Synthesis of cholesterol and total lipid by male and female rats fed beef tallow or corn oil

Male and female weanling rats were fed diets containing 2 or 42% of calories as corn oil or 40% as beef tallow plus 2% as corn oil until they were 12 or 18 weeks of age. Incorporation of C¹⁴-acetate into lipids of serum and liver and concentration of lipids in serum, liver, and carcass at the end of these periods were determined. Net synthesis of noncholesterol lipid was repressed by changing the diet from 2% to 42% of calories from either dietary fat in both sexes and at both ages. Cholesterol net synthesis was enhanced 29-fold in males and 22-fold in females fed 42% corn oil compared to 2% corn oil to the age of 12 weeks. It was enhanced only 2.6-fold for males and 3.4-fold for females by 40% beef tallow plus 2% corn oil. At 18 weeks of age cholesterol synthesis in males fed 42% corn oil was 7.3 and in females 9.1 times the value for those fed 2% corn oil. At this age the values for rats fed 40% beef tallow plus 2% corn oil were 1.2 and 3.7 times those for 2% corn oil fed rats of the respective sexes.     

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. Presented in part at the AOCS Sterol Symposium, April 1970, and the Federation of American Societies for Experimental Biology, April 1971. Scientific Series Paper No. 1536, Colorado Agricultural Experiment Station.     

Stimulation of lipid absorption in young rats by cholesterol: Early time changes and effects on pentobarbital sleeping time

Four groups of young male and female rats were fed a chow diet (0), chow plus 10% corn oil (F), chow plus 1% cholesterol (C), or chow plus 1% cholesterol plus 10% corn oil (CF) for 1, 2, 4 and 8 days. After 2 dats, male F, C and CF rats exhibited a shorter anesthesia period (−20 to −30%) when given pentobarbital. By 4 days, male F and C rats had pentobarbital sleeping times (PB-ST) 20% less than 0 rats. These effects were additive and CF rats had 40% shorter PB-ST. Reduction of PB-ST by cholesterol and corn oil was similar but slightly less in female rats. Liver lipid content doubled in 4 days in CF rats, and liver cholesterol was 4 times that of 0 rats. These changes and the increases in metabolism of barbiturate suggested changes in liver microsomal enzyme activities. Serum glutamic oxaloacetic and glutamic pyruvic transaminase, two enzymes reflective of liver damage, did not increase after 8 days on C, F or CF diets. Our results suggest that consumption of an animal sterol and a high lipid diet by laboratory rats, normally consuming a diet low in fat (3–4%), increases the ability of the animal to detoxify a barbiturate. Storage of absorbed dietary cholesterol in the liver may represent a major mechanism for maintaining extra hepatic cholesterol homeostasis.     

Oxidized cholesterol modulates age-related change in lipid metabolism in rats

For three weeks, male Sprague-Dawley rats at either four weeks (young) or eight months (adult) of age were pairfed one of the purified diets free of or containing either 0.2% of oxidized cholesterol mixture (cholesterol oxidation products) or 0.2% of cholesterol. Although the food intake was similar, dietary oxidized cholesterol lowered body weight gain in young rats, but did not increase relative liver weight, in contrast to the enlargement seen with dietary cholesterol. Oxidized cholesterol, compared to cholesterol, tended to reduce the activity of hepatic 3-hydroxy-3-methylglutaryl CoA reductase and cholesterol 7α-hydroxylase, particularly the latter in aged rats, and prevented the rise in the concentration of liver cholesterol at both ages. It also tended to increase the activity of hepatic δ6 desaturase, particularly in young rats. Moreover, oxidized cholesterol in relation to cholesterol influenced liver and serum lipid concentrations in different ways, and increased lipid peroxidation at both ages. The ratio of splenic CD4⁺/CD8⁺ T-lymphocytes increased with age, but the influence of cholesterol and oxidized cholesterol was comparable. Thus, oxidized cholesterol may specifically disturb growth and age-related changes in the lipid metabolism in rats.     

Serum cholesterol,triglycerides and total lipid fatty acids of rats in response to okra(hibiscus escuientus) seed oil

Tender pods of okra are commonly consumed vegetables in India. Okra seed kernel, like soybean, is a rich source of protein and fat. Its fat, with its appreciable linoleic acid content (>42%), prompted us to look into its metabolic utility in comparison with commonly consumed groundnut oil. Serum lipid profiles, with respect to cholesterol, triglycerides and total lipid fatty acids were determined in rats receiving okra seed oil at a level of 10% in the casein based diet which was adequate with respect to vitamins, minerals, etc. The control group received a casein based diet in which groundnut oil was the source of fat. Serum lipid profiles in this group were similarly monitored. The feeding trial was carried out for a period of 90 days. Results showed that serum cholesterol content of rats receiving okra seed oil was significantly lower compared to those consuming groundnut oil. A decreasing trend in total lipids as well as triglycerides was also evident in animals fed okra seed oil. Serum fatty acid profiles showed a relatively higher proportion of long chain and polyunsaturated fatty acids in this group as compared to the group receiving groundnut oil. These results indicate that okra seed oil consumption has a potential hypocholesterolemic effect. To whom correspondence to be addressed. ¹Part of this work was presented at 45th Annual Meeting of Oil Technologists Association of India, New Delhi-Feb. 9–10, 1990.     

Effects of diets high in saturated fat and cholesterol on the lipid composition of canine platelets

The phospholipid composition of platelets from dogs on various experimental diets was determined. Thyroidectomized foxhounds were fed a control diet or the control diet supplemented with (1) beef tallow, (2) beef tallow and cholesterol, or (3) beef tallow, cholesterol, and safflower oil for 23 weeks prior to isolation of platelets. Platelets from animals fed the control diet contained 36.7% phosphatidylcholine (PC), 22.8% phosphatidylethanolamine (PE), 18.4% sphingomyelin (Sph), 11.8% phosphatidylserine (PS), 6.3% phosphatidylinositol (PI), and 2.2% lysophosphatidylcholine. The PE was 77.6% in the plasmalogen form. No highly significant changes in the phospholipid class composition resulted from the experimental diets. Cholesterol supplementation of the diets, however, caused consistent alterations in the fatty acid compositions of the platelet phospholipids including increases in the percentages of 18∶1ω9 (oleic acid), 18∶2ω6 (linoleic acid), and 20∶3ω6 (homo-gamma linolenic acid) and a decrease in the percentage of 20∶4ω6 (arachidonic acid). Addition of safflower oil to the tallow-cholesterol diet partially reversed these effects. These cholesterol-induced alterations in fatty acid composition could be due to exchange with plasma lipids, de novo synthesis, or altered platelet metabolism. The mechanism remains to be determined. Der. Nelson’s current affiliation is the Lipid Metabolism Branch, Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute.     

Effect of polyestradiol on lecithin:cholesterol acyltransferase in male and female rats

The effects of two doses of polyestradiol phosphate on lecithin:cholesterol acyltransferase activity and on liver and plasma cholesterol levels have been studied on female and male rats. Both treatments increased the hepatic content of esterified cholesterol, but the LCAT activity expressed as a percentage of cholesterol esterification was unaltered. The progress of esterification was not affected by the administration of the hormone. The LCAT activity in terms of the initial rate of esterification was decreased by the high dose of estradiol. This decrease was associated with a reduction of free plasma cholesterol level, as there is a significant positive correlation between these two parameters. The findings suggest that the increased esterified cholesterol in liver of estradiol-treated rats is not mediated by an alteration in the LCAT activity.     

Effect of tibric acid on hepatic cholesterol synthesis in rats

Male albino rats were administered various oral doses of tibric acid daily for 1 week. Serum cholesterol and triglyceride levels were reduced, but total liver content of cholesterol, phospholipids, and triglycerides was increased. Tibric acid treatment suppressed the incorporation of both [¹⁴C] acetate and [³H] mevalonate into cholesterol by liver homogenates.     

Regulation of hepatic cholesterol synthesis from mevalonate in suckling and weaned rats

The conversion of mevalonic acid into total nonsaponifiable lipids (NSF) and digitonin precipitable sterols (DPS) by 5000 g liver supernatant fractions was compared in suckling and weaned rats. The incorporation of mevalonate into both NSF and DPS was low in fractions from suckling rats and very high in fractions from weaned rats. The results indicate that the activities of one or more of the enzymes catalyzing the conversion of mevalonate into squalene and squalene into cholesterol change after weaning and may act as regulatory step(s) for cholesterol synthesis in the livers of suckling rats. It is suggested that the reduced synthesis of cholesterol in the liver of suckling rats is caused by the cholesterol in the maternal milk, and the rapid rise in cholesterol synthesis after weaning is due in part to the dietary change accompanying weaning, and in part to an increased need for cholesterol by developing liver.     

Oral contraceptive and platelet lipid biosynthesis in female rats: Dose-response relationship

Female rats were treated with different doses of an oral contraceptive (ethinyl estradiol + lynestrenol) and lipid biosynthesis was studied in blood platelets by acetate incorporation into different fractions separated by thin layer chromatography. A marked increase in lipid biosynthesis was observed, especially in the sterol fractions (cholesterol and lanosterol-dihydrolanosterol). It was dose-dependent, observed after a lag-phase, maximal in 3 days and normalized in 8 days. Thus, the oral contraceptive studied here appears to modify platelet lipid biosynthesis for the entire life of the platelets.     

Hypercholesterolemia in rats: Combined effect of high cholesterol diet and female sex steroids

The influence of estradiol and a contraceptive steroid combination on plasma cholesterol was studied in female rats on both normal and high-cholesterol diets which did not contain thiouracil. The high-cholesterol diet resulted in moderate hypercholesterolemia without weight loss, even with prolonged feeding. Hypercholesterolemia was markedly accentuated in the presence of either endogenous or exogenous sex hormones.     

Dietary fat alters the distribution of cholesterol between vesicles and micelles in hamster bile

The type of dietary fat strongly affects the incidence of gallstones in the hamster model of cholesterol cholelithiasis. The present study was designed to determine whether dietary fats could affect gallstone formation by altering the microstructure (vesicular/micellar ratio) of cholesterol in bile. Golden Syrian hamsters from Sasco (Omaha, NE) or Charles River (Wilmington, MA) were fed nutritionally adequate semipurified diets to which were added: (i) 4.0% butterfat without added cholesterol; (ii) 1.2% palmitic acid plus 0.3% cholesterol; or (iii) 4.0% safflower oil plus 0.3% cholesterol. Gallstone incidence and the percentage of cholesterol in vesicles and micelles were determined after two- or six-week feeding periods. Three out of ten Sasco hamsters fed the 1.2% palmitic acid diet for two weeks had cholesterol stones, while none of the eight Charles River animals had stones. In the Sasco hamsters, a significant proportion of the biliary cholesterol was found in void volume vesicles (28.8%) and small vesicles (17.1%); Charles River hamsters had negligible proportions (1.1%) of cholesterol in void volume vesicles and 15.4% in small vesicles. Cholesterol gallstones were most abundant in Sasco hamsters fed 1.2% palmitic acid for six weeks (nine out of ten animals); the mean cholesterol saturation index of the bile was 1.27. A significant proportion of the biliary cholesterol was eluted in the void volume vesicles (21.4%) and in small vesicles (15.0%). Five of the eight identically treated Charles River hamsters had cholesterol stones; the cholesterol saturation index averaged 1.36, and the biliary cholesterol was present in void volume vesicles (31.3%) and small vesicles (14.3%). Vesicles were not detected in the bile of hamsters fed cholesterol-free diets, and none of these animals developed cholesterol gallstones. Safflower oil diets inhibited stone formation even though the cholesterol saturation index was above unity. After six weeks, biliary cholesterol transported in void volume vesicles was highest for Sasco hamsters (13.3%) as compared to Charles River animals (6.9%), but total cholesterol transported in void volume vesicles plus small vesicles was similar in both groups (33.5% vs. 26.2%), respectively. These results suggest that in both strains of hamsters dietary fat influences gallstone formation by modulating the vesicular/micellar distribution of biliary cholesterol. Apparently, the presence of cholesterol/phospholipid vesicles in bile is associated with cholesterol gallstone formation.     

Comparison of total fat,fatty acids,cholesterol, and other sterols in mayonnaise and imitation mayonnaise

Nine brands of mayonnaise and five brands of imitation mayonnaise were purchased from supermarkets in the Washington, DC, area. The samples were analyzed for total fat, fatty acids, sterols, and moisture. Little variation in total fat and saturated fatty acid values was observed among the brands of mayonnaise. The polyunsaturated fatty acid content of mayonnaise ranged from 28.0 to 47.9 g/100 g product. The cholesterol levels were divided between two ranges, 50-55 and 75-79 mg/100 g product. In contrast, there was wide variation in the lipid composition of the different brands of imitation mayonnaise. The total fat values for these products varied from 14.3 to 50.4 g/100 g product. The cholesterol content varied between 0 and 72 mg/100 g product; the latter figure equals the cholesterol content of many of the mayonnaise samples.     

The effect of a histidine-excess diet on cholesterol synthesis and degradation in rats

Feeding a diet high in excess histidine (5% L-histidine) resulted in hypercholesterolemia and enlargement of the liver in rats. To clarify the mechanism of the hypercho-lesterolemia cholesterol synthesis and degradation were followed. We found that hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in histidine-excess diet rats was significantly higher than in rats fed a basal diet. Incorporation of [³H]water into cholesterol of liver slices from rats fed the histidine-excess diet was higher than incorporation into liver slices from rats fed the basal diet (expressed per liver per 100 g body weight).In vivo incorporation of [³H]water into hepatic cholesterol was also higher, but the incorporation into cholesterol of the small intestine was lower in histidine-fed rats than in rats fed the basal diet (expressed per liver per 100 g body weight). Hepatic cholesterol 7α-hydroxylase activity was similar in both groups. The data suggest that the hypercholester-olemia caused by histidine-excess diet appears to be due to the stimulation of cholesterol synthesis in the liver.     

Response of plasma lipids to dietary cholesterol and wine polyphenols in rats fed polyunsaturated fat diets

This experiment was designed to evaluate the effects of dietary red wine phenolic compounds (WP) and cholesterol on lipid oxidation and transport in rats. For 5 wk, weanling rats were fed polyunsaturated fat diets (n−6/n−3=6.4) supplemented or not supplemented with either 3 g/kg diet of cholesterol, 5 g/kg diet of WP, or both. The concentrations of triacylglycerols (TAG, P<0.01) and cholesterol (P<0.0002) were reduced in fasting plasma of rats fed cholesterol despite the cholesterol enrichment of very low density lipoprotein + low density lipoprotein (VLDL+LDL). The response was due to the much lower plasma concentration of high density lipoprotein (HDL) (−35%, P<0.0001). In contrast, TAG and cholesteryl ester (CE) accumulated in liver (+120 and +450%, respectively, P<0.0001). However, the cholesterol content of liver microsomes was not affected. Dietary cholesterol altered the distribution of fatty acids mainly by reducing the ratio of arachidonic acid to linoleic acid (P<0.0001) in plasma VLDL+LDL (−35%) and HDL (−42%) and in liver TAG (−42%), CE (−78%), and phospholipids (−28%). Dietary WP had little or no effect on these variables. On the other hand, dietary cholesterol lowered the α-tocopherol concentration in VLDL+LDL (−40%, P<0.003) and in microsomes (−60%, P<0.0001). In contrast, dietary WP increased the concentration in microsomes (+21%, P<0.0001), but had no effect on the concentration in VLDL+LDL. Cholesterol feeding decreased (P<0.006) whereas WP feeding increased (P<0.0001) the resistance of VLDL+LDL to copper-induced oxidation. The production of conjugated dienes after 25 h of oxidation ranged between 650 (WP without cholesterol) and 2,560 (cholesterol without WP) μmol/g VLDL+LDL protein. These findings show that dietary WP were absorbed at sufficient levels to contribute to the protection of polyunsaturated fatty acids in plasma and membranes. They could also reduce the consumption of α-tocopherol and endogenous antioxidants. The responses suggest that, in humans, these substances may be beneficial by reducing the deleterious effects of a dietary overload of cholesterol.     

Effect of essential fatty acid deficiency on lipid metabolism in isolated fat cells of epididymal fat pads of rats

Lipogenesis, lipolysis, and stimulation of glucose conversion into lipid by insulin or prostaglandin E₁ were studied in isolated fat cells of the epididymal fat pads of rats fed a fat-free diet or this diet supplemented with 10% hydrogenated coconut oil or 10% safflower seed oil. Changes in fatty acid composition, characteristic of an essential fatty acid deficiency, were well advanced in the neutral lipid but had only started in the polar lipid of the fat cells of the epididymal fat pads of animals 3 months after weaning. Cellularity of the epididymal fat pads, as indicated by protein to lipid ratio of the fat cells, was influenced greatly by hydrogenated coconut oil in the diet irrespective of an essential fatty acid deficiency. Lipogenesis was increased in the fat cells of the animals fed the hydrogenated coconut oil diet 5 weeks after weaning but was not significantly different from that of the safflower fed animals 3 months after weaning. Incorporation of glucose into lipid, oxidation to CO₂, and basal lipolysis were not significantly different in the fat cells of the essential fatty acid deficient animals from those fed safflower oil 3 months after weaning, except in animals of the fat-free group based upon cell lipid. However, conversion of glucose to free fatty acid was significantly greater in the isolated fat cells of animals fed either the hydrogenated coconut oil or the fat-free diet than in those of animals fed the safflower oil supplement. The incorporation of glucose into lipid by isolated fat cells was stimulated significantly by insulin in young animals fed a fat-free diet, but the effect on lipogenesis appeared to be reversed in the fat cells of animals receiving safflower seed oil 3 months after weaning. Prostaglandin E₁ also appeared to stimulate the incorporation of glucose into lipid in the fat cells of the older animals receiving safflower seed oil. Differences in osmolarity produced large differences in utilization of glucose and release of lipid from isolated fat cells, but no significant differences were observed between the cells from animals fed the fat-free diet and those from the controls fed safflower oil. The results demonstrated the effects of diets containing fat or no fat on enzyme activities and membrane properties of fat cells of the epididymal fat pads of essential fatty acid deficient rats.     

Lung lipid synthesis from acetoacetate and glucose in developing rats in vitro

Acetoacetate (AcAc) and glucose were compared as energy sources and as precursors for lipid synthesis in the lungs of developing rats. Minced lung tissue was incubated with [3-14C]AcAc or [U-14C]glucose and the oxidation of each substrate to CO2 or its incorporation into tissue lipids was quantified. The highest rates of oxidation were obtained during the first 5 days for AcAc and the first 2 days of life for glucose and oxidation of AcAc was 3-4 times greater than that of glucose at all ages. Throughout postnatal development, the rates of nonsaponifiable lipid, fatty acid and hence total lipid (chloroform/methanol extractable) synthesis from AcAc were 2-3 times those of glucose. The highest rates of total lipid synthesis from AcAc and glucose were observed at birth. Glucose was utilized for glyceride-glycerol synthesis at a higher rate than AcAc. Similar patterns of incorporation of AcAc and glucose into various lipid classes were noted. Of the total lipids synthesized from AcAc and glucose, respectively, phospholipid plus monoglyceride accounted for 64% and 77%, triglyceride 13% and 13%, diglyceride plus cholesterol 11% and 4%, fatty acids 9% and 4%, and cholesteryl esters 3% and 1%. AT birth, the specific activities of all lipids except triglyceride derived from AcAc were greater than those from glucose. Rates of synthesis of all complex lipids declined with age. The results of these experiments demonstrate that AcAc is utilized more readily than glucose for energy production and lipid synthesis in developing rat lungs.     

压力利用率与锤耗的关系研究

主要从六面顶压机顶锤对合成块施压的过程中合成块所承受压力的受力分析,研究压力变化对锤耗的影响,总结出合成块组装高度设计、试验的理论依据,提出了检验组装高度的技术指标.     

Effect of dietary fat on the lipid composition and utilization of short-chain fatty acids by rat colonocytes

The objective of the present studies was to examine the effect of dietary fat on the lipid composition of rat colonocytes and their utilization of short-chain fatty acids (SCFA). Rats were fed 14% beef fat, fish oil or safflower oil plus 2% corn oil in a semi-synthetic base diet for 4 wk. Colonocytes were isolated and their lipid composition was examined. Feeding beef fat and fish oil resulted in an increase in monounsaturated fatty acids and a reduction in ω-6 fatty acids. Feeding fish oil resulted in an enrichment with ω-3 fatty acids. These was no dietary influence on the amount of either cholesterol or phospholipids of colonocytes. Fish oil feeding resulted in significant increase in colonocyte free fatty acids (FFA) as compared to other diets. Dietary fat was found to have no effect on SCFA utilization by colonocytes. Colonocytes were found to utilize SCFA in the order of butyrate ≥acetate ≥propionate. The presence of acetate and propionate in the medium had no effect on the rate of butyrate utilization.     

Effects of ethanol ingestion and dietary fat levels on mitochondrial lipids in male and female rats

The effects of sex, dietary fat levels, and ethanol ingestion on rat liver mitochondrial lipids have been studied. Two groups of male animals were fed either a low-fat diet for about 76 days or a high-fat diet for about 52 days, and two groups of female animals were fed the same low-fat diet for about 50 days or the high-fat diet for about 37 days. Ethanol was substituted isocalorically for carbohydrate and amounted to 36% of total calories. The total as well as individual concentrations of fatty acids, phospholipids, and neutral lipids were determined in all eight groups of animals. Variable changes were observed in the total fatty acid composition of mitochondria from each of the four groups of animals. After ethanol ingestion, there was a decrease in arachidonate/linoleate ratio in males, while no change was observed in females. Increasing the fat content of the diet decreased this ratio in both controls and experimentals, but it did not alter the effects of ethanol on either sex. Presumably, this was due to the fact that corn oil was the only source of lipid. After ethanol ingestion, the total fatty acid concentration increased in all groups of animals except the males fed the low-fat diet. A decrease was observed in this group. The same pattern of change was reflected in changes in total phospholipid concentrations. In each case, the majority of the concentration change in total phospholipid could be accounted for by changes in phosphatidylcholine (PC). Measurement of choline oxidase (C.O.) showed that ethanol ingestion increased C.O. activity only in the low-fat group of males. No change was observed in the other three groups. Chronic ethanol ingestion is known to increase the methylation of phosphatidylethanolamine (PE); therefore, in order to decrease PC, the increase in C.O. in the low-fat males must have been of sufficient magnitude to offset the increase in PE methylation. Increasing the fat content of the diet offset the effect of ethanol on C.O. in males. Neither ethanol nor fat exerted much effect on C.O. in females. These results emphasize the importance of dietary levels of fat as well as sex in the study of liver mitochondria structure and function in relation to ethanol metabolism. This work was presented at the AOCS Meeting, New York, May 1977, at which J.A.T. was an Honored Student Awardee.