Abstract
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.
Highlights
Parenteral nutrition (PN) is often associated with the deterioration of liver functions (PNALD)
Neither of the nutrition regimes resulted in the liver injury as evidenced by normal levels of serum aspartate transaminase (AST) or alanine transaminase (ALT). ω-3 polyunsaturated fatty acids (PUFA) administration, both enteral and parenteral, was associated with the reduction of serum triglyceride (Tg) concentration compared with controls or with animals provided only ω-6 PUFA
The first step in their synthesis is the release of fatty acid (FA) from the sn-2 position of membrane phospholipid or DAG followed by enzymatic conversion mediated by one of three enzymatic systems - COX, LOX or CYP450 (CYP2C, CYP2J and CYP4A families)
Summary
Parenteral nutrition (PN) is often associated with the deterioration of liver functions (PNALD). The first well-tolerated lipid emulsion (Intralipid) introduced to parenteral nutrition mixtures was based on soybean oil rich in ω-6 polyunsaturated fatty acids (PUFA)[6]. Besides their undeniable benefits comprising the dense source of non-protein calories, prevention of essential fatty acid (FA) deficiency and minimization of respiratory and metabolic stress[7], ω-6 PUFA serves as precursors for the synthesis of pro-inflammatory cytokines and eicosanoids and Intralipid administration was associated with serious adverse effects including inflammation and oxidative stress[8]. We hypothesized that the composition of the lipid emulsion itself and the parenteral route of administration bypassing the physiological mechanisms of dietary fat transport and distribution would influence the composition of the liver lipidome and/or proteome and may constitute one of the first triggers towards final pathology
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
