Eicosenoic and docosenoic acid incorporation in serum lipoproteins in rats fed rapeseed oil

Rats were fed rapeseed oil rich in eicosenoic (20∶1) and docosenoic (22∶1) acids for 7 days, and the fatty acid composition of the lipid classes of serum and serum lipoproteins was determined. Concentrations of 20∶1 and 22∶1 acids in the lipid classes were variable, especially among lipoproteins, and were a direct function of the alimentary state of the animal. The results suggest differences in the incorporation of the above acids among the major lipoprotein types and various lipid classes within a given lipoprotein type. The quick partial disappearance of very low density lipoproteins (VLDL) and of low density lipoproteins (LDL) containing 20∶1 and 22∶1 acids upon starvation and the preferential incorporation of these acids in the triacylglycerols of high density lipoproteins (HDL) are discussed.     

Effect of androgens on serum lipids and lipoproteins

The effects of androgens on lipid transport and metabolism have been reviewed. These effects are probably independent of the androgenic and anabolic activities of the androgens, although the molecular mechanism of action is still not known. Presumably the lowering by androgens of the concentrations of serum lipids and lipoproteins could be the consequence possibly of a primary, inhibitory effect on the synthesis of apolipoprotein A. In addition the role of increased lipolytic activities in plasma and of effects on intermediatry metabolism has been considered. Special Fellowship Awardee (1F11 NSO2245-01) from the National Institute of Neurological Diseases and Stroke One of eight papers presented at the symposium “Recent Advances in Drugs Affecting Lipid Metabolism,” AOCS Meeting, Houston, May 1971.     

Changes in lipids in liver and serum of rats fed a histidine-excess diet or cholesterol-supplemented diets

The influence of dietary excess (5%) L-histidine on serum and liver lipids was examined in rats. Feeding a histidine-excess diet for 3, 6, 14 or 30 days caused growth retardation, hepatomegaly and decreased liver lipids throughout the period of the experiment. Hypercholesterolemia was observed after feeding a histidine-excess diet for 6 days; then serum cholesterol continuously increased for 30 days. Serum triglyceride on day 30 in rats fed the histidine-excess diet showed a significant decrease compared to rats fed the basal diet. Serum phospholipids of rats fed the histidine-excess diet for 7 or 14 days showed a significant increase compared to rats fed the basal diet. When rats were fed a basal, histidine-excess or cholesterol-supplemented diet (0.5% and 1.0% cholesterol) for 6 days, the distribution of serum high density (HDL), low density (LDL) and very low density lipoprotein cholesterol in rats fed the histidine-excess diet was similar to that of rats fed the basal diet, whereas LDL-cholesterol increased and HDL-cholesterol decreased in rats fed the cholesterol-supplemented diet.     

Studies on lipid biosynthesis and cholesterol content of liver and serum lipoproteins in rats fed various phthalate esters

The effect of various phthalate ester plasticizers on lipid metabolism in rats was studied in vivo and in vitro. Di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DBP) inhibited (30–70%) hepatic sterologenesis from¹⁴C-acetate and¹⁴C-mevalonate in liver minces from rats fed the phthalates at a level of 2.5 mmoles/100 g of chow diet for 21 days; inhibition of¹⁴C-acetate incorporation into phospholipids, triglycerides, and steryl esters was reduced (35–70%) by DEHP and DBP feeding. In addition, serum cholesterol was lowered ca. 14 mg/dl with dietary DEHP or DBP but not with dimethyl phthalate (DMP). Hepatic total cholesterol levels were reduced significantly (31%, P<0.001) by DMP but not by DBP or DEHP. In other studies with DEHP fed at the 0.5% level in chow diets (1.3 mmoles/100 g), the incorporation (esterification) of³H-oleate into di- and triglycerides was reduced ca. 40%. Furthermore, the addition of DEHP (2%, 5 mmoles/100 g) to a semisynthetic diet containing 10% fat (hydrogenated coconut oil) resulted in changes in serum lipoprotein composition. The percentage of serum cholesterol in LDL rose from 22% to 34% while that in HDL fell from 78% to 66%; these changes occurred without net changes in serum cholesterol levels. Possible mechanisms for the inhibitory effect of phthalates on hepatic lipid biosynthesis are discussed. These studies are in partial fulfillment of the requirements for a Doctorate degree in Medical Sciences, McMaster University, Hamilton, Ontario, Canada.     

Serum lipids in spontaneously hypertensive rats and sprague-dawley rats fed menhaden oil

Dietary n-3 fatty acids, abundant in fish oil, exert a variety of effects that attenuate cardiovascular disease. In this study, we assessed the effect of fish oil (menhaden oil) on the serum lipid profile in hypertensive and normotensive rats. Spontaneously hypertensive rats (SHR) or Sprague-Dawley rats (SD) were fed either standard powdered diet (L-485), or L-485+5% menhaden oil (MO) or L-485+5% corn oil (CO) from weaning through eight months of age. Systolic blood pressure (BP) was periodically determined on SHR. Serum lipid profiles were performed at eight months on sample taken from the exposed hearts of anesthetized, fasted rats. SHR, compared with SD (diets combined) had significantly lower triaclyglycerols (TG), higher cholesterol (CHOL), higher high density lipoprotein cholesterol (HDL CHOL), higher low density lipoprotein cholesterol (LDL CHOL), and a higher LDL:HDL ratio. Comparison among diets (strains combined) revealed that rats fed MO had the lowest values for TG, CHOL, LDL and LDL:HDL; HDL did no vary with diet. SHR were less responsive to diet-induced changes than were SD; no decrease in TG, LDL or LDL:HDL was observed in SHR, nor was degree of hypertension altered in SHR by the MO or CO diet. In summary, MO is more effective than CO in shifting the lipid profile of rats toward one that is less atherogenic. However, the SD rat is more susceptible to diet-induced lipid modification than is the SHR.     

Essential fatty acids in trout serum lipoproteins,vitellogenin and egg lipids

This paper describes evidence of (n−3) and particularly of 22∶6 (n−3) fatty acid enrichment in trout lipoproteins as well as in vitellogenin, egg lipovitellin and oil globule. Among the lipoproteins, HDL and LDL were the main forms of blood lipid transport, whereas phospholipids and cholesteryl esters are the preferential chemical carriers for (n−3) fatty acid transport. However, cholesteryl esters were less important as esterified fatty acid carriers than in man. Taken together with the data obtained in mammals, our results suggest that there may be a relationship between EFA activity and the distribution of the EFA among the lipoprotein lipid fractions in vertebrates, irrespective of the EFA series. Administration of an (n−3) fatty acid deficient diet for three months prior to trout spawning produced a significant increase in egg lipid content, primarily as a result of the increase of the oil globule composed almost exclusively of triacylglycerols. This diet decreased the 22∶6 (n−3), as well as the (n−3) fatty acid contents of lipoproteins, lipovitellin, vitellogenin and the oil globule. In contrast, the (n−3) fatty acid level was always higher in lipoproteins and lipovitellin than in the vitellogenin and the oil globule. Moreover, the relative levels of 22∶6 (n−3) and total (n−3) fatty acids were quite similar in lipoproteins and lipovitellin on the one hand, and in vitellogenin and the oil globule on the other. These findings suggest a direct relationship between the two forms of plasma lipid transport and the two egg compartments. During ovogenesis, dietary lipids seemed to be diverted from the adipose tissue and essentially deposited in the egg.     

Lipid profiles of plasma lipoproteins of fasted and fed normal and choline-deficient rats

Three major density classes of lipoproteins and a residual protein (d>1.21) were isolated by ultracentrifugation from plasma of fasted, fed normal, and choline-deficient rats. Lipid extracts were obtained from total plasma and the various density classes of lipoproteins, and each extract was examined in detail by thin layer and gas chromatographies. The results indicated essentially identical compositions of molecular species of phosphatidyl choline, which suggested their rapid equilibration among the different plasma lipoprotein classes. In contrast, the molecular species of the triacylglycerols and cholesteryl esters showed significant differences among the chylomicrons, very low and low, and high density lipoproteins, which excluded the possibility of their ready equilibration in vivo. Omission of choline from diet resulted in a sharp and statistically significant decrease in all lipid components of the very low and low density lipoproteins within 2 days. After 10 days of choline deficiency, the lipid levels of chylomicrons and very low and low density lipoproteins were ca. one-half the levels found in the choline supplemented animals, and there were discernible distortions in their lipid composition. Reintroduction of choline led to a prompt return to normal levels and lipid composition of both chylomicron and very low and low density lipoprotein fractions. The lack of equilibration of the triacylglycerols among the lipoprotein classes under normal conditions and in choline deficiency demonstrates an as yet unrecognized source of compartmentation of plasma lipids.     

Myocardial lipids and nucleotides of rats fed olive oil or rapeseed oil

After 1 week, the level of myocardial fatty acids was 4 times greater in young rats fed high erucic rapessed oil than in those fed olive oil. The proportion of erucic acid was 5.6% in the mitochondrial fraction, 15.1% in the microsomal fraction, and 34.8% in the floating fat fraction. This incorporation of erucic acid into triglycerides of the floating fat was evidence of esterification. The changes in the mitochondrial lipids did not alter the content of adenine nucleotides of the myocardium nor its apparent capacity to oxidize substrates.     

Bromine levels in tissue lipids of rats fed brominated fatty acids

Lipids - Rats have been fed diets containing either 0.8% brominated corn oil or 0.5% of the ethyl ester of 9,10-dibromostearate or 9,10,12,13-tetrabromostearate. The brominated compounds were...     

Liver lipid alterations in rats fed arginine deficient diets

Arginine deficiency is associated with a marked increase in liver lipids in the rat. Triglyceride accumulation accounts for most of the fatty infiltration. Cholesterol concentration per gram of liver increased approximately 280% above control rats receiving dietary arginine. The percentage of phospholipids was significantly decreased in the arginine-deficient rat liver compared to controls. The fatty acid composition revealed a significant reduction in the percentage of palmitic, palmitoleic, oleic, and linoleic acids. However, both stearic and arachidonic acids were increased approximately 250 and 160%, respectively, in arginine-deficient livers compared to controls. Arginine deficiency in the rat causes a marked alteration in lipid metabolism similar to that observed with orotic acid feeding. The similarities of arginine deficiency and orotic acid feeding are discussed.     

Fatty acid composition of liver lipids in rats fed brominated fatty acids

Feeding rats diets containing brominated corn oil or di- or tetrabromostearate as the monoglyceride produced changes in fatty acid composition of liver lipids. Those changes associated with the feeding of brominated corn oil or tetrabromosterates could be explained by the accumulation of triglyceride, and the changes associated with the feeding of dibromostearate could result from the proliferation of a membrane system. A unique response to the feeding of diets containing brominated corn oil is an increase in the level of γ-linolenic acid.     

Monoethylenic isomers in cardiac lipids of rats fed partially hydrogenated herring oil

Compositional studies have been carried out to compare the monoethylenic fatty acid isomers of a partially hydrogenated herring oil with those found in the cardiac lipid of young rats fed this oil for 1 or 16 weeks. In general, all geometrical and positional isomers with chain lengths C₁₆, C₁₈, C₂₀ and C₂₂ found in the hydrogenated oil were also observed in cardiac lipid. Evidence was also obtained for the occurrence of β-oxidation in the catabolism of thecis andtrans isomers of these long chain acids. Presented at the AOCS Meeting, Ottawa, September 1972.     

Cardiac lipids in rats and gerbils fed oils containing C22 fatty acids

Docosenoic acid from rapeseed oil or herring oil in the diet of the young rat promoted an accumulation of cardiac lipid. The triglyceride fraction accounted for most of the deposited fat and contained a high concentration of the docosenoic acid. Liquid rapeseed oil, partially hydrogenated rapeseed oil or partially hydrogenated herring oil increased the amount of cardiac fatty acids at 1 week and led to the development of degenerative lesions at 16 weeks. Whale or seal oils low in C₂₂ fatty acids produced little effect on the amount of lipids in the heart of rats or gerbils. The latter species receiving 20% rapeseed oil in the diet showed a peak in cardiac lipid deposition at 4 days with similar levels of total fatty acids to that of rats, but with a lower concentration of erucic acid. Oil fromLimnanthes douglasii and hydrogenated herring oil also increased the amount of cardiac fatty acids in gerbils. A high intake of docosenoic acid was common to the animals displaying the cardiac alterations. Presented at the AOCS Meeting, Atlantic City, October 1971.     

Identification of noveltrans isomers of 20∶5n−3 in liver lipids of rats fed a heated oil

Trans polyunsaturated n−3 fatty acids are formed as a result of the heat treatment of vegetable oils. It was demonstrated previously that the 18∶3 Δ9cis, 12cis, 15trans containing acis Δ9 ethylenic bond was converted to a geometrical isomer of 20∶5n−3, the 20∶5 Δ5cis, 8cis, 11cis, 14cis, 17trans. In the present study, we have identified two new isomers of eicosapentaenoic acid, the Δ11 monotrans and the Δ11, 17 ditrans isomers in liver of rats fed a heated oil. These are formed as a result of the conversion of two of the main isomers of linolenic acid which are present in refined and frying oils, the 18∶3 Δ9trans, 12cis, 15cis and the 18∶3 Δ9trans, 12cis, 15trans.     

α-Tocopherol and serum lipoproteins

Twenty-six patients with clinically confirmed mammary dysplasia and five age-matched controls were treated with α-tocopherol, 600 mg/day. Serum samples collected on the 21st day of the menstrual cycle were analyzed for cholesterol in lipoprotein fractions, isolated by a combination of precipitation and ultracentrifugation techniques. Eighty-five percent of patients showed objective and subjective remission from disease following therapy. In mammary dysplasia patients, the ratio of serum cholesterol/high density lipoprotein cholesterol was higher than those in age-matched controls, an abnormality which was corrected by α-tocopherol therapy. Furthermore, as a result of therapy, high density lipoproteins increased and ester cholesterol associated with low density lipoproteins decreased. The results suggest that α-tocopherol may serve as an effective agent in treating patients with benign breast disease, as well as correct the inherent abnormality in serum cholesterol distribution in mammary dysplasia patients. Biochemistry Research Division, Department of Research Medicine.     

Effects of dietaryTrans-fat on biliary and fecal steroid excretion and serum lipoproteins in rats

Rats were fed cholesterol-free or cholesterol-enriched diets containing olive oil or partially hydrogenated corn oil at the 10% level for ca. 30 days (c-18∶1, 77.0% in the former diet andc-18∶1, 24.7% andt-18∶1, 42.5% in the latter). The linoleic acid content of these fat diets was made equivalent (1.7 energy%). After feeding cholesterol-free diets,trans fat compared tocis fat showed(a) no untoward effects on growth parameters, (b) a reduction of serum cholesterol levels without influencing concentrations of serum apolipoproteins A-I, B and E, (c) no effects on the bile flow and the concentration of biliary cholesterol and bile acids, (d) an increasing trend of fecal excretion of neutral and acidic steroids, both in terms of mg/day and mg/g feces, and (e) rather equivocal change in the composition of fecal, but not biliary steroids. Similar response patterns were also observed when cholesterol-enriched diets were fed except for a decrease in serum apo B and an ineffectiveness to increase fecal acidic steroids. Together with the results obtained from experiments simultaneously performed with safflower oil and completely hydrogenated corn oil, it seems that the steroid metabolism can be specificallymodified by the geometry of dietary fats.     

Changes in serum lipids in rats treated with oral cooper

Disturbances in lipid metabolism during copper deficiency in rats are well recognized. Copper deficiency is associated with the spontaneous retention of hepatic iron. Previous studies have reported that hypercholesterolemia and hypertriglyceridemia are associated with elevated hepatic iron concentrations in copper deficient rats. There was a direct relationship between the magnitude of blood lipids and the concentration of hepatic iron. Based on these data, it has been hypothesized that iron was responsible for the development of lipemia of copper deficiency. In this study was determined the effect of increasing doses of Cu(10, 20 and 50 ppm) in the diet, on the serum total lipids, total cholesterol, triglycerides (triacylglicerols), phospholipids, non-esterified fatty acids (NEFA) and liver iron and zinc concentrations in normal rats. The results were compared with normal rats that received a balanced diet containing 0.6 and 6 ppm of Cu, respectively. The results show that Cu-supplement diminished the cholesterol and triglyceride serum levels, increased the level of phospholipids, NEFA and concomitantly decreased the hepatic concentrations of Fe and Zn. There was a statistically significant (p < 0.05) simple correlation between triglycerides and liver Fe (r = 0.917; R2 = 64.03%), cholesterol and liver Zn (r = 0.872; R2 = 76.07%), cholesterol and liver Fe (r = 0.995; R2 = 99.10%), liver Fe and liver Cu (r = -0.612), liver Fe and liver Zn (r = 0.837), liver Cu and liver Zn (r = -0.612), and serum triglycerides and liver Zn (r = 0.967). The mechanism(s) by which Fe and Zn determine these changes is not known; none of the enzymes that act in cholesterol and triglyceride metabolism and biosynthesis require Fe and/or Zn. The increase of NEFA is due to changes in the process of lipolysis and re-esterification of the fatty acids in blood. However, additional studies are needed for the precise mechanisms of this interrelationships to be clarified.     

Effects of hydrogen peroxide on lipoproteins and associated lipids

Lipoproteins isolated from human or chimpanzee serum were treated with H₂O₂ and allowed to stand varying lengths of time before quantitative analysis in the ultracentrifuge. Marked instability of ultracentrifugal boundaries (convection) occurred during the first 24 hr, but diminished thereafter. Simultaneously, the quantity of lipoprotein decreased. The instability of boundaries in H₂O₂-treated samples was presumed to reflect loss of lipid-protein affinity and breakdown of lipoproteins under the force of ultracentrifugation. Analysis of extracted lipids showed that H₂O₂ caused little loss of phospholipid, significant loss of triglyceride, and apparent loss of cholesteryl ester. The latter loss, however, was accompanied by appearance of esterified cholesterol in the free cholesterol eluent. Apparently H₂O₂ converted some cholesteryl esters to a more polar form which was eluted later from the column, with the free cholesterol fraction. Gas chromatographic analysis of the fractions eluted from the column showed that selective degradation of polyunsaturated fatty acids was most marked with cholesteryl esters, somewhat less with triglycerides, and negligible with phospholipids. It was postulated that the loss of lipid-protein affinity caused by H₂O₂ in vitro may reflect a similar process in vivo, i.e., that one process contributing to development of atherosclerosis can be oxidation of lipoprotein, with loss of lipid-protein affinity and accumulation of lipid products in (or on) cells of the vascular system. Presented at the AOCS Meeting, Washington, D. C., April, 1968.     

Composition and concentration of lipoproteins in the serum of normal rats and rats deficient in essential fatty acids

A comparison is made of the concentration and chemical composition of serum lipoproteins of normal rats and rats deficient in essential fatty acids. The concentration of very low density lipoproteins (VLDL) and of low density lipoproteins (LDL) in serum of deficient rats is about half that found in normal rats, but the concentration of high density lipoproteins (HDL) is higher than normal and they contain an increased amount of cholesterol esters. The proportion of cholesterol that is esterified is much greater than normal in the serum of deficient rats. The deficiency of essential fatty acids also appears to result in compensating changes occurring in the composition of serum lipoproteins. In both VLDL and LDL of deficient rats the proportion of protein is raised and that of phospholipid lowered compared to normal, while the proportions of trigly ceride and cholesterol esters are unchanged.     

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.