The ω-3 Polyunsaturated Fatty Acids and Oxidative Stress in Long-Term Parenteral Nutrition Dependent Adult Patients: Functional Lipidomics Approach.

Omega-3 polyunsaturated fatty acids (ω-3PUFAs) are introduced into parenteral nutrition (PN) as hepatoprotective but may be susceptible to the lipid peroxidation while olive oil (OO) is declared more peroxidation resistant. We aimed to estimate how the lipid composition of PN mixture affects plasma and erythrocyte lipidome and the propensity of oxidative stress. A cross-sectional comparative study was performed in a cohort of adult patients who were long-term parenterally administered ω-3 PUFAs without (FO/-, n = 9) or with (FO/OO, n = 13) olive oil and healthy age- and sex-matched controls, (n = 30). Lipoperoxidation assessed as plasma and erythrocyte malondialdehyde content was increased in both FO/- and FO/OO groups but protein oxidative stress (protein carbonyls in plasma) and low redox status (GSH/GSSG in erythrocytes) was detected only in the FO/- subcohort. The lipidome of all subjects receiving ω-3 PUFAs was enriched with lipid species containing ω-3 PUFAs (FO/-˃FO/OO). Common characteristic of all PN-dependent patients was high content of fatty acyl-esters of hydroxy-fatty acids (FAHFAs) in plasma while acylcarnitines and ceramides were enriched in erythrocytes. Plasma and erythrocyte concentrations of plasmanyls and plasmalogens (endogenous antioxidants) were decreased in both patient groups with a significantly more pronounced effect in FO/-. We confirmed the protective effect of OO in PN mixtures containing ω-3 PUFAs.

The effect of ω-3 polyunsaturated fatty acids on the liver lipidome, proteome and bile acid profile: parenteral versus enteral administration.

Parenteral nutrition (PN) is often associated with the deterioration of liver functions (PNALD). Omega-3 polyunsaturated fatty acids (PUFA) were reported to alleviate PNALD but the underlying mechanisms have not been fully unraveled yet. Using omics´ approach, we determined serum and liver lipidome, liver proteome, and liver bile acid profile as well as markers of inflammation and oxidative stress in rats administered either ω-6 PUFA based lipid emulsion (Intralipid) or ω-6/ω-3 PUFA blend (Intralipid/Omegaven) via the enteral or parenteral route. In general, we found that enteral administration of both lipid emulsions has less impact on the liver than the parenteral route. Compared with parenterally administered Intralipid, PN administration of ω-3 PUFA was associated with 1. increased content of eicosapentaenoic (EPA)- and docosahexaenoic (DHA) acids-containing lipid species; 2. higher abundance of CYP4A isoenzymes capable of bioactive lipid synthesis and the increased content of their potential products (oxidized EPA and DHA); 3. downregulation of enzymes involved CYP450 drug metabolism what may represent an adaptive mechanism counteracting the potential negative effects (enhanced ROS production) of PUFA metabolism; 4. normalized anti-oxidative capacity and 5. physiological BAs spectrum. All these findings may contribute to the explanation of ω-3 PUFA protective effects in the context of PN.