leukotriene-b4 and Weight-Gain

To determine whether conjugated linoleic acid (CLA)-induced body fat loss is dependent upon metabolism of CLA by Delta6-desaturase, cyclooxygenase, or lipoxygenase.. Mice were fed diets with or without CLA and inhibitors to either Delta6-desaturase (SC-26196), cyclooxygenase (aspirin), or lipoxygenase (nordihydroguaiaretic acid (NDGA)) for 2 weeks. Body fat percent, lean mass, fat pad weights, liver weight, and fatty acid concentrations were determined. A Delta6-desaturase index was calculated, and adipose tissue prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) concentrations were determined to confirm enzyme inhibition.. Inhibition of Delta6-desaturase and cyclooxygenase were confirmed. CLA caused a loss of body fat (P < 0.001). The body fat loss was blocked (P = 0.08) by the Delta6-desaturase inhibitor at a dose that decreased (P < 0.05) the calculated index. Aspirin and NDGA had no effect on body fat and did not interact with CLA.. Inhibition of Delta6-desaturase prevented CLA from being able to cause a body fat loss. Therefore, a desaturated metabolite of CLA appears to be involved in the CLA antiobesity effect. This effect of CLA does not seem dependent upon cyclooxygenase. Because lipoxygenase activity was not blocked by NDGA, we cannot draw conclusions about its importance in mediating the antiobesity effect of CLA.

Topics: Adipose Tissue; Adiposity; Animals; Aspirin; Cyclooxygenase Inhibitors; Dietary Fats; Dinoprostone; Eating; Enzyme Inhibitors; Leukotriene B4; Linoleic Acids, Conjugated; Linoleoyl-CoA Desaturase; Lipoxygenase; Lipoxygenase Inhibitors; Liver; Male; Masoprocol; Mice; Piperazines; Prostaglandin-Endoperoxide Synthases; Time Factors; Weight Gain

gamma-linolenic acid (GLA) has been reported to improve several inflammatory disorders through regulation of eicosanoid production. However, since GLA is a precursor of arachidonic acid, it may bring about increasing tissue arachidonic acid levels with subsequent pro-inflammatory events. To explore this possibility, we examined the effect of high-dose GLA acid on the fatty acid profile of immune cells, leukotriene B4 production by peritoneal exudate cells and immunoglobulin productivity of mesenteric lymph node lymphocytes of Sprague-Dawley rats. Male rats were fed 10% fat diets containing graded levels, 0, 20, 40 and 60% of GLA for 3 weeks. The results showed the distinction in activity of metabolizing GLA between immune cells and liver. Thus, in immune cells such as mesenteric lymph node and spleen lymphocytes and peritoneal exudate cells, more dihomo-gamma-linolenic acid was found than in the liver. Leukotriene B4 production by peritoneal exudate cells was significantly suppressed when fed the highest level of GLA suggesting a lower risk of allergic reaction. Moreover, immunoglobulin productivity in mesenteric lymph node lymphocytes was promoted by dietary GLA. The present study indicates that a high dose of GLA may exert anti-inflammatory effects through suppression of leukotriene B4 release and strengthening of gut immune system, thus ameliorating allergic reaction.

Topics: Animals; Cells, Cultured; Dietary Supplements; Dose-Response Relationship, Drug; Fatty Acids; gamma-Linolenic Acid; Immunoglobulins; Leukotriene B4; Lymph Nodes; Lymphocytes; Male; Organ Size; Peritoneum; Phospholipids; Rats; Rats, Sprague-Dawley; Spleen; Weight Gain

The aim of this present study was to investigate the effect of amount and degree of oxidation of dietary oil on type 2 T-helper cell (TH)-related immune responses. Four groups of BALB/c mice were fed either 50 g soyabean oil/kg (50-S), 50 g oxidized oil/kg (50-O), 150 g soyabean oil/kg (150-S) or 150 g oxidized oil/kg (150-O). After 14 weeks consuming the experimental diets, the mice were immunized with ovalbumin (OVA) plus Al and antigen-specific immunoglobulin (Ig)E, IgG1 and IgG2a, inflammatory mediators such as prostaglandin (PG) E2 and leukotriene (LT)B4 were determined. Higher hepatic microsomal cytochrome P450 was noted in mice fed 150 g oxidized oil/kg compared with those of other groups. OVA-specific IgG1 and IgE were higher in mice fed 150 g oxidized oil/kg compared with those of the other groups. The data suggested the interleukin (IL)-4: interferon (IFN)-gamma ratio was higher in mice fed 50 g dietary oxidized oil/kg compared with that of the 50-S group. The IL-5:IFN-gamma ratios were higher in the 150-S and 150-O groups than in the 50-S and 50-O groups. PGE2 and LTB4 produced by macrophages stimulated by lipopolysaccharide were highest in mice in the 150 g oxidized oil/kg group. The data suggested that an increased intake of oxidized oil might exert an unfavourable effect on the TH2 response involved in allergic disease.

Topics: Animals; Asthma; Cell Division; Cytokines; Dinoprostone; Energy Intake; Female; Immunoglobulin E; Immunoglobulin G; Inflammation Mediators; Leukotriene B4; Mice; Mice, Inbred BALB C; Ovalbumin; Oxidation-Reduction; Soybean Oil; Spleen; T-Lymphocytes, Helper-Inducer; Weight Gain

The effects of conjugated linoleic acid (CLA) on the levels of chemical mediators in peritoneal exudate cells, spleen and lung, and the concentration of immunoglobulins in mesenteric lymph node and splenic lymphocytes and in serum were examined in rats. After feeding diets containing either 0 (control), 0.5 or 1.0% CLA for 3 wk, there was a trend toward a reduction in the release of leukotriene B4 (LTB4) from the exudate cells in response to the dietary CLA levels. However, CLA did not appear to affect the release of histamine. A similar dose-response pattern also was observed in splenic LTB4, lung LTC4 and serum prostaglandin E2 levels, and the differences in these indices between the control and 1.0% CLA groups were all statistically significant. The reduction by CLA of the proportions of n-6 polyunsaturated fatty acids in peritoneal exudate cells and splenic lymphocyte total lipids seems to be responsible at least in part for the reduced eicosanoid levels. Splenic levels of immunoglobulin A (IgA), IgG, and IgM increased while those of IgE decreased significantly in animals fed the 1.0% CLA diet. This was reflected in the serum levels of immunoglobulins. The levels of IgA, IgG, and IgM in mesenteric lymph node lymphocytes increased in a dose-dependent manner, while IgE was reduced in those fed the higher CLA intake. However, no differences were seen in the proportion of T-lymphocyte subsets of mesenteric lymph node. These results support the view that CLA mitigates the food-induced allergic reaction.

Topics: Animals; Dietary Fats, Unsaturated; Energy Intake; Exudates and Transudates; Histamine Release; Immunoglobulins; Leukotriene B4; Leukotriene C4; Leukotrienes; Linoleic Acids; Lymph Nodes; Lymphocytes; Male; Organ Size; Peritoneal Cavity; Rats; Rats, Sprague-Dawley; Spleen; Weight Gain