Effect of trans fatty acids on serum lecithin: cholesterol acyltransferase in rats.

An investigation was undertaken to study the effect of trans isomers of octadecenoic (18:1) and octadecadienoic (18:2) acids on serum lecithin:cholesterol acyltransferase (LCAT). Male rats of the Wistar strain were fed diets containing 15% fat for 9 months. The fat diets were either hydrogenated fat mixtures containing trans fatty acids, corn oil or lard. At the end of 9 months, rats were killed and serum cholesterol levels and LCAT activity were measured. It was found that free and total serum cholesterol levels were decreased when animals were fed trans fatty acids when compared with animals fed corn oil or lard. Although in vitro studies indicated that the percentage of cholesterol esterified in serum was not affected by the presence of dietary trans fatty acids, LCAT activity generally decreased when trans fatty acids were fed to rats for 9 months. In this study a negative correlation was found between serum free cholesterol and LCAT activity. Depressed total LCAT activity (mumoles of cholesterol esterified per hour per liter of serum) may have been related to a reduced amount of substrate (free cholesterol).

Incorporation and disappearance of trans fatty acids in rat tissues.

An investigation was undertaken to study the rate of incorporation and disappearance of trans isomers of octadecenoic and octadecadienoic acids from different tissues of rats fed 15% fat diets containing trans fatty acids for 3 months. At the end of 3 months some of the animals were killed and the remaining animals were changed over to a diet containing only trace amounts of trans fatty acids. Thereafter, representative animals were killed at 2, 4, 8, and 12 weeks. The fatty acid composition of tissue lipids was measured by gas liquid chromatography. Trans octadecenoate was primarily incorporated into phospholipids and triglycerides of plasma, liver, kidney, heart, adipose tissue, and red blood cells. Trans isomers of octadecadienoate accumulated in triglycerides of plasma, liver, kidney, heart, and adipose tissue while only small amounts accumulated in tissue phospholipids and cholesteryl esters. After removal of trans fatty acids from the diet, the time of disappearance of trans isomers of octadecenoate and octadecadienoate from tissues varied. With the exception of adipose tissue, 8 weeks after the trans fatty acid diet was discontinued, only negligible amounts of trans fatty acids were present in rat tissues, demonstrating that tissues studied can metabolize trans fatty acids.

Effect of administration of alpha- and gamma-tocopherol on tissue distribution and red cell hemolysis in rats.

Four groups of rats fed a tocopherol-free diet from weaning were administered, orally, 1.5 mg/day of either alpha- or gamma-tocopherol for 12 weeks or 5 mg/day of these compounds for 6 weeks. The fifth group was continued on the tocopherol-free diet. At the end of the experimental period the concentration of the two tocopherols was measured in plasma, RBC, liver, kidney, heart, spleen, muscle, testes and lungs. At the lower dose levels alpha-tocopherol, but not gamma-tocopherol, protected the RBC from hemolysis. At the higher levels both compounds were effective in this respect. While liver and spleen appeared to be the preferred storage tissues for both alpha- and gamma-tocopherols, a considerable amount of these compounds were found in RBC, muscle, heart and lung. The content of alpha-tocopherol in the liver was significantly greater than that of gamma-tocopherol. Whether this difference is the reflection of preferential utilization of gamma-tocopherol remains to be determined. The other tissues showed a more or less equal accumulation of the two compounds. At the higher levels of supplementation with the tocopherols the accumulation of gamma-tocopherol in most tissues was significantly greater than that of alpha-tocopherol.

Effect of an oral contraceptive on alpha-tocopherol levels in rat tissues.

PIP: The distribution of alpha-tocopherol was studied in female rats receiving .052 mg/day Enovid E for 4 days, and maintained on Vitamin E deficient, adequate, or enriched (10%) diets. The administration of Enovid produced slight increases of alpha-tocopherol in the liver and ovaries of Vitamin-E-deficient animals, and decreases of alpha-tocopherol in the plasma, erythrocytes, adrenals, and kidneys of Vitamin-E-supplemented rats. The magnitude of response of different tissues varied with increasing levels of dietary tocopherol. The results support previous findings on the effects of oral contraceptives on plasma cholesterol levels and lipoprotein distribution.^ieng

An evaluation in rats of nutritional status and reproduction performance post oral contraceptive therapy.

Adult female rats were orally administered either 0.052, 0.26 mg of Enovoid E (OC) or the vehicle, propylene glycol. Thereafter they were mated six, thirteen or twenty-seven days after the discontinuation of the drug. Chemical analyses i.e. cholesterol levels in plasma, liver and adrenals; tocopherol levels in plasma and liver; fatty acid patterns of cholesteryl esters of plasma liver, and adrenals, and plasma lipoproteins distribution, were performed on the pre-breeding (post-OC) females, mothers (following weaning of the young) and young female progeny, 10 weeks after weaning. Weanlings derived from mothers previously exposed to OC weighed more than their counterparts from mothers who had not been given the drug. A slight decrease of the survival time of the young during lactation was also observed in groups treated with higher levels of OC. Liver weights were increased in mothers as a result of pregnancy and lactation. Observed elevations of plasma cholesterol levels and cholesteryl arachidonate in the livers of the progeny were probably due to prolonged exposure to the 15% corn oil diet. In addition, previously reported metabolic effects of OC, such as increases in liver cholesteryl oleate, decreases in plasma and adrenal cholesteryl arachidonate, decreases in the alpha/beta lipoprotein ratio and alpha-tocopherol levels in plasma were confirmed.

PIP: The effects of Enovid E on nutrition and reproductive function were studied after discontinuation of the drug in adult female rats. The ani mals received either .052 or .26 mg of Enovid, and were mated 6, 13, or 27 days after cessation of treatment. Post-Enovid females (prebreeding) , mothers, and female offspring (10 weeks after weaning) were examined for plasma, liver, and adrenal concentrations of cholesterol, plasma and liver tocopherol levels, plasma, liver and adrenal fatty acid patterns of cholesteryl esters, and the distribution of plasma lipoproteins. Weanlings of treated mothers weighed more than those whose mothers were not treated. The higher dose tended to slightly decrease survival time of the young during lactation. Pregnancy and lactation increased liver weights in mothers. Increases in plasma cholesterol levels and liver cholesteryl arachidonate concentrations were observed in the offspring. Increases in liver cholesteryl oleate, decreases in plasma and adrenal cholesteryl arachidonate, and decreases in the plasma alpha/beta lipoprotein ratio and plasma alpha-tocopherol levels were observed.

Effect of oral contraceptives on plasma lipoproteins, cholesterol and alpha-tocopherol levels in young women.

PIP: The effects of oral contraceptives (OC) on plasma lipoprotein, cholesterol, and alpha-tocopherol levels were studied in 400 women volunteers. OC use caused plasma cholesterol levels to increase by about 7% and tocopherol levels to decrease by about 20%. The changes in cholesterol and tocopherol levels were significantly greater in women receiving vitamin E supplements (p less than .03; p less than .04, respectively). Plasma alpha-lipoproteins increased by 16%, while beta-lipoprotein levels decreased by 20%, resulting in a 30% decrease in the alpha-beta ratio. OC use diminished the usually high correlation between tocopherol and beta-lipoproteins. Plasma triglyceride and total lipid levels were significantly increased among OC users (p less than .05). Since the most pronounced changes occurred in the early stages of OC treatment, an adaptation with time is suggested.^ieng

Oral contraceptive-alpha-tocopherol interrelationships.

PIP: After observing that some of the side effects of the administration of oral contraceptive drugs to rats resemble those resulting from vitamin E deficiency, a possibility of an increased requirement for vitamin E during oral contraceptive therapy was considered. 4 groups each of 22 female weanling rats were placed on a 15% stripped corn oil diet adequate in all required nutrients except alpha-tocopherol. Group T had .01%, d,1-alpha-tocopheryl acetate incorporated into the diet; Group B had .05% butylated hydroxytoluene (BHT); Group N and NT had no additives. After 10 weeks when daily dosing with Enovid E (.052 mg in .1 ml propylene glycol) was initiated, Group NT was changed over to the tocopherol containing diet. The dosing continued for 4 days for half of the animals and for 28 days for the other half (Groups E) at which time the animals were sacrificed. 8 animals in each group served as a control and received the propylene glycol carrier only (Groups C). During the short experimental period, most of the animals lost weight whereas the long period of dosing resulted in lower gains in the vitamin E deficient than in E sufficient rats. Results showed that the effects of an oral contraceptive were less pronounced in E deficient rats. Lowering of plasma tocopherol levels was observed in rats receiving the drug. The vitamin E deficiency and the stress induced by the administration of an oral contraceptive were definitely not synergistic. It follows then that oral contraceptives do not aggravate biochemical changes when tocopherol status is inadequate.^ieng

Further studies of the effects of an anovulatory drug on lipid metabolism in the rat.

The effect of various levels of the oral contraceptive drug, Enovid E, on serum and liver lipid levels of adult female rats has been investigated. Doses ranging from 0.052 to 1.04 mg/day have been employed in rats fed control or cholesterol-containing diets. It has been confirmed that after administration of even low, physiological doses of the drug, esterified cholesterol in serum and adrenals decreases rapidly while at the same time it accumulates in the liver; cholesteryl oleate is increased while the relative amount of cholesteryl arachidonate is reduced. Serum phospholipids also are decreased; the alpha/beta lipoprotein ratio is significantly reduced due to the decrease of alpha-lipoproteins. Most of these changes also occur in cholesterol-fed rats. The observed effects are not related to a decreased food intake.