Melvin M. Mathias

The relationship of dietary fats to prostaglandin biosynthesis

The direct and indirect evidence that the fatty acid composition of dietary fat is involved in the regulation of prostaglandin biosynthesis was reviewed. Direct evidence included effects of essential fatty acid deficiencies and excesses on endogenous tissue levels and production rates of prostaglandins by several tissues. Indirect evidence included lipolytic, platelet aggregatory, hypertensive, inflammatory and immune responses. In general, composition of dietary fat did not affect prostaglandin biosynthesis unless a biochemical essential fatty acid deficiency was induced or the linoleate to saturated fatty acids ratio of the dietary fat was greater than 5. Most results were interpreted in light of changing fatty acid composition; however, very few direct measurements have been made.

Quantitative relationships between dietary linoleate and prostaglandin (Eicosanoid) biosynthesis

Essential fatty acid deficiency consistently depresses eicosanoid (prostaglandin E2, F2, and I2 and thromboxane) biosynthesis independent of sampling protocols. Tissue fatty acid analyses support the hypothesis that the decrease is due in part to depression of arachidonate and accumulation of eicosatrienoate (n−9). Research on the alteration of eicosanoid biosynthesis by dietary linoleate supplementation is reviewed extensively. Responses of whole blood, lung, liver and heart eicosanoid synthesis to feeding eight concentrations of dietary linoleate between 0 and 27 energy percent are reported. It is concluded that stimulation, depression and no change in eicosanoid production could be equally well documented as a response to linoleate supplementation. Evidence for the obvious mechanism that alterations in precursor fatty acid composition are a possible explanation is fragmentary and inconsistent. The appropriate sampling techniques appear not to be established at this time and most likely are species, gender and tissue specific.

Vitamin E, Immunity and Disease Resistance

The effect of vitamin E on immune responses and disease resistance is now well established and has been covered in recent reviews (Axelrod, 1978; Nockels, 1978; Sheffy and Schultz, 1979; Tengerdy, 1978). Predictably, vitamin E ([dl])-α-tocopheryl-acetate) deficiency leads to impaired immune response and disease protection (Axelrod, 1978). Large doses of vitamin E, much larger than the presently accepted recommended minimal daily allowance, on the other hand, enhance certain immune responses and can lead to increased disease resistance in a number of animal species against a variety of infectious agents. Table I. illustrates this point.

The effect of dietary lipids on clotting times and rat serum and urine prostaglandin concentrations.

Abstract The main precursor of prostaglandins is arachidonate which is derived from elongation and desaturation of linoleic acid. The influence of increasing dietary levels of linoleate on clotting times and prostaglandin (PG) concentrations of rat serum and urine was evaluated. Five diets varying in linoleate calories between 0.4–28.8% were utilized. The urinary excretion of PGE 2 , PGE 1 , PGF 2α , 6-keto-PGF 1α and thromboxane B 2 doubled when the linoleate calories increased from 0.4 to 13.6% and remained at that level as the percent linoleate calories increased to 28.8. In a second experiment, 3 diets varying in linoleate calories between 0.2 and 11% were utilized. As linoleate calories increased from 7.0 to 11%, the urinary levels of PGE 2 , PGE 1 , thromboxane B 2 , and 6-keto-PGF 1α approximately doubled. No differences in clotting times or in serum PG or thromboxane B 2 values were observed. The lack of effect is discussed.

Dietary lipid, fatty acid synthesis and cholesterol metabolism in aging rats

Male and female rats were fed diets containing 2% of calories as corn oil or that plus 40% of calories as beef tallow or corn oil. After 3, 6, 12 and 18 months groups were given 4-14C-cholesterol ip, and feces were collected for 9 days. Just prior to necropsy3H-acetate was administered ip. Samples of serum, liver, heart and carcass were obtained for analysis. Concentrations of fatty acids and cholesterol, synthesis of those and recovery of ring-labeled steroid are reported. Mortality from acute respiratory disease was very high in male rats fed beef tallow or low fat diets and very low in those fed the corn oil diet. In females, only beef tallow diet resulted in a high mortality rate, and this was lower and at a later age than in males. The most notable effects of age were in relation to fatty acid synthesis and presence of14C-acidic steroid in the carcass. In 3-month-old rats both fats depressed fatty acid synthesis in comparison to the low fat diet. At later ages beef fat ceased to depress fatty acid synthesis in both sexes. Corn oil continued to depress fatty acid synthesis up to 12 months in males and 18 months in females. The presence of14C-acidic steroid in carcass was substantial in 6-month-old rats and constituted ca. 40% of recovered14C in 18-month-old rats. The possibility that the increase in acetate incorporation into fatty acids with age in fat feeding is related to chain elongation rather than de novo synthesis is discussed. Both the presence and amount of acidic steroid in the carcass are notable and may be of importance in constructing models of cholesterol turnover.

Copper deficiency depresses rat aortae superoxide dismutase activity and prostacyclin synthesis

Prostaglandin synthesis shows dependence on lipid hydroperoxides and resultant oxygen derived radical formation. In view of the importance of dietary copper in cytosolic copper dependent superoxide dismutase (Cu/Zn SOD) activity and the role of SOD in oxygen radical formation, the influence of dietary copper on prostacylin (PGI2) synthesis and SOD activity in rat aorta was examined. Copper deficient (0.5 micrograms Cu/g diet) rats showed a significant 47% reduction in PGI2 synthesis rates by aortic ring incubations in comparison to copper adequate (6.0 micrograms Cu/g diet) animals. Aortic SOD activity was reduced by 46% in copper deficiency in comparison to copper adequate animals. Marginal dietary copper (1.6 micrograms Cu/g diet) significantly reduced aortic SOD activity by 32% but was without effect on aortic ring incubation PGI2 synthesis. These results indicate that dietary copper deficiency, and the resultant decrease in SOD activity, depresses aortic PGI2 synthesis.

Acetylcholine induces vasodilation and prostacyclin synthesis in rat lungs.

Acetylcholine causes pulmonary vasodilation, but its mechanism of action is unclear. We hypothesized that acetylcholine-induced pulmonary vasodilation might be associated with prostacyclin formation. Therefore, we used isolated rat lungs perfused with a recirculating cell- and plasma-free physiological salt solution to study the effect of acetylcholine infusion on pulmonary perfusion pressure, vascular responsiveness and lung prostacyclin production. Acetylcholine (20 micrograms infused over 1 minute) caused immediate vasodilation during ongoing hypoxic vasoconstriction and prolonged depression of subsequent hypoxic and angiotensin II-induced vasoconstrictions. Both effects of acetylcholine were abolished by atropine pretreatment. The prolonged acetylcholine effect, but not the immediate response, was blocked by meclofenamate, an inhibitor of cyclooxygenase. The prolonged effect, but not the immediate response, of acetylcholine was associated with an increase in perfusate 6-keto-PGF1 alpha concentration. The acetylcholine stimulated increase in 6-keto-PGF1 alpha production was inhibited by meclofenamate and by atropine. Thus, blockade of prostacyclin production corresponded with blockade of the prolonged acetylcholine effect. In conclusion, acetylcholine caused in isolated rat lungs an immediate vasodilation and a prolonged, time-dependent depression of vascular responsiveness. Whereas both acetylcholine effects were under muscarinic receptor control, only the prolonged effect depended on the cyclooxygenase pathway and, presumably, prostacyclin synthesis.

THE EFFECT OF VITAMIN E ON PROSTAGLANDIN LEVELS IN THE IMMUNE ORGANS OF CHICKS DURING THE COURSE OF AN E COLI INFECTION

Abstract The effect of dietary vitamin E supplementation on prostaglandin levels in the bursa and spleen of E. coli infected chicks was studied in two separate but similar experiments. In the first experiment Single Comb White Leghorn chicks were fed either a control diet (adequate in vitamin E) or a supplemented diet (containing an additional 300 IU per kilogram) and sacrificed at 21 days at several time points after infection. Infection had its maximum effect on PGE 2 and PGF 2α at 1 to 4 h post infection in the spleen and 24 to 48 h in the bursa. Vitamin E reduced PGF 2α levels in bursa but not in the spleen. In the second experiment the use of broiler chicks provided enough tissue to also determine thromboxane B 2 and 6-keto PGF 1α levels. Broiler chick bursa levels of PGE 2 , PGF 2α , 6-keto PGF 1α and thromboxane B 2 were depressed by vitamin E supplementation whereas only PGF 2α was decreased in the spleen. Infection resulted in increased levels of PGE 2 , PGF 2α and thromboxane B 2 in the spleen but not in the bursa.

Dietary fat saturation and cholesterol and fatty acid synthesis in aging rats

Male and female rats were fed 40% of calories as beef tallow (BT) (polyunsaturated to saturated (P:S) fatty acid ratio = 0.17) or a mix of safflower oil and beef tallow to give a P:S of 0.94 (M) in a nutritionally complete diet. Groups were killed at 9, 12, 15, 18, and 21 months of age and fatty acid and cholesterol concentration and synthesis in liver in vivo were measured. Serum cholesterol concentration and appearance of newly synthesized lipid were also determined. Serum cholesterol concentration increased with age regardless of diet. Fatty acid synthesis from alanine was generally similar to that reported for acetate in response to variables, being higher in females than males and in males consuming BT diet than those consuming M diet. Cholesterol synthesis from alanine was similar to that reported from acetate with regard to sex effect (females higher than males), but did not differ in response to diet. The latter is contrary to reports for acetate incorporation, which has been higher for more polyunsaturated dietary fats. Female rats exhibited very high rates of incorporation of alanine into both fatty acids and cholesterol at 12–18 months of age when they were fed beef tallow. This effect was not observed in females fed mixed fat nor in males. The 21 month old BT females had alanine incorporation rates more like the rats at early ages. This decline at advanced age may be the result of death of those with high synthesis rates and survival of those with lower rates.

Prostaglandin production and lipolysis in isolated rat adipocytes as affected by dietary fat.

The influence of dietary fat on prostaglandin production and lipolysis was tested in basal and norepinephrine stimulated adipocytes isolated from the epididymal fat pads of fasted rats. Seven diets varying in fat calories and polyunsaturation were utilized. No basal differences were noted for prostaglandin E2 production or lipolysis. Norepinephrine stimulated prostaglandin E2 and F2alpha production was significantly (P less than 0.01) increased with greater polyunsaturation of fat, but not by increased fat calories. Norepinephrine stimulated lipolysis was depressed by an increase in fat calories but was unaffected by the degree of polyunsaturation of fat. This is in vitro evidence against the concept that prostaglandins play a feedback regulator role in fat cell lipolysis since no correlation could be made between the two parameters.