Lipid composition of liver microsomes in rats fed a high monounsaturated fatty acid diet

The fatty acid and cholesterol contents of tissue membranes are the determinants of membrane stability and functionality. This study was designed to evaluate the influence of a high monounsaturated fatty acid diet on the fatty acid composition of rat liver microsomes and on their cholesterol and lipid phosphorus content. Weanling animals were fed for 5 weeks with high fat diets containing olive oil or corn oil. Saturated fatty acids were increased and oleic acid decreased in microsomal total phospholipids and in the three major phosphoglycerides, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI), of rats fed corn oil as compared to the olive oil group. The percentage of linoleic acid was higher in the corn oil group, but only for total phospholipids and PC. Linoleic and alpha-linolenic metabolites were significantly increased in total phospholipids of olive oil-fed animals with respect to those fed corn oil. These changes were responsible for the low unsaturation index found in microsomal phospholipids of the corn oil group. The diet did not affect the microsome cholesterol or the lipid phosphorus content. These results show that, in olive oil-fed rats, the cholesterol content and the degree of unsaturation of liver microsomes was similar to that observed in weanling animals; this probably suggests an adequate maintenance of functionality of membranes in olive oil-fed animals.     

Omega-3 fatty acids increase the arachidonic acid content of liver cholesterol ester and plasma triacylglycerol fractions in the rat.

Recent studies have demonstrated that dietary fish oils rich in eicosapentaenoic acid (C20:5,omega 3) lower the content of arachidonic acid and its metabolites in plasma and tissue phospholipids. The present study examined the fatty acid composition of cholesterol ester and triacylglycerol fractions from plasma and livers of rats fed diets enriched with saturated fatty acids (beef tallow), alpha-linolenic acid (linseed oil) or eicosapentaenoic acid (fish oil). Feeding diets containing linseed oil or fish oil for 28 days increased arachidonic acid (C20:4,omega 6) levels in the cholesterol ester fraction of liver and in the triacylglycerol fraction of the plasma lipids. Plasma cholesterol esters were depleted of C20:4,omega 6 after feeding of the diet containing either linseed oil or fish oil. The changes in C20:4,omega 6 content cannot be explained by alterations in cholesterol ester or triacylglycerol pools of plasma and liver. These results suggest that the decrease in phospholipid C20:4,omega 6 content generally observed after fish oil consumption may be partly due to a shift of C20:4,omega 6 from phospholipid to the triacylglycerol and/or cholesterol ester pools in the same tissue. Triacylglycerols and cholesterol esters may therefore play a buffering role in the homeostatic maintenance of tissue phospholipid levels of arachidonic acid.     

Suppression of hepatic fatty acid synthase by feeding alpha-linolenic acid rich perilla oil lowers plasma triacylglycerol level in rats

This study was performed to determine the effects of dietary perilla oil, a n-3 alpha-linolenic acid (ALA) source, on hepatic lipogenesis as a possible mechanism of lowering triacylglycerol (TG) levels. Male Sprague-Dawley rats were trained for a 3-hour feeding protocol and fed one of five semipurified diets as follows: 1% (w/w) corn oil control diet, or one of four diets supplemented with 10% each of beef tallow, corn oil, perilla oil, and fish oil. Two separate experiments were performed to compare the effects of feeding periods, 4 weeks and 4 days. Hepatic and plasma TG levels were decreased in rats fed perilla oil and fish oil diets, compared with corn oil and beef tallow diets. The activities of hepatic lipogenic enzymes such as fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase, and malic enzyme were suppressed in the fish oil, perilla oil, and corn oil-fed groups, and the effect was the most significant in the fish oil-fed group. Also, the activities of glycolytic enzymes, glucokinase, and L-pyruvate kinase showed the similar trend as that of lipogenic enzymes. The activity of FAS, the key regulatory enzyme in lipogenesis, was positively correlated with hepatic and plasma TG levels and reduced significantly in the perilla oil-fed group compared with corn oil-fed group. In addition, the FAS activity was negatively correlated with the hepatic microsomal content of EPA and DHA. In conclusion, suppression of FAS plays a significant role in the hypolipidemic effects observed in rats fed ALA rich perilla oil and these effects were associated with the increase of hepatic microsomal EPA and DHA contents.     

Dependence on dietary cholesterol for n-3 polyunsaturated fatty acid-induced changes in plasma cholesterol in the Syrian hamster.

Male Syrian hamsters consumed diets containing incremental increases in dietary n-3 fatty acids from fish oil with either low (0.015% w/w) or moderate (0.1% w/w) dietary cholesterol content. Animals consuming diets containing moderate cholesterol, but not animals consuming diets containing low cholesterol, had increased plasma very low (VLDL)- and low density lipoprotein (LDL)-cholesterol levels with increasing fish oil consumption. The plasma concentration of high density lipoprotein (HDL)-cholesterol decreased by 43 and 32% with the consumption of the highest fish oil diets in the low and moderate dietary cholesterol groups, respectively. Hepatic LDL-receptor binding activity did not change with the consumption of low cholesterol diets, but gradually decreased with fish oil consumption in animals consuming the moderate cholesterol diets. Hepatic LDL-receptor binding and plasma LDL-cholesterol levels of the different dietary fish oil groups were highly correlated (r = -0.91). Fish oil consumption also caused an increase in hepatic free cholesterol but a decreased cholesteryl ester content. Therefore, in the Syrian hamster, the consumption of n-3 fatty acids increases LDL-cholesterol levels which can be partially explained by decreased hepatic LDL-receptor binding and this response to dietary n-3 fatty acids is dependent on the dietary cholesterol content. However, the effects of dietary n-3 fatty acids on HDL-cholesterol are independent of dietary cholesterol content.     

Fish oil decreases hepatic cholesteryl ester secretion but not apoB secretion in African green monkeys

Two groups of African green monkeys were fed diets containing 40% of calories as fat with half of the fat calories as either fish oil or lard. The fish oil-fed animals had lower cholesterol concentrations in blood plasma (33%) and low density lipoproteins (LDL) (34%) than did animals fed lard. Size and cholesteryl ester (CE) content of LDL, strong predictors of coronary artery atherosclerosis in monkeys, were significantly less for the fish oil-fed animals although the apoB and LDL particle concentrations in plasma were similar for both diet groups. We hypothesized that decreased hepatic CE secretion led to the smaller size and reduced CE content of LDL in the fish oil-fed animals. Hepatic CE secretion was studied using recirculating perfusion of monkey livers that were infused during perfusion with fatty acids (85% 18:1 and 15% n-3) at a rate of 0.1 mumol/min per g liver. The rate of cholesterol secretion was less (P = 0.055) for the livers of fish oil versus lard-fed animals (3.3 +/- 0.5 vs. 6.0 +/- 1.2 mg/h per 100 g, mean +/- SEM) but the rate of apoB secretion was similar for both groups (0.92 +/- 0.15 vs. 1.01 +/- 0.13 mg/h per 100 g, respectively). The hepatic triglyceride secretion rate was also less (P less than 0.05) for the fish oil-fed animals (8.3 +/- 2.5 vs. 18.3 +/- 4.4 mg/h per 100 g). Liver CE content was lower (P less than 0.006) in fish oil-fed animals (4.1 +/- 0.8 vs. 7.4 +/- 0.7 mg/g) and this was reflected in a lower (P less than 0.04) esterified to total cholesterol ratio of perfusate VLDL (0.21 +/- 0.045 vs. 0.41 +/- 0.06). The hepatic VLDL of animals fed fish oil had 40-50% lower ratios of triglyceride to protein and total cholesterol to protein. From these data we conclude that livers from monkeys fed fish oil secreted similar numbers of VLDL particles as those of lard-fed animals although the hepatic VLDL of fish oil-fed animals were smaller in size and relatively enriched in surface material and depleted of core constituents. Positive correlations between plasma LDL size and both hepatic CE content (r = 0.87) and hepatic VLDL cholesterol secretion rate (r = 0.84) were also found.(ABSTRACT TRUNCATED AT 400 WORDS)     

Influence of dietary fat on the lipid composition of rat brain synaptosomal and microsomal membranes.

The modulation of rat brain microsomal and synaptosomal membrane lipid by diet fat was examined. Brain synaptosomal and microsomal membrane composition was compared for rats fed on diets containing either soya-bean oil (SBO), SBO plus choline, SBO lecithin, sunflower oil (SFO), chow or low-erucic acid rape-seed oil (LER) for 24 days. Cholesterol and phosphatidylcholine levels in both membranes were altered by diet. Diet fat also affected the microsomal content of sphingomyelin. Change in membrane phosphatidylcholine level was related to the relative balance of omega-6, omega-3 and monounsaturated fatty acids within the diets fed. The highest phosphatidylcholine levels appeared in membranes of animals fed on SBO lecithin and the lowest in those fed on LER. Microsomal membrane cholesterol and sphingomyelin content increased by feeding on SBO lecithin. In both synaptosomal and microsomal membranes a highly significant correlation was observed between membrane phosphatidylcholine and cholesterol content. The fatty acyl composition of phospholipids from both membranes also altered with diet and age. Alteration in fatty acid composition was observed in response to dietary levels of omega-6, omega-3 and monounsaturated fatty acids, but the unsaturation index of each phospholipid remained constant for all diet treatments. These changes in lipid composition suggest that dietary fat may be a significant modulator in vivo of the physicobiochemical properties of brain synaptosomal and microsomal membranes.     

Effect of n-6 and n-3 dietary fatty acids on phospholipid composition of plasma, platelets and aorta in the rat

Female Wistar rats were fed with diets containing as dietary lipids 10% of hydrogenated coconut oil, grape-seed oil, olive oil, linseed oil and fish oil, respectively, for a period of 60 days. At the end of dietary treatment plasma, platelets and aorta phospholipids were extracted and fatty acid spectra determined. Plasma and platelet phospholipids showed the largest diet dependent changes. Anyway in aorta samples too, phospholipids showed marked increase in oleic (olive oil group) linoleic (grape-seed oil group) and alpha linoleic (linseed oil group) acids percentage. Conversely decreased amounts of arachidonic acid were detected in rats fed with diets containing linseed and fish oils. In these samples eicosapentenoic acid partly replaced arachidonic one.     

The reactivity of plasma phospholipids with lecithin:cholesterol acyltransferase is decreased in fish oil-fed monkeys

The size of low density lipoproteins (LDL) is strongly correlated with LDL cholesteryl ester (CE) content and coronary artery atherosclerosis in monkeys fed cholesterol and saturated fat. African green monkeys fed 11% (weight) fish oil diets have smaller LDL and less CE per LDL particle than lard-fed animals. We hypothesized that this might be due to a lower plasma lecithin:cholesterol acyltransferase (LCAT) activity in fish oil-fed animals. Using recombinant particles made of egg yolk lecithin-[14C]cholesterol-apoA-I as exogenous substrate, we found no difference in plasma LCAT activity (27 versus 28 nmol CE formed per h/ml) of fish oil- versus lard-fed animals, respectively; furthermore, no diet-induced difference in immunodetectable LCAT was found. However, plasma phospholipids from fish oil-fed animals were over 4-fold enriched in n-3 fatty acids in the sn-2 position compared to those of lard-fed animals. Additionally, the proportion of n-3 fatty acid-containing CE products formed by LCAT, relative to the available n-3 fatty acid in the sn-2 position of phospholipids, was less than one-tenth of that for linoleic acid. The overall rate of LCAT-catalyzed CE formation with phospholipid substrates from fish oil-fed animals was lower (5-50%) than with phospholipid substrates from lard-fed animals. These data show that n-3 fatty acids in phospholipids are not readily utilized by LCAT for formation of CE; rather, LCAT preferentially utilizes linoleic acid for CE formation. The amount of linoleic acid in the sn-2 position of plasma phospholipids is reduced and replaced with n-3 fatty acids in fish oil-fed animals. As a result, LCAT-catalyzed plasma CE formation in vivo is likely reduced in fish oil-fed animals contributing to the decreased cholesteryl ester content and smaller size of LDL particles in the animals of this diet group.     

The influence of estrogen on hepatic cholesterol metabolism and biliary lipid secretion in rats fed fish oil

Both estrogen and dietary n-3 polyunsaturated fatty acids are known to be hypocholesterolemic, but appear to exert their effects by different mechanisms. In this study, the interaction between dietary fish oil (rich in n-3 polyunsaturated fatty acids) and estrogen in the regulation of hepatic cholesterol metabolism and biliary lipid secretion in rats was studied. Rats fed a low fat or a fish oil-supplemented diet for 21 days were injected with 17alpha-ethinyl estradiol (5 mg/kg body weight) or the vehicle only (control rats) once per day for 3 consecutive days. Estrogen-treatment led to a marked reduction in plasma cholesterol levels in fish oil-fed rats, which was greater than that observed with either estrogen or dietary fish oil alone. The expression of mRNA for cholesterol 7alpha-hydroxylase was decreased by estrogen in rats fed a low fat or a fish oil-supplemented diet, while the output of cholesterol (micromol/h/kg b.wt.) in the bile was unchanged in both groups. Cholesterol levels in the liver were increased by estrogen in rats given either diet, but there was a significant shift from cholesterol esterification to cholesteryl ester hydrolysis only in the fish oil-fed animals. Estrogen increased the concentration of cholesterol (micromol/ml) in the bile in rats fed the fish oil, but not the low fat diet. However, the cholesterol saturation index was unaffected. The output and concentration of total bile acid was also unaffected, but changes in the distribution of the individual bile acids were observed with estrogen treatment in both low fat and fish oil-fed groups. These results show that interaction between estrogen-treatment and dietary n-3 polyunsaturated fatty acids causes changes in hepatic cholesterol metabolism and biliary lipid secretion in rats, but does not increase the excretion of cholesterol from the body.     

Effect of long-term feeding olive and sunflower oils on fatty acid composition and desaturation activities of liver microsomes

Changes in microsomal fatty acid composition, delta 9- and delta 6-desaturase activities and cholesterol and phosphorus liver content were studied in dogs fed olive and sunflower oil diets. No changes were observed in the saturated fatty acids between dietary groups. The level of monounsaturated fatty acids was more elevated in animals fed the OO diet, because of its high relative content in this diet although the in vitro delta 9-desaturase activity was similar in microsomes from the two groups. The proportion of arachidonic acid was similar in SO and OO fed animals. This similar level occurred despite a significant increase in the level of linoleic acid in membrane lipids as a result of feeding the SO supplement. The in vitro delta 6-desaturase activity in liver microsomes showed no differences between dogs fed the two diets. Thus, the higher desaturation presented in vivo by microsomes from OO group may be related to the inhibition by linoleic acid of delta 6-desaturase in dogs fed the SO diet. The polyunsaturated fatty acids (PUFA) from the n-3 series were higher in microsomal phosphatidylcholine and phosphatidylethanolamine from animals fed the OO supplemented diet. The cholesterol/phosphorus molar ratio was higher in the SO group in which the unsaturation index was only slightly affected in phospholipids.     

Influence of dietary lipids on the effect of chlorpromazine on membrane properties of rabbit red cells

The effect of diets containing different types of common natural oils on physical properties of red cells was investigated by using rabbits. The rabbits were fed for 18 months on a standard diet in which 8% of its energy content was provided by safflower oil and 32% energy by either more safflower oil or fish oil, linseed oil, olive oil or palm oil. Erythrocyte deformability was significantly decreased by the fish oil diet compared with each of the other diets. Osmotic fragility was significantly less (66 mM) for red cells from rabbits fed on the linseed oil diet, and significantly greater (71 mM) for red cells from rabbits on the fish oil diet, than for red cells from rabbits on the other three diets which did not differ significantly from each other (68 mM). With rabbits on the standard diet, the resistance of their erythrocytes to osmotic haemolysis was increased by chlorpromazine at concentrations below and decreased by concentrations above 30 microM. The dietary oils caused significant changes in the effects of chlorpromazine on osmotic fragility. The concentration at which the effect of chlorpromazine reversed from antihaemolytic to prohaemolytic was decreased by the safflower and linseed oil diets and increased by the fish oil diet, compared with the olive and palm oil diets. Analysis of the fatty acid compositions of the dietary oils on the one hand and of the red cell phospholipids on the other established, specifically, that in the presence of 30 microM chlorpromazine the percentage haemolysis was directly proportional to the linoleate content of the red cell phospholipids.     

Fish oil reduces cholesterol and arachidonic acid content more efficiently in rats fed diets containing low linoleic acid to saturated fatty acid ratios

Rats were fed diets containing a high level of saturated fatty acids (hydrogenated beef tallow) versus a high level of linoleic acid (safflower oil) at both low and high levels of fish oil containing 7.5% (w/w) eicosapentaenoic and 2.5% (w/w) docosahexaenoic acids for a period of 28 days. The effect of feeding these diets on the cholesterol content and fatty acid composition of serum and liver lipids was examined. Feeding diets high in fish oil with safflower oil decreased the cholesterol content of rat serum, whereas feeding fish oil had no significant effect on the cholesterol content of serum when fed in combination with saturated fatty acids. The serum cholesterol level was higher in animals fed safflower oil compared to animals fed saturated fat without fish oil. Consumption of fish oil lowered the cholesterol content of liver tissue regardless of the dietary fat fed. Feeding diets containing fish oil reduced the arachidonic acid content of rat serum and liver lipid fractions, the decrease being more pronounced when fish oil was fed in combination with hydrogenated beef tallow than with safflower oil. These results suggest that dietary n-3 fatty acids of fish oil interact with dietary linoleic acid and saturated fatty acids differently to modulate enzymes of cholesterol and fatty acid metabolism.     

Interactions of saturated, n-6 and n-3 polyunsaturated fatty acids to modulate arachidonic acid metabolism

Anti-thrombotic effects of omega-3 (n-3) fatty acids are believed to be due to their ability to reduce arachidonic acid levels. Therefore, weanling rats were fed n-3 acids in the form of linseed oil (18:3n-3) or fish oil (containing 20:5n-3 and 22:6n-3) in diets containing high levels of either saturated fatty acids (hydrogenated beef tallow) or high levels of linoleic acid (safflower oil) for 4 weeks. The effect of diet on the rate-limiting enzyme of arachidonic acid biosynthesis (delta 6-desaturase) and on the lipid composition of hepatic microsomal membrane was determined. Both linseed oil- or fish oil-containing diets inhibited conversion of linoleic acid to gamma-linolenic acid. Inhibition was greater with fish oil than with linseed oil, only when fed with saturated fat. delta 6-Desaturase activity was not affected when n-3 fatty acids were fed with high levels of n-6 fatty acids. Arachidonic acid content of serum lipids and hepatic microsomal phospholipids was lower when n-3 fatty acids were fed in combination with beef tallow but not when fed with safflower oil. Similarly, n-3 fatty acids (18:3n-3, 20:5n-3, 22:5n-3, and 22:6n-3) accumulated to a greater extent when n-3 fatty acids were fed with beef tallow than with safflower oil. These observations indicate that the efficacy of n-3 fatty acids in reducing arachidonic acid level is dependent on the linoleic acid to saturated fatty acid ratio of the diet consumed.     

Dietary oxidized cholesterol decreases expression of hepatic microsomal triglyceride transfer protein in rats

The aim of this study was to compare the effects of dietary oxidized cholesterol and pure cholesterol on plasma and very low density lipoprotein (VLDL) lipids and on some parameters of VLDL assembly and secretion in rats fed two different dietary fats. Four groups of male growing Sprague-Dawley rats were fed diets containing pure or oxidized cholesterol (5 g/kg diet) with either coconut oil or salmon oil as dietary fat (100 g/kg diet) for 35 days. Rats fed oxidized cholesterol supplemented diets had significantly lower concentrations of triglycerides and cholesterol in plasma and VLDL than rats fed pure cholesterol supplemented diets irrespective of the type of fat. In addition, rats fed oxidized cholesterol supplemented diets had significantly lower relative concentrations of microsomal triglyceride transfer protein messenger ribonucleic acid (mRNA) than rats fed pure cholesterol supplemented diets. In contrast, hepatic lipid concentrations and the relative concentration of apolipoprotein B mRNA were not influenced by the dietary factors investigated. Parameters of hepatic lipogenesis (relative mRNA concentration of sterol regulatory element binding protein-1c and activity of glucose-6-phosphat dehydrogenase) were significantly reduced by feeding fish oil compared to coconut oil, but were not affected by the type of cholesterol. In conclusion, the data of this study suggest, that dietary oxidized cholesterol affects VLDL assembly and/or secretion by reducing the synthesis of MTP but not by impairing hepatic lipogenesis or synthesis of apolipoprotein B.     

Decreased aortic early atherosclerosis and associated risk factors in hypercholesterolemic hamsters fed a high- or mid-oleic acid oil compared to a high-linoleic acid oil

Currently, diets higher in polyunsaturated fat are believed to lower blood cholesterol concentrations, and thus reduce atherosclerosis, greater than diets containing high amounts of saturated or possibly even monounsaturated fat. The present study was designed to investigate the effect of diets containing mid- or high-linoleic oil versus the typical high-linoleic sunflower oil on LDL oxidation and the development of early atherosclerosis in a hypercholesterolemic hamster model. Animals were fed a hypercholesterolemic diet containing 10% mid-oleic sunflower oil, high-oleic olive oil, or high-linoleic sunflower oil (wt/wt) plus 0.4% cholesterol (wt/wt) for 10 weeks. After 10 weeks of dietary treatment, only the animals fed the mid-oleic sunflower oil had significant reductions in plasma LDL-C levels (-17%) compared to the high-linoleic sunflower oil group. The high-oleic olive oil-fed hamsters had significantly higher plasma triglyceride levels (+41%) compared to the high-linoleic sunflower oil-fed hamsters. The tocopherol levels in plasma LDL were significantly higher in hamsters fed the mid-oleic sunflower oil (+77%) compared to hamsters fed either the high-linoleic sunflower or high-oleic olive oil. Measurements of LDL oxidation parameters, indicated that hamsters fed the mid-oleic sunflower oil and high-oleic olive oil diets had significantly longer lag phase (+66% and +145%, respectively) and significantly lower propagation rates (-26% and -44%, respectively) and conjugated dienes formed (-17% and -25%, respectively) compared to the hamsters fed the high-linoleic sunflower oil. Relative to the high-linoleic sunflower oil, aortic cholesterol ester was reduced by -14% and -34% in the mid-oleic sunflower oil and high-oleic olive oil groups, respectively, with the latter reaching statistical significance. Although there were no significant associations between plasma lipids and lipoprotein cholesterol with aortic total cholesterol and cholesterol esters for any of the groups, the lag phase of conjugated diene formation was inversely associated with both aortic total and esterified cholesterol in the high-oleic olive oil-fed hamsters (r = -0.69, P < 0.05). The present study suggests that mid-oleic sunflower oil reduces risk factors such as lipoprotein cholesterol and oxidative stress associated with early atherosclerosis greater than the typical high-linoleic sunflower oil in hypercholesterolemic hamsters. The high-oleic olive oil not only significantly reduced oxidative stress but also reduced aortic cholesterol ester, a hallmark of early aortic atherosclerosis greater than the typical high-linoleic sunflower oil.     

Effect of chronic endothelin blockade on PKC isoform distribution in mesenteric arteries from diabetic rats

Rigid plaques containing protein particles in plasma membrane build on the apical surface of the mammalian urothelium. We have previously shown that dietary fats modified the fatty acid profile as well as the fluorescence anisotropy of rat urothelial plasma membranes. In this study, we have further examined the proportion of phosphatidylcholine, phosphatidylethanolamine, cerebrosides, sulfatides and cholesterol in detergent resistant (DRM) and soluble (DSM) plasma membrane fractions as well as the properties of the particles. Four groups of weaned rats were fed for 12 weeks on a commercial diet (control), or on a formula containing 5% (w/w) of corn oil, fish oil or olein. The control DRM behaved as a distinctive domain since it was enriched in cholesterol and glycosphingolipids. DSM showed higher levels of phosphatidylcholine and phosphatidylethanolamine with respect to DRM. On the other hand, the lipid distributions were affected by the diets. Homogeneous lipid distributions between DSM and DRM were found in olein membranes, suggesting a decreased potential formation of lipid domains. In addition, properties of the uroplakins were altered by dietary treatments. Thus, uroplakins (UP) Ia, Ib, II and III observed by SDS-PAGE, were in lower proportions (mainly olein) than in controls. Moreover, a higher proportion of UPIII was cross-linked to UPIII and UPIb in olein treatment than in control. Meanwhile, only cross-linking to UPIII or UPIb was altered in corn and fish diets, respectively. These results suggest a role of the lipids in the establishment of the uroplakin interactions. Thus, specific dietary fats may have important functional implications. (Mol Cell Biochem 271: 69–75, 2005)     

Reduction of cholesterol absorption by dietary oleinate and fish oil in African green monkeys.

To determine whether diets enriched in monounsaturated or n-3 fatty acids cause a reduction in cholesterol absorption relative to those more enriched in saturated fatty acids, we measured cholesterol absorption in 18 African green monkeys fed diets enriched in lard, oleinate (oleic acid-rich safflower oil), or fish oil at two levels of dietary cholesterol (0.05 vs. 0.77 mg/kcal). All animals were initially challenged with the lard, high cholesterol diet to ascertain their responsiveness to dietary cholesterol. Based on the results of this challenge, low versus high responders were equally distributed in assignation to the low (n = 6) and high (n = 12) cholesterol regimens. Within each level of dietary cholesterol animals consumed all three dietary fats in random sequences during three experimental phases each lasting 9-12 months with a monkey chow washout period between each phase, so that each animal served as its own control. During each dietary phase measurements of plasma lipids and cholesterol absorption were performed. The animals fed the higher versus lower level of dietary cholesterol had significantly higher plasma total cholesterol and low density lipoprotein (LDL) cholesterol concentrations and lower percentage cholesterol absorption; high density lipoprotein (HDL) cholesterol levels were not affected by the level of dietary cholesterol. Dietary fish oil resulted in a 20-30% reduction (P less than 0.01) in total plasma and LDL cholesterol and a 30-40% reduction (P less than 0.01) in HDL cholesterol concentrations compared to lard and oleinate regardless of the level of dietary cholesterol. At the high level of cholesterol intake, the oleinate and fish oil diets resulted in significantly lower percentage cholesterol absorption compared to the lard fat diet (35 +/- 2%, 34 +/- 3%, 41 +/- 4%, respectively). At the lower level of dietary cholesterol, percentage cholesterol absorption values were higher than those at the high cholesterol intake (45-52% vs. 34-41%) but were not affected by the type of dietary fat. There was a significant positive correlation between plasma LDL cholesterol concentrations and percentage cholesterol absorption for the oleinate and lard diets at the high level of dietary cholesterol and a significant inverse association between plasma HDL cholesterol and percentage cholesterol absorption. We conclude that the type of dietary fat can influence cholesterol absorption in African green monkeys and that oleinate and fish oil reduce cholesterol absorption relative to lard when a high amount of cholesterol (0.77 mg/kcal) is present in the diet.     

Effect of dietary palm oil on lipoprotein lipases: lipoprotein levels and tissue lipids in rat

The aims of our study were to investigate the effect of dietary palm oil on the levels of lipoprotein lipase, hepatic lipase, fat distribution (in the aorta and liver), and total cholesterol, HDL, LDL, and triacylglycerol levels in young rats (70 g body wt) over a period of 10 weeks. Palm oil-fed rats showed higher growth rate and lower triacylglycerol levels than the control group. Hepatic lipase activity was correlated to the liver fat distribution (correlation coefficient, r = +0.682) as seen by histopathological sections and was similar for both the palm oil and the control diets. Palm oil-fed rats exhibited a significantly higher HDL cholesterol to total plasma cholesterol ratio when compared to animals fed the control diet. The triacylglycerol levels correlated inversely to the HDL cholesterol levels (r = -0.536) while the lipoprotein lipase (LPL) activity correlated directly to the LDL level (r = +0.617) for both groups of animals. The fatty acid profiles of adipose and liver tissues and plasma revealed that saturated fatty acids--palmitic and stearic--were preferentially incorporated in liver and adipose tissues and less in the plasma. This accounts for lack of deposition in the arterial wall and for the antithrombotic tendency of palm oil. Thus, our present findings suggest that dietary palm oil may not contribute to the risk for coronary heart disease.     

Interaction of dietary fat types and sesamin on hepatic fatty acid oxidation in rats

The interaction of sesamin, one of the most abundant lignans in sesame seed, and types of dietary fats affecting hepatic fatty acid oxidation was examined in rats. Rats were fed purified experimental diets supplemented with 0% or 0.2% sesamin (1:1 mixture of sesamin and episesamin), and containing 8% of either palm, safflower or fish oil for 15 days. Among the groups fed sesamin-free diets, the activity of various fatty acid oxidation enzymes was higher in rats fed fish oil than in those fed palm and safflower oils. Dietary sesamin increased enzyme activities in all groups of rats given different fats. The extent of the increase depended on dietary fat type, and a diet containing sesamin and fish oil in combination appeared to increase many of these parameters synergistically. In particular, the peroxisomal palmitoyl-CoA oxidation rate and acyl-CoA oxidase activity levels were much higher in rats fed sesamin and fish oil in combination than in animals fed sesamin and palm or safflower oil in combination. Analyses of mRNA levels revealed that a diet containing sesamin and fish oil increased the gene expression of various peroxisomal fatty acid oxidation enzymes and PEX11alpha, a peroxisomal membrane protein, in a synergistic manner while it increased the gene expression of mitochondrial fatty acid oxidation enzymes and microsomal cytochrome P-450 IV A1 in an additive manner. It was concluded that a diet containing sesamin and fish oil in combination synergistically increased hepatic fatty acid oxidation primarily through up-regulation of the gene expression of peroxisomal fatty acid oxidation enzymes.     

Phosphatidylethanolamine methyltransferase: evidence for influence of diet fat on selectivity of substrate for methylation in rat brain synaptic plasma membranes

Male weanling rats were fed diets containing 20% (w/w) fat differing in fatty acid composition for 24 days. Synaptic plasma membranes were isolated from the brain and the fatty acid composition of phosphatidylethanolamine and phosphatidylcholine was determined. In vitro assays of phosphatidylethanolamine methyl-transferase activity were performed on fresh membrane samples to assess effect of dietary fat on the rate of phosphatidylethanolamine methylation for phosphatidylcholine synthesis via the phosphatidylethanolamine methyltransferase pathway. Dietary level of n-6 and ratio of n-6 to n-3 fatty acids influenced membrane phospholipid fatty acid composition and activity of the lipid-dependent phosphatidylethanolamine methyltransferase pathway. Rats fed a diet rich in n-6 fatty acids produced a high ratio of n-6/n-3 fatty acids in synaptosomal membrane phosphatidylethanolamine, and elevated rates of methylation of phosphatidylethanolamine to phosphatidylcholine by phosphatidylethanolamine methyltransferases, suggesting that the pathway exhibits substrate selectivity for individual species of phosphatidylethanolamine containing long-chain homologues of dietary n-6 and n-3 fatty acids (20:4(n-6), 22:4(n-6), 22:5(n-6) and 22:6(n-3). It may be concluded that diet alters the membrane content of n-6, n-3 and monounsaturated fatty acids, and that change in phosphatidylethanolamine species available for methylation to phosphatidylcholine alters the rate of product synthesis in vivo by the phosphatidylethanolamine methyltransferase pathway.