Armand Malnoe

Effects of parenteral lipid emulsions with different fatty acid composition on immune cell functions in vitro

BACKGROUND Numerous studies suggest that immune function may be compromised by lipid emulsions rich in polyunsaturated fatty acids (PUFAs). In our study, we compared the effect of a new olive oil-based lipid emulsion (ClinOleic) containing a moderate level of PUFAs, with emulsions based on soybean oil (Intralipid or Ivelip), on immune functions of human cell in vitro. METHODS Peripheral white blood cells were collected from healthy volunteers. Lymphocyte proliferation was evaluated by [3H]-thymidine incorporation after stimulation with either phytohemagglutinin (PHA) or antibodies against T-cell specific antigens. Lymphocytes subsets and T-cell activation markers (CD25 and HLA-DR) were measured by flow cytometry. The release of cytokines (interleukin [IL]-2, IL-1beta, and tumor necrosis factor-alpha [TNF-alpha]) was measured by enzyme-linked immunosorbent assay (ELISA), after lymphocytes or monocytes/macrophages stimulation with PHA or lipopolysaccharide (LPS). RESULTS A significant dose-dependent inhibition of thymidine incorporation was observed with Intralipid and Ivelip (incorporation down to 39.9% of control, p < .001) whereas ClinOleic showed no inhibitory effect. Activation antigen expression on both CD4+ and CD8+ T-cells tended to decrease with Intralipid (CD25: -53.4% on CD4+ and -57.4% on CD8+; HLA-DR: -61.5% on CD4+ and -58.5% on CD8+) but not with ClinOleic (from -2.9% for CD25 on CD4+ to 16.7% for HLA-DR on CD4+). Intralipid decreased significantly IL-2 production (-39.0%, p < .05) whereas ClinOleic had little effect (-13.0%, NS). Intralipid and ClinOleic tended to inhibit to a similar extent the release of pro-inflammatory cytokines (TNF-alpha: -21.5% and -34.8%, IL-1beta: -45.1% and -40.3%; respectively). CONCLUSIONS Our results suggest that an olive oil-based lipid emulsion could modulate immune response selectively, maintaining protective immunity and reducing inflammatory response. Olive oil may offer an immunologically neutral alternative to soybean oil for use in parenteral lipid emulsions.

Effect of low intake of n−3 fatty acids during development on brain phospholipid fatty acid composition and exploratory behavior in rats

The effect of dietary restriction of n−3 fatty acids during development on brain phospholipid fatty acid composition and exploratory behavior has been studied in male Sprague Dawley rats. Female rats were fed semipurified diets containing either 5.5% safflower oil or 6% soybean oil for 6 wk prior to mating and throughout gestation and lactation. Control rats were maintained on laboratory chow. The male pups were weaned to the diets of the dams except for one group which was switched from safflower to soybean oil at weaning. Behavioral studies and brain phospholipid analyses were conducted at 16–18 wk of age. Rats fed safflower oil showed significantly lower levels of 22∶6n−3 in phospholipids of synaptic membranes and myelin than rats fed soybean oil or chow. The decrease in 22∶6n−3 was compensated for by an increase in 22∶5n−6, the total content of polyunsaturated fatty acids remaining approximately constant. The brain phospholipid fatty acid composition of rats switched from safflower to soybean oil at weaning was similar to that of rats fed soybean oil throughout the experiment. There was no difference in spontaneous locomotor activity among the different dietary groups. However, rats raised on safflower oil displayed a significantly lower exploratory activity (horizontal movements and rearings) in a novel environment than rats fed soybean oil or chow. In contrast to the brain phospholipid fatty acid composition, there was no recovery of exploratory behavior in rats raised on safflower oil and switched to soybean oil at weaning suggesting a specific requirement of n−3 fatty acids during development.

Effect of In Vivo Modulation of Membrane Docosahexaenoic Acid Levels on the Dopamine-Dependent Adenylate Cyclase Activity in the Rat Retina

Abstract: We have studied the effect of a dietary deprivation of n‐3 fatty acids on the activity of the dopamine (DA)‐de‐pendent adenylate cyclase in the rat retina. Experiments were conducted in 6‐month‐old rats raised on semipurified diets containing either safflower oil (n‐3 deficient diet) or soybean oil (control diet). The levels of docosahexaenoic acid [22:6 (n‐3)] in retinal phospholipids were significantly decreased in n‐3 deficient rats (35–42% of control levels). This was compensated by a rise in 22:5 (n‐6), the total content of poly‐unsaturated fatty acids (PUFA) remaining approximately constant. Adenylate cyclase activity was measured in retinal membrane preparations from dark‐adapted or light‐exposed rats. The enzyme activity was stimulated by DA and SKF 38393 in a light‐dependent fashion. The activation was lower in rats exposed to light than in dark‐adapted animals, suggesting a down‐regulation of the DI DA receptors by light. The activation by guanine nucleotides and forskolin was also decreased in light‐exposed rats. There was no significant effect of the dietary regimen on the various adenylate cyclase activities and their response to light. Furthermore, the guanine nucleotide‐ and DA‐dependent adenylate cyclase activities of retinal membranes were found to be relatively resistant to changes in membrane fluidity induced in vitro by benzyl alcohol. The results indicate that in the absence of changes in total PUFA content, a decreased ratio of n‐3 to n‐6 fatty acids in membrane phospholipids does not significantly affect the properties of adenylate cyclase in the rat retina.

Phospholipid fatty acid composition and vitamin E levels in the retina of obese (fa/fa) and lean (FA/FA) Zucker rats

We have compared the fatty acid composition of the major classes of phospholipids in the retina of lean (FA/FA) and genetically obese (fa/fa) male Zucker rats. In all phospholipid fractions, there was a higher ratio of n-3 to n-6 fatty acids in obese animals whereas the total content of polyunsaturated fatty acids (PUFA) was unaffected by the genotype. Lower percentages of arachidonic acid (20:4(n-6)) were present in the phosphatidylcholine, phosphatidylinositol and phosphatidylserine fractions in the retina of obese rats. This was associated with a higher level of docosahexaenoic acid (22:6(n-3)) in these fractions. In addition, increased levels of dihomo-gamma-linolenic acid (20:3(n-6)) were present in the retinal phosphatidylcholine and phosphatidylethanolamine of obese animals. These results indicate that modifications of phospholipid fatty acid composition which have previously been reported in peripheral tissues of obese Zucker rats also affect the retina. Furthermore, the retinal levels of vitamin E were higher in obese than in lean rats suggesting differences in the tissue antioxidant status between these two genotypes.