolism during sepsis. The proportional decrease of the linoleic acid levels in cholesterol esters of plasma observed in septic patients was even more pronounced followed severe injury. Together with others we believe that parenteral fat application is not contraindicated in sepsis. The decision to infuse fat emulsions depends more on the metabolic situation of a patient than on a specific diagnosis; in other words, a sufficient peripheral oxygen supply, the level of the serum triglycerides and the reaction of the blood glucose concentration to an intravenously administered fat emulsion are, among others, the decisive factors.

Topics: Adult; Cholesterol; Cholesterol Esters; Energy Metabolism; Fat Emulsions, Intravenous; Humans; Linoleic Acid; Linoleic Acids; Lipoproteins; Liver; Male; Sepsis; Surgical Wound Infection; Triglycerides; Wounds and Injuries