Lipid composition and peroxide levels of mucosal cells in the rat large intestine in relation to dietary fat

To examine whether dietary fat alters membrane lipid composition and peroxidation of polyunsaturated fatty acids in “non-proliferative” and “proliferative” cells in the large intestine, Sprague-Dawley rats were fed diets providing a polyunsaturated-to-saturated fatty acid ratio of 1.2 or 0.3 at a high or low level of fat intake for a 25-day period. Cell populations were isolated and the effect of dietary fat on membrane polyunsaturated fatty acid content and peroxide levels was determined. Neither fat level nor fatty acid composition of diet influenced total cholesterol, total phospholipids, and percentage of phospholipid classes in membrane phospholipids. Feeding the high fat and/or high polyunsaturated-to-saturated fatty acid ratio diet increased polyunsaturated fatty acid content of mucosal cell phospholipids. Increase in polyunsaturated fatty acid content was paralleled by a decrease in the monounsaturated fatty acid content of mucosal cell phospholipids. Membrane content of total saturated fatty acids was not significantly affected by diet. Variation in phospholipid fatty acid composition between “non-proliferative” and ”proliferative” cells was observed. Lipid peroxide levels in mucosal cell lipid fractions were altered by dietary fat treatment. Animals fed high fat diets, compared to groups fed low fat diets, exhibited higher membrane peroxide levels when results are expressed as nmol/mg protein. Higher peroxide levels were observed in mucosal cells for rats fed high polyunsaturated-to-saturated fatty acid ratio diets when results were expressed per nmol of phospholipid. It is concluded that changes in fat level and fatty acid composition of the diet alters the mucosal cell membrane lipid composition in the rat large intestine and influences susceptibility of mucosal cell lipid to peroxidation. Further research is required to delineate which dietary factors—fat level, polyunsaturated-to-saturated fatty acid ratio, or both—have a primary influence on the degree of lipid peroxidation.     

The hypercholesterolemic effect of dietary coconut fatversus corn oil in hypo- or hyperresponsive rabbits is not exerted through influencing cholesterol absorption

In two inbred strains of rabbits with high or low response of plasma cholesterol to dietary saturatedversus polyunsaturated fatty acids, the efficiency of intestinal cholesterol absorption was measured. The feeding of a cholesterol-free purified diet containing saturated fatty acids in the form of coconut fat, when compared with a diet containing corn oil as polyunsaturated fatty acids, did not influence the efficiency of cholesterol absorption in the two rabbit strains. Irrespective of the dietary fat source, the hyperresponsive rabbits absorbed cholesterol more efficiently. It is concluded that the hypercholesterolemic effect of dietary coconut fatversus corn oil is not exerted by influencing cholesterol absorption.     

Comparison of the effects of dietary fish oils with different n−3 polyunsaturated fatty acid compositions on plasma and liver lipids in rats

The effects of dietary fish oils with different n−3 polyunsaturated fatty acid compositions on plasma lipid profiles in rats have been studied. Forty-eight male rats, previously maintained on a cholesterol-free diet for 15 days, were fed for 60 days with diets supplemented with 10% fat of either marine hilsa fish (Hilsa ilisa, family clupeidae) or fresh-water chital fish (Notopterus chitala, family notopteridae). The diets had similar levels of total saturated (35–41%), monounsaturated (43–47%) and n−3 polyunsaturated (9–10%) fatty acids. Cholesterol contents of the diets were adjusted to 0.85%; γ-linolenic acid (3.3%) in chital oil and eicosapentaenoic acid (4.9%) in hilsa oil diets were the major n−3 contributors. The percentage of eicosapentaenoic acid in the chital oil diet was 0.57 times that of the hilsa oil diet, but the eicosapentaenoic (EPA) to arachidonic acid (AA) ratio in the latter (4.08) was 3.2 times that of the former (1.27). Sixty days of hilsa oil diet feeding decreased the levels of cholesterol (53.3±2.9 to 50.0±1.1 mg/dL), triacylglycerol (75.7±3.8 to 64.3±2.6 mg/dL) and phospholipid (55.8±1.5 to 51.7±3.1 mg/dL) in rat plasma. Similar treatment with chital oil diet elevated the plasma cholesterol level (53.3±2.9 to 62.3±7.6 mg/dL) while triacylglycerol and phospholipid contents remained unaltered. Both the dietary treatments decreased the levels of linoleic and arachidonic acids in liver but only under the hilsa oil diet did the eicosapentaenoic acid percentage increase markedly (0.8±0.06% to 5.5±0.06%) at the expense of arachidonic acid. This study strongly suggests that the hypolipidemic effect depends on the composition of the n−3 polyunsaturated fatty acids rather than on the total n−3 polyunsaturated fatty acid content of the dietary fish oil.     

Polyunsaturated fatty acid supply with human milk

Polyunsaturated fatty acids in human milk may derive from diet, liberation from maternal body stores, or endogenous synthesis from precursor fatty acids. The contribution of each of these sources has not been studied in detail. Although maternal diet is a key factor affecting human milk composition, other factors such as gestational age, stage of lactation, nutritional status, and genetic background are known to influence the fat content and fatty acid composition in human milk. Both linoleic and α-linolenic acids, the essential fatty acids, are present in human milk, as are several other n−6 and n−3 longer chain polyunsaturated fatty acids that are required for optimal growth and development of infants. The fatty acid profile of human milk from lactating women of different countries is remarkably stable, but there is variability in some of the components, such as docosahexaenoic acid, which is mainly due to differences in dietary habits. Tracer techniques with stable isotopes have been valuable in assessing the kinetics of fatty acid metabolism during lactation and in determining the origin of fatty acids in human milk. Based on these studies, the major part of polyunsaturated fatty acids in human milk seems not to be provided directly from the diet but from maternal tissue stores.     

Effect of dietary n−3 and n−6 polyunsaturated fatty acids on lipid-metabolizing enzymes in obese rat liver

This study was designed to examine whether n−3 and n−6 polyunsaturated fatty acids at a very low dietary level (about 0.2%) would alter liver activities in respect to fatty acid oxidation. Obese Zucker rats were used because of their low level of fatty acid oxidation, which would make increases easier to detect. Zucker rats were fed diets containing different oil mixtures (5%, w/w) with the same ratio of n−6/n−3 fatty acids supplied either as fish oil or arachidonic acid concentrate. Decreased hepatic triacylglycerol levels were observed only with the diet containing fish oil. In mitochondrial outer membranes, which support carnitine palmitoyltransferase I activity, cholesterol content was similar for all diets, while the percentage of 22∶6n−3 and 20∶4n−6 in phospholipids was enhanced about by 6 and 3% with the diets containing fish oil and arachidonic acid, respectively. With the fish oil diet, the only difference found in activities related to fatty acid oxidation was the lower sensitivity of carnitine palmitoyltransferase I to malonyl-CoA inhibition. With the diet containing arachidonic acid, peroxisomal fatty acid oxidation and carnitine palmitoyltransferase I activity were markedly depressed. Compared with the control diet, the diets enriched in fish oil and in arachidonic acid gave rise to a higher specific activity of aryl-ester hydrolase in microsomal fractions. We suggest that slight changes in composition of n−3 or n−6 polyunsaturated fatty acids in mitochondrial outer membranes may alter carnitine palmitoyltransferase I activity.     

Prevention of cholesterol cholelithiasis by dietary unsaturated fats in hormone-treated female hamsters

We examined the effect of diet on gallstone incidence and the composition of biliary phosphatidylcholines in methyltestosterone-treated female hamsters. These hamsters were fed a nutritionally adequate purified lithogenic diet containing 2% corn oil, 4% butterfat, 0.3% cholesterol, and 0.05% methyltestosterone, resulting in a cholesterol gallstone incidence of 86%. This incidence was lowered when mono-and polyunsaturated fats or fatty acids were added to the diet: 2.5% oleic acid resulted in total prevention of cholesterol cholelithiasis, 2.5% linoleic acid, and 4% safflower oil (78% linoleic acid content) reduced gallstone incidence to 26 and 8%, respectively. An additional 4% butterfat (29% oleic acid content) produced gallstones in 50% of the animals. At the end of the 6-wk feeding period, the bile of all hamsters was supersaturated with cholesterol. The major biliary phosphatidylcholine species in all groups were (sn-1-sn-2): 16:0–18:2, 16:0–18:1, 18:0–18:2, 16:0–20:4, and 18:2–18:2. The safflower oil-and linoleic acidfed hamsters exhibited an enrichment of 16:0–18:2 (16–18%); added butterfat or oleic acid increased the proportion of 16:0–18:1 (9 and 25%, respectively). We conclude that the phosphatidylcholine molecular species in female hamster bile can be altered by dietary fats/fatty acids and that mono-and polyunsaturated fatty acids play a role in suppressing the induced cholelithiasis.     

The effect of dietary n−3 polyunsaturated fatty acids on HDL cholesterol in Chukot residentsvs muscovites

Native Chukot Peninsula residents, in contrast to Muscovites, consume a diet rich in n−3 polyunsaturated fatty acids. This dietary peculiarity is reflected in differences in plasma lipid and apolipoprotein contents. The Chukot residents have lower contents of total cholesterol, triglyceride, LDL (low density lipoprotein) cholesterol and apolipoprotein B, but higher HDL (high density lipoprotein) cholesterol levels than do Muscovites. The apolipoprotein A-I levels were identical in both groups. A higher HDL cholesterol to apolipoprotein A-I ratio was determined in the coastline Chukot residents (0.52±0.01) than in Muscovites (0.43±0.01; p<0.01). In contrast to Muscovites, the coastline Chukot residents also had higher n−3 and lower n−6 polyunsaturated fatty acid percentages in plasma and erythrocyte lipids, and lower phosphatidylcholine and higher sphingomyelin or phosphatidylethanolamine levels in HDL_2b and HDL₃. The higher HDL cholesterol levels in the plasma of the coastline Chukot residents appears to reflect the higher cholesterol-scavenging capacity of their HDL. We conclude from this study that the regular consumption of dietary n−3 polyunsaturated fatty acids by the coastline Chukot residents decreased LDL cholesterol transfer from plasma to peripheral cells, and enhanced cholesterol efflux from cellular membranes toward HDL.     

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.     

A preliminary study on platelet aggregation in postmenopausal women consuming extra-virgin olive oil and high-oleic acid sunflower oil

The purpose of the present study was to examine the effects of two monounsaturated fatty acid-rich oils, extravirgin olive oil (EVOO) and high-oleic sunflower oil (HOSO), on platelet aggregation in 14 postmenopausal women (aged 62.9 ± 1.8 yr) with high-fat dietary habits. Both oils contained oleic acid as the major compound (≈76% of total fatty acids), but the content of palmitic and linoleic acids and many minor compounds was significantly different. These oils were used as the only culinary fats during two 28-d periods, and represented ≈62% of the total lipid intake (≈46% of total energy consumption). Other dietary components were matched. The daily energy contribution of saturated, monounsaturated, and polyunsaturated fatty acids to the total energy consumption was 11.8, 28.5, and 2.8%, respectively, during the EVOO dietary period and 10.3, 27.8, and 4.6%, respectively, with HOSO. Aggregation in platelet-rich plasma was measured after addition of ADP. Platelet aggregation (expressed as cm/5 min) was significantly lower after the EVOO diet than after HOSO (2.1 ± 1.1 and 3.0 ± 1.4, respectively; P<0.05). Although maximal aggregation time was 40.2% higher in HOSO than in EVOO, the difference was not significant. Independent of serum cholesterol level, platelet aggregation tended to be different on the EVOO diet when women were classified according to cholesterol levels: <220 mg/dL or ≥220 mg/dL. Results suggest that other compounds present in the oils aside from the fatty acids may play an important role in modulating platelet aggregation in these postmenopausal women.     

Homeostatic control of membrane fatty acid composition in the rat after dietary lipid treatment

Diets in which both the lipid content and composition (polyunsaturated to saturated fatty acid ratio) were varied were fed to rats for 20 weeks, and the effects on the tissue lipid profiles were determined. The fatty acid profile of the plasma lipids, and the phospholipid fatty acids of the mitochondrial and microsomal fractions of liver, heart, kidney and brain, as well as erythrocyte membranes were determined. Despite large differences in the level and type of lipid present in the experimental diets and in the proportion of saturated fatty acids in the plasma lipids in response to the various diets, there was little effect on the proportion of saturated to unsaturated fatty acids in the phospholipids of the various membranes examined. The major effect of altering the dietary level of polyunsaturated to saturated fatty acids was on the ratio of the ω6/ω3 series of unsaturated fatty acids in the membrane lipids. This change occurred in all tissues except the brain, in which only a small response to altered dietary lipid intake was observed. The ω6/ω3 ratio was elevated upon feeding a diet rich in ω6 polyunsaturated fatty acids, but decreased when a diet rich in saturated fatty acids was fed. The failure to significantly alter membrane lipid saturation/unsaturation in the tissues examined would suggest that a homeostatic mechanism is operative in biological membranes and may act to buffer membranes from the effects of changes in the nature of the dietary lipid intake.     

Differential effects of dietary linoleic and α-linolenic acid on lipid metabolism in rat tissues

Comparative effects of feeding dietary linoleic (safflower oil) and α-linolenic (linseed oil) acids on the cholesterol content and fatty acid composition of plasma, liver, heart and epididymal fat pads of rats were examined. Animals fed hydrogenated beef tallow were used as isocaloric controls. Plasma cholesterol concentration was lower and the cholesterol level in liver increased in animals fed the safflower oil diet. Feeding the linseed oil diet was more effective in lowering plasma cholesterol content and did not result in cholesterol accumulation in the liver. The cholesterol concentration in heart and the epididymal fat pad was not affected by the type of dietary fatty acid fed. Arachidonic acid content of plasma lipids was significantly elevated in animals fed the safflower oil diet and remained unchanged by feeding the linseed oil diet, when compared with the isocaloric control animals fed hydrogenated beef tallow. Arachidonic acid content of liver and heart lipids was lower in animals fed diets containing safflower oil or linseed oil. Replacement of 50% of the safflower oil in the diet with linseed oil increased α-linolenic, docosapentaenoic and docosahexaenoic acids in plasma, liver, heart and epididymal fat pad lipids. These results suggest that dietary 18∶2ω6 shifts cholesterol from plasma to liver pools followed by redistribution of 20∶4ω6 from tissue to plasma pools. This redistribution pattern was not apparent when 18∶3ω3 was included in the diet.     

Dietary fat composition and tocopherol requirement: IV. Safety of polyunsaturated fats

In a long-term multigeneration study, conducted in our laboratories for 32-years, with occasional longevity and histopathological evaluations included, rats of our own inbred strain (originally of Wistar derivation) were fed semisynthetic diets comprising whole wheat, skim milk powder, and fat in the form of margarine products. The total source of tocopherols was the dietary fat itself. Saturated fatty acid content (S) remained relatively constant at about 20% of the fat and total tocopherol level also remained constant at about 0.12% of the fat. Polyunsaturated fatty acid (P) content, however, progressively increased almost fourfold, from 7.5% to 28.5% and alphatocopherol levels decreased to one-half level, from 0.033% to 0.016% of the fat. Hence, the ratio of polyunsaturated fatty acids to alpha-tocopherol content changed markedly from 227∶1 to 1780∶1, with other factors (relative to fat composition) held constant during the 32-year period of feedings and observations. Fat level in the diet increased over the years from 9.2% to 16.0% or from about 21% to about 33% of the caloric intake. Thus, quality and quantity of the fat in the diet progressively changed, and the impact of these changes was evaluated by comparing biological performances of the successive generations. Growth and reproduction and lactation performances were noted to be regularly satisfactory and comparable from generation to generation throughout the experimental period. Longevity studies conducted on arbitrarily selected generations also provided data showing no deleterious effects associated with a dietary change. Histopathological examinations of tissue revealed minimal myocarditis and no malignant tumors which could be attributed to a dietary factor. No vitamin E deficiencies were observed. Even the in vitro peroxide hemolysis values for the red blood cells of the animals, fed the diets containing the higher levels of polyunsaturated fatty acids, were low, indicating that the dietary fats provided sufficient absorbable tocopherol to protect the potentially oxidizable unsaturated fatty acids in the erythrocyte membrane. Biochemical data reflected responses to aging and not to any specific diet fed. It is concluded that a diet providing as much as 33% of the calories as a fat, the latter containing up to 28.5% polyunsaturated fatty acids, substantially of the essential fatty acid type, with a P/S ratio of up to 1.6∶1 and a polyunsaturated fatty acid to alphatocopherol ratio as high as 1780∶1] produces no undesirable effects in the rat. Presented in part at a symposium entitled “Long Term Nutritional Effects of Dietary Fats” at the International Society for Fat Research World Congress, September 30, 1970, Chicago, Illinois.     

Isomeric fatty acids: Evaluating status and implications for maternal and child health

“Isomeric fatty acids” is a term that refers to the trans- and positional isomers formed during hydrogenation of naturally occurring oils. The purposes of this paper are as follows: (i) to summarize potential exposure of infants to isomeric fatty acids by reviewing estimates of isomeric fatty acids in the maternal diet, in human milk, and in infant formula/infant foods, and (ii) to evaluate the evidence for adverse effects of isomeric fatty acids on infant development with respect to growth and essential fatty acid status. Estimates of the intake of trans-fatty acids vary widely both within and across populations. Current estimates of trans-fatty acids in the North American population are 4–11% of total fatty acids or 3–13 g/(person·d), whereas in Mediterranean countries in which olive oil is the primary fat and in Far Eastern countries in which little commercially hydrogenated fat is consumed, per capita consumption of trans-fatty acids is <1–2 g/d. The trans-fatty acid content of human milk reflects the cross-cultural variation in the maternal diet, with trans-fatty acids in human milk samples ranging from 6 to 7% in North America to <0.5% in Hong Kong. Trans-fatty acids are transferred from the maternal diet through the placenta to the developing fetus or through milk to the breast-fed infant. In some studies, plasma trans-fatty acids are inversely related to birth weight and head circumference. The hypothesis that dietary trans-fatty acids could inhibit biosynthesis of long-chain polyunsaturated fatty acids with 20 and 22 carbon atoms and thus affect infant development is supported by studies demonstrating an inverse correlation of plasma trans-fatty acids with n−3 and n−6 long-chain polyunsaturated fatty acids in infants. However, no such relationship has been observed in human milk. A definitive answer concerning a potentially adverse effect of dietary trans-fatty acids on infant development awaits future studies.     

Dietary saturated fat level alters the competition between α-linolenic and linoleic acid

Male weanling rats were fed semi-synthetic diets high in saturated fat (beef tallow) vs high in linoleic acid (safflower oil) with or without high levels of α-linolenic acid (linseed oil) for a period of 28 days. The effect of feeding these diets on cholesterol content and fatty acid composition of serum and liver lipids was examined. Feeding linseed oil with beef tallow or safflower oil had no significant effect on serum levels of cholesterol. Serum cholesterol concentration was higher in animals fed the safflower oil diet than in animals fed the beef tallow diet without linseed oil. Feeding linseed oil lowered the cholesterol content in liver tissue for all dietary treatments tested. Consumption of linseed oil reduced the arachidonic acid content with concomitant increase in linoleic acid in serum and liver lipid fractions only when fed in combination with beef tallow, but not when fed with safflower oil. Similarly, ω3 fatty acids (18∶3ω3, 20∶5ω3, 22∶5ω3, 22∶6ω3) replaced ω6 fatty acids (20∶4ω6, 22∶4ω6) in serum and liver lipid fractions to a greater extent when linseed oil was fed with beef tallow than with safflower oil. The results suggest that the dietary ratio of linoleic acid to saturated fatty acids or of 18∶3ω3 to 18∶2ω6 may be important to determine the cholesterol and arachidonic acid lowering effect of dietary α-linolenic acid.     

A new relationship between total/high density lipoprotein cholesterol and polyunsaturated fatty acids

Dietary and plasma fatty acids have been linked to total cholesterol but not to the ratio of total/high-density lipoprotein cholesterol (TC/HDLC). To evaluate the relationship between dietary and plasma levels of polyunsaturated fatty acids (PUFA) and TC/HDLC, we analyzed cross-sectional and longitudinal data using 519 plasma samples (50% men, 50% women) from subjects participating in the Framingham Heart Study and results from a study feeding diets rich in either n-6 linoleic acid or n-3 α-linolenic acid with or without fish oil supplements (n-3 derivatives). Values of TC/HDLC are inversely related to the percent of plasma PUFA when both variables are measured at the same time in different subjects,R=0.82,P<0.000001. PUFA in phospholipids increase in response to increased dietary intake of different PUFA, either n-3 or n-6 or fish oils. There was a highly significant inverse relationship between TC/HDLC and the percent of PUFA in phospholipids,R=0.97,P<0.001. The relationship was similar regardless of the source and type of dietary fatty acids. A similar relationship existed when only the baseline points were considered. When plasma PUFA % increases, either in response to a diet high in PUFA or across different subjects, TC/HDLC ratios decline. Evaluation of plasma fatty acid profiles and increased balanced dietary intake of PUFA to bring fatty acid profiles of subjects with low PUFA plasma levels closer to the profile of a healthy reference group is an effective approach to reduce high TC/HDLC. Reductions of more than 50% in TC/HDLC appear feasible with dietary modification alone. Further research into fatty acid metabolic activity may determine the biochemical basis of common dysplipidemias.     

Quantitative effects of dietary polyunsaturated fats on the composition of fatty acids in rat tissues

A method combining data on fatty acid composition into subsets is used to illustrate general relative competitive selectivities in the metabolic and transport events that maintain fatty acid compositions in tissue lipids and to minimize differences among tissues or species in the amount of individual fatty acids. Fatty acid compositions of triglycerides and phospholipids in several tissues of the rat were maintained with simple relationships between the exogenous n−3 and n−6 dietary polyunsaturated fatty acids and the endogenous n−7 and n−9 types of fatty acid. The general pattern of fatty acids in triglycerides was similar for liver, plasma and adipose tissue, averaging about 30% as saturated acids, 67% as 16- and 18-carbon unsaturated acids and only about 2% as 20- and 22-carbon highly unsaturated acids. The tissues maintained a linear relationship between the amount of 18-carbon polyunsaturated fatty acids in the diet and in the tissue triglycerides, with the proportionality constant for 18∶3n−3 being 60% of that for 18∶2n−6. The total phospholipids of liver, plasma and red blood cells maintained about 45% of the fatty acids in the form of saturated fatty acids and 20–30% as 20- and 22-carbon highly unsaturated fatty acids irrespective of very different proportions of n−3, n−6 and n−9 types of fatty acids. In all three tissues, the 20-carbon highly unsaturated fatty acids of the n−3, n−6 and n−9 type were maintained in a competitive hyperbolic relationship with apparent EC₅₀ values for dietary 18∶2n−6 and 18∶3n−3 near 0.1% of dietary calories. The consistent quantitative relationships described in this study illustrate an underlying principle of competition among fatty acids for a limited number of esterification sites. This approach may be useful in predicting the influence of diet upon tissue levels of the substrates and antagonists of eicosanoid biosynthesis.     

Influence of dietary fat composition on intestinal absorption in the rat

Omega-3 fatty acids influence the function of the intestinal brush border membrane. For example, the omega-3 fatty acid eicosapentaenoic acid (20∶5ω3) has an antiabsorptive effect on jejunal uptake of glucose. This study was undertaken to determine whether the effect of feeding α-linolenic acid (18∶3ω3) or EPA plus docosahexaenoic acid (22∶6ω3) on intestinal absorption of nutrients was influenced by the major source of dietary lipid, hydrogenated beef tallow or safflower oil. Thein vitro intestinal uptake of glucose, fatty acids and cholesterol was examined in rats fed isocaloric diets for 2 weeks: beef tallow, beef tallow + linolenic acid, beef tallow + eicosapentaenoic acid/docosahexaenoic acid, safflower oil, safflower oil + linolenic acid, or safflower oil + eicosapentaenic acid/docosahexaenoic acid. Eicosapentaenoic acid/docosahexaenoic acid reduced jejunal uptake of 10 and 20 mM glucose only when fed with beef tallow, and not when fed with safflower oil. Linolenic acid had no effect on glucose uptake, regardless of whether it was fed with beef tallow or safflower oil. The jejunal uptake a long-chain fatty acids (18∶0, 18∶2ω6, 18∶3ω3, 20∶4ω6, 20∶5ω3 and 22∶6ω3) and cholesterol was lower in salfflower oil than with beef tallow. When eicosapentaenoic acid/docosahexaenoic acid was given with beef tallow (but not with safflower oil), there was lower uptake of 18∶0, 20∶5ω3 and cholesterol. The demonstration of the inhibitory effect of linolenic acid or eicosapentaenoic acid/docosahexaenoic acid on cholesterol uptake required the feeding of a saturated fatty acid diet (beef tallow). These changes in uptake were not explained by differences in the animals’ food intake, body weight gain or intestinal weight. Feeding safflower oil was associated with an approximately 25% increase in the jejunal and ileal mucosal surface area, but this increase was prevented by combining linolenic acid or eicosapentaenoic acid/docosahexaenoic acid with safflower oil. Different inhibitory patterns were observed when mixtures of fatty acids were present together in the incubation medium, rather than in the diet: for example, when 18∶0 was in the incubation medium with 20∶4ω6, the uptake of 20∶4ω6 was reduced, whereas the uptake was unaffected by 18∶2ω6 or 20∶5ω3. Thus, (1) the inhibitory effect of eicosapentaenoic acid/docosahexaenoic acid on jejunal uptake of glucose, fatty acids and cholesterol was influenced by the major dietary lipid, saturated (beef tallow) or polyunsaturated fatty acid (safflower oil); and (2) different omega-3 fatty acids (linolenic acid versus eicosapentaenoic acid/docosahexaenoic acid) have a variable influence on the intestinal absorption of nutrients.     

Short Chain Saturated Fatty Acids Decrease Circulating Cholesterol and Increase Tissue PUFA Content in the Rat

This study investigates the effect of various dietary saturated fatty acid (SFA) profiles on plasma lipid parameters and tissue fatty acid composition in rats. The experiment was designed to monitor polyunsaturated fatty acids (PUFA) levels, while examining different amounts and types of SFA. Four isocaloric diets were prepared, containing 10–11 mol% of fatty acids (FA) as linoleic acid (LNA) and 2.5 mol% as α-linolenic acid (ALA), leading to an identical and well-balanced LNA/ALA ratio. The initial rapeseed oil/corn oil mixture providing ALA and LNA was enriched with olive oil to prepare the olive oil diet. The butterfat diet was supplemented with butterfat, containing short-chain SFA (C4:0–C10:0, 17 mol% of FA), lauric acid (C12:0, 3.2 mol%), myristic acid (C14:0, 10.5 mol%) and palmitic acid (C16:0, 14.5 mol%). The saturates diet was supplemented with trilaurin, trimyristin and tripalmitin to obtain the same level of lauric, myristic and palmitic acids as the butterfat diet, without the short-chain SFA. The trimyristin diet was enriched with trimyristin only. The results showed that the butterfat diet contributed to specific effects, compared to the olive oil diet and the saturates and trimyristin diets: a decrease in plasma total, LDL- and HDL-cholesterol, higher tissue storage of ALA and LNA, and a higher level of (n-3) highly unsaturated fatty acids in some tissues. This study supports the hypothesis that in diets with identical well-balanced LNA/ALA ratios, short chain SFA may decrease circulating cholesterol and increase tissue polyunsaturated fatty acid content in the rat.     

Dietary α-linolenic acid lowers postprandial lipid levels with increase of eicosapentaenoic and docosahexaenoic acid contents in rat hepatic membrane

This study was designed to examine the effects of dietary n−3 and n−6 polyunsaturated fatty acids (PUFA) on postprandial lipid levels and fatty acid composition of hepatic membranes. Male Sprague-Dawley rats were trained for a 3−h feeding protocol and fed one of five semipurified diets: one fat-free diet or one of four diets supplemented with 10% (by weight) each of corn oil, beef tallow, perilla oil, and fish oil. Two separate experiments were performed, 4-wk long-term and 4-d short-term feeding models, to compare the effects of feeding periods. Postprandial plasma lipid was affected by dietary fats. Triacylglycerol (TG) and total cholesterol levels were decreased in rats fed perilla oil and fish oil diets compared with corn oil and beef tallow diets. Hepatic TG and total cholesterol levels were also reduced by fish oil and perilla oil diets. Fatty acid composition of hepatic microsomal fraction reflected dietary fatty acids and their metabolic conversion. The major fatty acids of rats fed the beef tallow diet were palmitic, stearic, and oleic. Similarly, linoleic acid (LA) and arachidonic acid in the corn oil group, α-linolenic acid (ALA) and eicosapentaenoic acid (EPA) in the perilla oil group, and palmitic acid and docosahexaenoic acid (DHA) in the fish oil group were detected in high proportions. Both long- and short-term feeding experiments showed similar results. In addition, microsomal DHA content was negatively correlated with plasma lipid levels. Hepatic lipid levels were also negatively correlated with EPA and DHA contents. These results suggest that n−3 ALA has more of a hypolipidemic effect than n−6 LA and that the hypolipidemic effect of n−3 PUFA may be partly related to the increase of EPA and DHA in hepatic membrane.     

Dietary cholesterol modulates Δ6 and Δ9 desaturase mRNAs and enzymatic activity in rats fed a low-EFA diet

The effects of a 1% addition of cholesterol to a diet low in EFA on FA desaturases were examined. The administration of cholesterol markedly increased the esterified cholesterol content in microsomes and total liver lipids from the first day, whereas the proportion of free cholesterol remained unaltered throughout the treatment. An excellent homeostasis in the free cholesterol content was apparently evoked by the acyl-CoA cholesterol acyltransferase. The cholesterol esters were mainly oleate, palmitate, and stearate, and the addition of cholesterol increased the relative proportions of cholesterol palmitoleate and oleate. The addition of cholesterol to a low-EFA diet induced, as in animals fed a high-FFA diet, a marked increase in liver stearoyl-CoA desaturase-1 mRNA and enzyme activity. This increased activity apparently evoked a similar enhancement of palmitoleic and oleic acids in total and microsomal liver lipids. The cholesterol-rich diet depressed the liver Δ6 and Δ5 desaturase activity. However, the abundance of Δ6 desaturase mRNA was not modified throughout the treatment. This indicates that the depressive effect is evoked at a step beyond that controlled by the mRNA level. The depression of both enzymatic activities was consistent with the decrease in the percentages of arachidonic acid and DHA in total and microsomal liver lipids. Taken together, these results indicate that through its modulating effect on the desaturases, dietary cholesterol may lead an animal or humaan fed low-EFA diet to a true deficiency by the decreased synthesis of the highly polyunsaturated acids derived from linoleic and α-linolenic acids.