Interactions between fatty acids and arginine metabolism: implications for the design of immune-enhancing diets.
BACKGROUND
Trauma increases the enzyme arginase, thus depleting arginine necessary for producing nitric oxide. Arginine and omega-3 fatty acids are components in immune-enhancing diets. These diets decrease infections in surgical patients, perhaps by preventing arginine deficiency. This study examines whether omega-3 fatty acids alter the metabolic fate of arginine. Thus, we hypothesized there could be differential effects of varying prostaglandins on regulation of arginase.


METHODS
Prostaglandins PGE1, PGE2, and PGE3 were tested using RAW 264.7 cells cultured in the presence of these prostaglandins for 24 hours. IL-13 (10 ng/mL) was added 24 hours later to induce arginase I. NO production was induced by adding LPS (2 microg/mL) to the cultures after another 24 hours.


RESULTS
Arginase activity (nmol/min/mg) was induced by all prostaglandins but significantly more by PGE1 (466.05+/-30.25) and PGE2 (248.45+/-15.05) than PGE3 (139.87+/-19.88; p < .002) when co-cultured with IL-13. Western blots correlated the increase in arginase I expression. Nitrate levels (microM) were inversely proportional to activity with PGE3 having the highest production (3.89+/-0.19) and PGE2 and PGE1 with the lowest (2.75+/-0.49 and 1.54+/-0.19, respectively). Inhibition of arginase I using nor-hydroxyarginine increased and equalized nitrate levels.


CONCLUSIONS
Different prostaglandins significantly alter the metabolism of arginine. Prostaglandins from omega-6 fatty acids increases arginase I expression. By decreasing arginase I expression, prostaglandins from omega-3 fatty acids may increase available arginine. The specific combinations of dietary fatty acids and arginine should be considered when tailoring dietary regimens.
Bansal
Vishal
V
Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Syres
Kimberly M
KM
Makarenkova
Valeryia
V
Brannon
Ryan
R
Matta
Benjamin
B
Harbrecht
Brian G
BG
Ochoa
Juan B
JB
D001119:Arginase / Q000378:metabolism*; D001120:Arginine / Q000172:deficiency / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D011453:Prostaglandins / Q000008:administration & dosage* / Q000494:pharmacology
D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D011453:Prostaglandins; D009569:Nitric Oxide; D001120:Arginine; D001119:Arginase