Oil-fed Group Research Articles

Effect of corn and coconut oil-containing diets with and without cholesterol on high density lipoprotein apoprotein A-I metabolism and hepatic apoprotein A-I mRNA levels in cebus monkeys.

The mechanism(s) by which diets containing corn or coconut oil (31% of energy as fat) totally free of cholesterol or with 0.1% added cholesterol by weight (0.3 mg/kcal) affect plasma high density lipoprotein cholesterol (HDL-C), apoprotein (apo) A-I levels, apo A-I kinetics, and hepatic apo A-I mRNA concentrations were investigated in 26 cebus monkeys. Coconut oil-fed monkeys had elevated levels of plasma total cholesterol (217%), very low density lipoprotein plus low density lipoprotein cholesterol (331%), HDL-C (159%), and apo A-I (117%) compared with corn oil-fed animals. Although the addition of cholesterol to the corn oil diet significantly increased these parameters, no such effects were seen when cholesterol was added to the coconut-oil diet. Both the type of fat and cholesterol in the diet significantly affected HDL apo A-I metabolism by decreasing apo A-I fractional catabolic rate and increasing apo A-I production rate in the coconut oil-fed groups. The decrease in apo A-I fractional catabolic rate in the coconut oil-fed animals was also associated with an increase in the HDL core lipid to surface ratio. Liver apo A-I mRNA abundance was elevated in the coconut oil-fed groups; however, dietary cholesterol had no affect on these levels. The lack of parallel effects of dietary fat and cholesterol on apo A-I production rate and liver apo A-I mRNA levels suggests that the increase in the apo A-I production rate observed in the coconut oil-fed groups resulted from the fat-induced rise in liver apo A-I mRNA abundance, whereas the cholesterol-induced rise in the apo A-I production rate resulted from a mechanism other than changes in liver apo A-I mRNA levels.

Dietary fish oil effects on biliary lipid secretion and cholesterol gallstone formation in the African green monkey

We studied two groups of adult male African green monkeys to assess the effects of dietary fish oil on biliary lipid secretion and cholesterol gallstone formation. One group was fed 0.8 mg cholesterol/kcal and 42% of calories as fat with half of the fat calories derived from lard; the other group was fed a similar diet except for the isocaloric substitution of menhaden oil for lard. After 21/2 to 3 yr, necropsies were performed and the presence of gallstones was determined. Gallbladder bile specimens were analyzed for cholesterol saturation index, as well as for bile acid species and biliary phospholipid fatty acid composition. Our results showed that 67% of animals fed the lard diet had cholesterol gallstones compared with only 22% of animals in the group fed the fish oil diet (p = 0.08). The cholesterol saturation index of gallbladder bile also tended to be higher in the lard-fed group (1.15 ± 0.11) compared with the fish oil-fed group (0.86 ± 0.09, p = 0.06). No differences between the two dietary groups were noted in the percentages of the various types of bile acids. However, a greater percentage of ω-3 fatty acids and a lesser percentage of 18:1, 18:2 and 20:4 fatty acids were found in the biliary phospholipids from the fish oil-fed group compared with the lard-fed group. Biliary lipid secretion rates were then measured during isolated recirculating liver perfusion performed with a constant sodium taurocholate infusion. A significantly greater biliary phospholipid secretion rate was noted in the fish oil-fed animals compared with the lard-fed animals, whereas bile acid and cholesterol secretion rates were similar between the diet groups. We conclude that the increased biliary phospholipid secretion observed in the fish oil-fed group produced a less lithogenic gallbladder bile, which in turn resulted in a less frequent occurrence of gallstones in that group. In addition the increased phospholipid secretion was probably favored by the enrichment of biliary phospholipids with relatively less hydrophobic ω-3 fatty acids. (Hepatology 1991;14:679-684.)

Differential Effects of Fish Oil, Safflower Oil and Palm Oil on Fatty Acid Oxidation and Glycerolipid Synthesis in Rat Liver

Studies were conducted to explore the mechanisms by which dietary fish oil decreases hepatic triglyceride secretion. Forty-five rats (15/group) were fed purified diets containing 10% fat as either fish oil, safflower oil or palm oil for 10 d. Plasma triglyceride concentration was lowest in the fish oil-fed group followed by the groups fed safflower oil and palm oil. The liver's capacity to oxidize fatty acids was assessed by assays of mitochondrial and peroxisomal beta-oxidation pathways in whole homogenates. Additionally, key enzymatic activities in the biosynthesis of triglyceride (diacylglycerol acyltransferase, phosphatidate hydrolysis) and phosphatidylcholine (CTP:phosphocholine cytidylyltransferase) were assayed. Compared with those fed palm oil the fish oil-fed animals showed 25% greater mitochondrial beta-oxidation but this difference was not statistically significant (P = 0.1). Fish oil feeding led to 45% greater (P less than 0.05) peroxisomal beta-oxidation. Diacylglycerol acyltransferase activity was unaffected by the type of dietary fat and slightly (13%) but significantly (P less than 0.02) lower cytidylyltransferase activity due to fish oil feeding was observed. More strikingly, both fish oil and safflower oil diets significantly lowered phosphatidate hydrolysis by 37 and 22%, respectively, compared with the palm oil diet. This activity directly correlated (r = 0.68; P less than 0.001) with plasma triglyceride concentration. Thus, dietary fish oil might suppress triglyceride secretion by decreasing glycerolipid synthesis, an effect mediated by changes in one or more enzymes involved in phosphatidate catabolism.

Dietary fish oil effects on biliary lipid secretion and cholesterol gallstone formation in the African green monkey*1

We studied two groups of adult male African green monkeys to assess the effects of dietary fish oil on biliary lipid secretion and cholesterol gallstone formation. One group was fed 0.8 mg cholesterol/kcal and 42% of calories as fat with half of the fat calories derived from lard; the other group was fed a similar diet except for the isocaloric substitution of menhaden oil for lard. After 2 1/2 to 3 yr, necropsies were performed and the presence of gallstones was determined. Gallbladder bile specimens were analyzed for cholesterol saturation index, as well as for bile acid species and biliary phospholipid fatty acid composition. Our results showed that 67% of animals fed the lard diet had cholesterol gallstones compared with only 22% of animals in the group fed the fish oil diet (p = 0.08). The cholesterol saturation index of gallbladder bile also tended to be higher in the lard-fed group (1.15 +/- 0.11) compared with the fish oil-fed group (0.86 +/- 0.09, p = 0.06). No differences between the two dietary groups were noted in the percentages of the various types of bile acids. However, a greater percentage of omega-3 fatty acids and a lesser percentage of 18:1, 18:2 and 20:4 fatty acids were found in the biliary phospholipids from the fish oil-fed group compared with the lard-fed group. Biliary lipid secretion rates were then measured during isolated recirculating liver perfusion performed with a constant sodium taurocholate infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dietary fat on hepatic microsomal metabolism of 1,2-dimethylhydrazine

The present study was designed to examine the effects of different high fat diets on the liver microsomal metabolism of aminopyrine (AMP) and 1,2-dimethylhydrazine (DMH). Male Sprague-Dawley rats were fed either a low fat (5% corn oil) or high fat (20%) diets containing either corn oil, menhaden oil or beef tallow for a period of up to 9 months. Liver microsomes were assayed for N-demethylase activity for both AMP and DMH substrates at 2 weeks, 1, 6 and 9 months of diet only, and also after 1, 2, 5 and 10 DMH treatments (20 mg/kg body weight). The menhaden oil-fed group had consistently higher AMP demethylase activity, which increased up to 6 months and then declined. Beef tallow-fed rats had the highest DMH demethylase activity following DMH, but this decreased by 10 treatments. These data indicate that type and amount of dietary fat affects microsomal metabolism of carcinogens, which may enhance tumor initiation.

Dietary eicosapentaenoic acid and docosahexaenoic acid from fish oil. Their incorporation into advanced human atherosclerotic plaques.

The incorporation of fatty acids from dietary fish oil was measured in obstructive atherosclerotic plaques removed from 11 patients fed fish oil, rich in omega-3 fatty acids, for 6-120 days before a planned arterial endarterectomy. The fatty acids of plasma and atheroma were analyzed with special reference to docosahexaenoic acid (DHA, 22:6) and eicosapentaenoic acid (EPA, 20:5), the principal omega-3 fatty acids of fish oil. The omega-3 fatty acid content increased greatly in plasma from 0.9% of fatty acids to 14.8% in cholesteryl esters, from 3.8% to 22.1% in phospholipids, and from 1.3% to 21.9% in triglycerides. The omega-3 fatty acid content of the atherosclerotic plaques was also greater when compared with that of plaques removed from 18 non-fish oil-fed controls. The omega-3 fatty acid in cholesteryl esters of the plaques was 4.9% in the experimental group versus 1.4% in control plaque, in phospholipids it was 8.8% versus 1.8%, and in triglycerides it was 4.7% versus 0.7% (p less than 0.001 for each lipid class). The two major omega-3 fatty acids (DHA and EPA) behaved differently. Compared with their respective plasma levels, relatively more DHA than EPA was deposited into the plaques. Whereas the increase of omega-3 fatty acids in plasma reached a plateau 3 weeks after initiation of fish oil feeding, a linear increase in plaque omega-3 fatty acids continued with time. As a result of the changes in fatty acid composition, the lipid classes of both plasma and plaque had a higher unsaturation index in the fish oil-fed group.(ABSTRACT TRUNCATED AT 250 WORDS)

Moderate fish oil intake improves lipemic response to a standard fat meal. A study in 25 healthy men.

To test the hypothesis that conditioning with a practical dose of fish oil will reduce postprandial lipemia, 25 healthy men were matched according to levels of fasting plasma triacylglyceride and allocated to 6 weeks of either fish oil or olive oil supplements (5 g/day). After a 12-hour overnight fast at the termination of the study period, the subjects were given a standard test meal containing 89% of energy as fat (0.73 g fat/kg body wt, polyunsaturated to saturated fat ratio = 0.4). Vitamin A (429 retinol equivalents/kg body wt) was included to endogenously label the chylomicrons. Venous blood samples were obtained before the test meal and hourly thereafter for 8 hours. Chylomicrons were separated by ultracentrifugation, plasma triacylglyceride concentration was determined enzymatically, and retinyl ester levels were measured by liquid chromatography. Postprandially, the fish oil-fed group exhibited mean total and chylomicron triacylglyceride concentrations that were significantly (p less than 0.05) less than those of the olive oil-fed group. Both the fish oil- and olive oil-fed groups had similar rises in chylomicron retinyl esters during the first 2 hours, but after this time the postprandial response of the fish oil-fed group was consistently and significantly (p less than 0.05) less than the response of the olive oil-fed group. Our results suggest that improvement in lipemic response, whether due to enhanced chylomicron clearance or decreased chylomicron entry into the plasma pool, can be achieved at a much lower intake of fish oil than previously reported.

Effects of dietary supplementation with eicosapentaenoic acid or gamma-linolenic acid on neutrophil phospholipid fatty acid composition and activation responses

Previous data that alimentation with fish oil rich in eicosapentaenoic acid (EPA; 20:n-3) or vegetable oil rich in gamma-linolenic acid (GLA; 18:3n-6) can reduce symptoms of inflammatory skin disorders lead us to determine the effects of dietary supplements of oils rich in EPA or GLA on guinea pig (GP) neutrophil (PMN) membrane potential (delta gamma), secretion, and superoxide (O2-) responses. Weanling GPs were initially fed diets supplemented with olive oil (less than 0.1% EPA; less than 0.1% GLA) for 2 weeks, followed by a crossover by two sets of animals to diets supplemented with fish oil (19% EPA) or borage oil (25% GLA). At 4-week intervals, 12% sterile casein-elicited peritoneal neutrophils (PMN) were assessed for membrane polyunsaturated fatty acid (PUFA) profiles and FMLP-, LTB4-, and PMA-stimulated delta gamma changes, changes in flow cytometrically measured forward scatter (FWD-SC) (shape change), 90 degrees scatter (90 degrees -SC) in cytochalasin B-pretreated-PMN (secretion response), and superoxide responses, GP incorporated EPA and GLA (as the elongation product, dihomo-GLA or DGLA) into their PMN phospholipids by 4 weeks. The peritoneal PMN of all groups demonstrated broad resting FWD-SC and poor activation-related FWD-SC increases, suggesting in vivo activation. While secretion was comparable in the three groups in response to FMLP, there was a trend toward inhibition of LTB4-stimulated 90 degrees -SC loss in both fish and borage oil groups. This was significant only with borage oil (21.7 +/- 2.1 vs 15.3 +/- 1.2% loss of baseline 90 degrees -SC, olive vs borage: P = 0.03). PMN from borage- and fish oil-fed GPs showed a progressively lower O2- response to FMLP than the olive oil group (73.9 +/- 3.9 and 42.9 +/- 6.8% of olive oil response for borage and fish oils, respectively; P less than 0.005 and P less than 0.01, respectively, at 12 weeks), while PMA-stimulated O2- was inhibited only in the fish oil-fed group and only at 12 weeks (62.0 +/- 2.7% of control; P less than 0.025). We conclude that dietary supplementation with oils rich in PUFAs can modify PMN activation responses.

Modification of Rat Platelet Fatty Acid Composition by Dietary Lipids of Animal and Vegetable Origin

There were no statistically significant differences in final body weight or in food intake among groups of rats fed for 7 wk various fats of animal origin (lard fat and cod liver oil) or vegetable origin (corn, soybean and canola oils); the fats were fed as 10% of the diet (by wt) and were of varied fatty acid composition. Nevertheless, the mean weights of the kidneys from cod liver oil-fed animals were significantly higher than those of all other dietary groups. Platelets of rats from the groups receiving the animal fat contained significantly lower levels of linoleic acid, 18:2(n-6) [a precursor of arachidonic acid, 20:4(n-6)], than did platelets from rats receiving the fat of vegetable origin. Although the soybean-, canola- and cod liver oil-fed animals received substantial quantities of (n-3) fatty acids [alpha-linolenic acid, 18:3(n-3); eicosapentaenoic acid, 20:5(n-3); and docosahexaenoic acid, 22:6(n-3)], only the platelets of the latter two groups contained detectable levels of these fatty acids along with their products of elongation/desaturation/retroconversion. Platelets of the cod liver oil-fed group contained significantly less arachidonic acid, a major precursor of eicosanoids, than did those from all other dietary groups. However, platelet arachidonic levels also varied markedly among the other dietary groups. Diet-induced fatty acid changes observed in platelets of various dietary groups may influence platelet responses, including secretion, aggregation and biosynthesis of eicosanoids.

Effect of fish oil diet on hepatic lipid metabolism in nonhuman primates: lowering of secretion of hepatic triglyceride but not apoB.

African green monkeys were fed diets containing either 11% (by weight) fish oil or lard for 2.5 yr. To test the hypothesis that fish oil decreases hepatic secretion of triglyceride (TG) and apoB, livers from these animals were perfused with a fatty acid mixture [85% (w/w) oleate containing [14C]oleate and 15% n-3 containing [3H]eicosapentaenoic acid (EPA)] at a rate of 0.1 mumol fatty acid/min per g liver. Liver perfusate was sampled every 30 min during 4 h of recirculating perfusion. The concentration of triglyceride was similar for livers of animals of both groups and there was no difference between groups in the extent of incorporation of [3H]EPA or [14C]oleate into hepatic TG. While the secretion rate for the mass of TG was less in the fish oil-fed group (8.3 +/- 2.5 vs 18.3 +/- 4.4 mg/h per 100 g liver, P less than 0.05), the apoB secretion rate was similar (0.92 +/- 0.15 vs 1.01 +/- 0.13 mg/h per 100 g liver). Significantly less [3H]EPA was incorporated into secreted TG in the fish oil group (0.4 +/- 0.1 vs 1.0 +/- 0.1% infused dose/h; P less than 0.01). The rate of secretion of [14C]TG was similar for both groups (1.3 +/- 0.3 vs 1.4 +/- 0.1% infused dose/h for fish oil and lard groups, respectively). No significant diet-related differences in [3H]TG or [14C]TG fatty acid specific activity were observed for perfusate TG or hepatic TG. After perfusion, livers from fish oil-fed monkeys contained significantly more [3H]EPA in hepatic phospholipid than livers from lard-fed monkeys (19.5 +/- 1.8 vs 11.4 +/- 1.7% infused dose; P less than 0.01) although hepatic phospholipid mass concentrations were similar. The liver phospholipids of the fish oil group were enriched in n-3 fatty acid mass and were relatively depleted of oleate and linoleate. We conclude that although apoB secretion was unaffected, dietary fish oil significantly decreased hepatic TG secretion through relatively poor utilization of EPA for the synthesis of TG destined for secretion in VLDL; at the same time, increased incorporation of [3H]EPA into hepatic phospholipid accompanied the decreased incorporation into secreted TG and these events may be coupled.(ABSTRACT TRUNCATED AT 400 WORDS)

Learning and memory impairment in rats fed a high saturated fat diet

At the age of 1 month, three separate groups of Long-Evans rats were placed on 20% (w/w) fat (40% of calories) diets high in either saturated fatty acids (lard-based) or polyunsaturated fatty acids (soybean oil-based) or standard laboratory chow (Purina, 4.5% (w/w) fat). After 3 months, all rats were administered three tests of learning and memory--Olton's radial arm maze, a variable-interval delayed alternation task, and the Hebb-Williams maze series. The lard-fed group was impaired on all tests. The soybean oil-fed group was slightly impaired on some measures, relative to the chow-fed group, but consistently performed better than the lard-fed group. The results indicate that a diet high in saturated fatty acids can impair a wide range of learning and memory functions and are in line with biochemical and physiological evidence showing widespread effects of such diets on brain function.

Comparative Effects of Feeding Different Fats on Fatty Acid Composition of Major Individual Phospholipids of Rat Hearts

Comparative effects of feeding dietary linoleic (corn oil), oleic (olive oil), alpha-linolenic (soybean oil) and polyunsaturated fatty acids (fish oil) on lipid content and fatty acid composition of major individual phospholipids of rat hearts were examined. Feeding different diets did not result in lipid accumulation in the heart. Total triglyceride, nonesterified fatty acid, cholesteryl ester and phospholipid levels of heart tissue were not affected by the type of dietary fatty acid. However, heart free cholesterol levels decreased in both animals fed the olive and the fish oil diets. The percentage of individual phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and cardiolipin (CL) did not modify by changes in the dietary fat composition. Heart tissue from animals fed on olive oil were enriched with 18:1 (n-9 + n-7) fatty acid in all phospholipid fractions. Animals fed corn oil contained higher proportions of 18:2 (n-6) for PC, PE and CL, and the ingestion of the soybean oil diet increased 18:2 (n-6) for PC and CL in the same proportion as the ingestion of the corn oil diet. The levels of 22:6 (n-3) were increased in the fish oil-fed group, accompanied by both a decrease in total (n-6) fatty acids and an increase in total (n-3) fatty acids in the three phospholipid fractions. The 20:5 (n-3) was only detected in these animals. These results show that olive oil is as effective as fish oil in reducing heart cholesterol content and support earlier works suggesting the role of fish oil in preventing cardiovascular disease.

Influence of omega-3 and omega-6 fatty acid sources on prostaglandin levels in mice.

Studies from this laboratory, employing a hairless mouse model, have indicated that a polyunsaturated fatty acid source rich in omega-3 (n-3) fatty acid (FA) inhibits ultraviolet (UV)-carcinogenic expression, when compared to that of diets containing predominantly n-6 fatty acids. Omega-3 FA is a poor substrate for cyclooxygenase, the rate-limiting step in prostaglandin (PG) synthesis--the latter, particularly PGE2, are known to influence tumor biology. Based upon this rationale, plasma and cutaneous PGE2 levels were determined from hairless mice fed diets containing either 4% or 12% corn or menhaden oil. After two weeks on the respective diets, plasma PGE2 levels of corn oil-fed animals were approximately 6-fold greater than those of the menhaden oil-fed groups. A similar response was found in the dermis. Although the relationship to carcinogenic expression is unknown, dietary n-3 FA content can have a pronounced effect upon PGE2 levels and possesses the potential for influencing other immunomodulators.

Changes in lipid composition of liver microsomes and fatty acyl-CoA desaturase activities induced by medium chain triglyceride feeding.

Changes in fatty acid composition, microsomal delta 9- and delta 6-desaturase activities and liver contents of cholesterol and phospholipids were studied in rats fed medium chain triglyceride-supplemented diets. Weanling rats were divided into four groups and fed for three weeks a basal diet with different 10%-fat supplements: corn oil, medium chain triglyceride-corn oil, olive oil and medium chain triglyceride-olive oil. The highest relative content of saturated fatty acids corresponded to corn oil-fed animals. Both monounsaturated fatty acid content and delta 9-desaturase activity were higher in the animals fed olive oil diets than in corn oil-fed rats. The long chain polyunsaturated fatty acids of the n-3 series were increased in the olive oil and medium chain triglyceride-olive oil-fed groups probably due to the lower linoleic/alpha-linolenic ratios found in these two diets. The cholesterol/phospholipid molar ratio was unaffected by diet and the unsaturation index was only slightly changed in the four groups. Thus, some mechanism may be operative under these conditions to maintain the homeostasis of the membrane.

Modulation of hepatic ferrochelatase activity by dietary manipulation of mitochondrial phospholipid fatty acyl groups.

Ferrochelatase is an enzyme bound to the inner mitochondrial membrane, which is important in heme biosynthesis. Activity of purified ferrochelatase is affected by the presence of certain fatty acids. In the present study, we examined whether the activity of ferrochelatase is altered by dietary manipulation of the composition of mitochondrial membrane phospholipid fatty acyl groups. Rats were fed diets containing triolein, safflower or menhaden oil as 5% (w/w) of the diet. After 3 weeks, the animals were killed and liver mitochondria were isolated. Phospholipid fatty acid composition and ferrochelatase activity were assayed in the isolated mitochondria. Marked differences were seen. The proportion of oleic acid was highest in the triolein oil-fed group, that of linoleic and arachidonic acid was highest in the safflower oil-fed group and the proportion of eicosapentaenoic acid was highest in the menhaden oil-fed group. Ferrochelatase activity was greatest in the triolein oil-fed group and lowest in the menhaden oil-fed group regardless of whether the mitochondria were intact, sonicated or sonicated and treated with Tween 20. Mixing of mitochondria from menhaden oil-fed rats with triolein oil resulted in a significant increase in ferrochelatase activity. Membrane fluidity and activities of the mitochondrial membrane enzymes succinic dehydrogenase and cytochrome oxidase did not differ among the groups. We conclude that dietary manipulation of mitochondrial membrane phospholipid fatty acyl group composition can directly modulate hepatic ferrochelatase activity. This has potential application in the treatment of protoporphyria, the genetic disorder in which ferrochelatase activity is deficient.

Effect of the dietary alpha-linolenate/linoleate balance on lipid compositions and learning ability of rats. II. Discrimination process, extinction process, and glycolipid compositions.

Donryu strain rats through two generations were fed semi-purified diets supplemented with safflower seed oil (rich in linoleic acid) or with perilla seed oil (rich in alpha-linolenic acid), or a conventional laboratory chow (normal control diet). Brightness-discrimination learning ability was determined to be the highest in the perilla oil-fed group, followed by the normal group, and then by the safflower group, extending our earlier observation in a different strain of rat that alpha-linolenic acid is a factor in maintaining high learning ability (Yamamoto, N., M. Saitoh, A. Moriuchi, M. Nomura, and H. Okuyama. 1987. J. Lipid Res. 28: 144-151). After the brightness-discrimination learning test was administered, extinction of learning was measured. The time required for extinction was significantly longer in the safflower group than in either the perilla group or the normal diet group. Thus, the dietary alpha-linolenate/linoleate balance affected both the learning and the extinction of learning. The glycolipids of the cerebrum, cerebellum, and olfactory lobe were analyzed. Although the fatty acid compositions of the sulfatide and gangliosides were significantly different in the three parts of the brain, relatively little difference was observed in the fatty acids of glycolipids between the safflower group and the perilla group, suggesting that gross changes in brain glycolipids are not responsible for the differences in learning abilities between these dietary groups.

Effect of fish oil versus lard diets on the chemical and physical properties of low density lipoproteins of nonhuman primates.

Twenty-four adult male African green grivet monkeys were fed diets containing 42% of calories as lard or menhaden oil and 0.76 mg of cholesterol/kcal for a period of 8 months. Plasma samples from fasting animals were then taken and low density lipoproteins (LDL) were isolated by ultracentrifugation and agarose column chromatography. The LDL were analyzed chemically, and physical properties of the particles were studied by differential scanning calorimetry. The fish oil group had significantly smaller LDL (2.91 vs. 3.43 g/mumol), which contained fewer molecules per particle of all lipid constituents, except triglyceride, compared to the lard-fed animals. The fish oil-fed group had 15% of the total cholesteryl esters as n-3 fatty acyl species and the number of n-3, but not n-6, cholesteryl esters per LDL particle was proportional to LDL size. The numbers of saturated and monounsaturated cholesteryl ester species per LDL particle were highly correlated with LDL size for both diet groups. The LDL of the fish oil group had broad reversible thermotropic transitions that were 12-13 degrees C lower than those of the lard group. These transitions were indicative of order-disorder transitions of the LDL core cholesteryl esters. The peak transition temperature of LDL of the lard group was proportional to the ratio of saturated and monounsaturated to polyunsaturated cholesteryl ester species (CEFA ratio). However, the much lower peak transition temperature of the LDL of the fish oil group was not related to the CEFA ratio nor to the triglyceride content of the particles, but rather, to the n-3 cholesteryl ester content of the particles. Studies of cholesteryl ester model systems demonstrated that relatively small amounts of n-3 cholesteryl esters (less than 15% of total cholesteryl ester) could result in a lowering of the peak transition temperature of cholesteryl linoleate similar to that seen for intact LDL. We conclude that n-3 cholesteryl esters in small quantities have a marked disordering effect on the core cholesteryl esters of LDL, resulting in a striking depression of LDL transition temperature. In addition, we conclude that n-3 cholesteryl esters are preferentially utilized relative to n-6 cholesteryl esters to increase the number of cholesteryl esters per LDL particle with LDL enlargement in fish oil-fed animals.

Inhibition of atherosclerosis by cod-liver oil in a hyperlipidemic swine model.

We studied the effect of cod-liver oil on the development and progression of coronary artery disease in swine subjected to coronary balloon abrasion and fed an atherogenic diet for eight months. Sections from serial 3-mm segments of the coronary arteries were analyzed morphometrically in 7 pigs given a cod-liver-oil supplement and 11 control animals not given the supplement. Significantly less disease was seen in the sections from the animals fed cod-liver oil. The mean lesion area per vessel, mean luminal encroachment per vessel, and mean maximal luminal encroachment per vessel were reduced in animals fed cod-liver oil, as compared with controls, (P = 0.05, P = 0.016, and P = 0.011, respectively). Both groups of animals had severe hyperlipidemia throughout the study. Differences in the extent of coronary atherosclerosis were not related to differences in plasma lipid levels. Platelet arachidonate was markedly reduced, platelet eicosapentaenoic acid was increased, and serum thromboxane was decreased in the oil-fed group as compared with the control group. We conclude that in our animal mode, dietary cod-liver oil retarded the development of coronary artery disease, possibly through changes in prostaglandin metabolism.

Effect of dietarily provided linoleic and α-linolenic acid on the function of rat peritoneal macrophages

The objective of this study was to determine whether the function of the macrophage can be influenced by a diet rich in α-linolenic acid, a fatty acid known to lead to a markedly reduced level of prostaglandin synthesis. Rats were fed purified diets containing all essential nutrients and differing only in the source of fat. A diet containing 10% corn oil provided a low ratio of α-linolenic to linoleic acid, while one containing 10% linseed oil provided a high ratio. Two macrophage activities reported to be influenced by prostaglandins, phagocytosis and arginase activity, were examined in peritoneal macrophages. Phagocytic ability, as determined by uptake of yeast and carbon particles, was examined in macrophages from rats fed the diets for 6 weeks after weaning and was found not to differ between the 2 groups. Arginase activity was examined in macrophages from rats fed the diets for 4 weeks after weaning, but which were born to females fed the diets from the time the latter were weanlings. Arginase activity was found to be significantly higher in the corn oil-fed group. This is consistent with reports that prostaglandins are involved in the induction of arginase in peritoneal macrophages.

Improved graft patency associated with altered platelet function induced by marine fatty acids in dogs

Female mongrel dogs fed a marine fish diet rich in long-chain polyenoic fatty acids had improved patency of small-diameter arterial prosthetic grafts as compared to controls. Also, in vivo platelet function as measured by bleeding times was significantly prolonged. Eicosapentaenoic acid, not found in the serum of control animals, was present in relatively high concentrations in both the serum and a platelet-rich fraction of the marine oil-fed group. Eicosapentaenoic acid, unlike arachidonic acid, does not induce platelet aggregation and this phenomonon may account for the altered platelet function demonstrated in our animals and hence the improved graft patency. These data lend further support to the role of platelets in determining the patency of vascular grafts.