Effects of dietary alpha- and gamma-linolenic acid on lipid metabolism in young and adult rats

The effect of age on lipid metabolism was studied in rats fed diets containing safflower oil (SFO, 78% linoleic acid), evening primrose oil (EPO, 9.4% gamma-linolenic acid and 70% linoleic acid) or the mixture of safflower and linseed oil (SLO, 10.2% alpha-linolenic acid and 68% linoleic acid). The activity of hepatic HMG-CoA reductase declined with age in all groups. In adult rats, the reductase activity was high in the EPO group and low in the SLO group. The activity of hepatic cholesterol 7 alpha-hydroxylase was independent of the diet or age. Hepatic delta 6-desaturase activity was low in adult rats fed EPO. In liver microsomal phospholipids, the percentage of 22:5 n-6 decreased while that of 22:6 n-3 increased with age. The ratio of linoleate metabolites to linoleate was high in the EPO group and low in the SLO group. Liver and serum cholesterol increased with age only in rats fed the SLO diet. Thus, the results indicated an enhanced susceptibility to dietary fats with age.     

Dietary trans-fatty acids alter adipocyte plasma membrane fatty acid composition and insulin sensitivity in rats

The present study was designed to investigate the effects of dietary trans-fatty acids (TFA) present in Indian vanaspati (partially hydrogenated vegetable oils) in comparison with saturated fatty acids (SFA) on adipocyte plasma membrane fatty acid composition, fluidity, and insulin action. The effects of 3% energy (% en) TFA was studied at 2% and 4% en of linoleic acid (18:2 n-6). WNIN male weanling rats were divided into 4 groups and fed casein-based diet containing 10% groundnut oil control (CON), palmolein (SFA), blend of vanaspati and safflower oil (3% en TFA and 2% en 18:2 n-6, TFA-1), or blend of vanaspati and safflower oil (3% en TFA and 4% en 18:2 n-6, TFA-2) for 12 weeks. Compared with CON, rats fed TFA and SFA diets had high levels of fasting plasma insulin and triglycerides. Both TFA- and SFA-fed groups had low levels of arachidonic acid (20:4 n-6) in adipocyte plasma membrane phospholipids. However, adipocyte plasma membrane fluidity decreased only in TFA-fed rats. Norepinephrine-stimulated lipolysis was high, whereas the antilipolytic effect of insulin and insulin-stimulated glucose transport were low in the adipocytes of SFA- and TFA-fed rats. However, the extent of decrease in the antilipolytic effect of insulin and insulin-stimulated glucose transport was greater in TFA-fed rats. These findings suggest that diet providing approximately 10% en SFA (PUFA/SFA [P/S] ratio 0.2) decreased adipocyte insulin sensitivity in rats. In these diets, replacement of approximately 2% en SFA (16:0) and approximately 1% en monounsaturated fatty acid (18:1 cis) with TFA decreased adipocyte insulin sensitivity to a greater extent. However, increasing dietary 18:2 n-6 did not prevent or reduce the TFA-induced adipocyte insulin resistance.     

Brain Membrane Sensitivity to Ethanol during Development of Functional Tolerance to Ethanol in Rats

Adult male rats were rendered progressively tolerant to ethanol by daily intragastric administration of doses of 3-6 g/kg body weight. Functional tolerance assessed by the hypothermic effect after injection of a challenge dose of ethanol developed slowly and was demonstrable after 2 weeks of treatment. Intrinsic crude synaptosomal membrane fluidity, as assessed by fluorescence polarization of DPH, as well as (Na+ + K+)ATPase activity, did not change significantly during the whole treatment. However, the extra addition of ethanol (0.175-0.700 M) in vitro to the membranes of rats, having received ethanol over a period of at least 2 weeks, fluidized less and inhibited the (Na+ + K+)ATPase activity less than in starch-fed controls. The time-course for the appearance of this membrane hyposensitivity was found to be the same as the time course for the development of functional tolerance to ethanol. The correlation between the degree of functional tolerance and the (Na+ + K+)ATPase sensitivity to ethanol appeared very significant, highlighting the sensitivity of membrane-bound enzymes to detecting adaptive changes in complex biological membranes tolerance.     

Effects of Acute and Chronic Ethanol Exposure on Intestinal Microvillus Membrane Lipid Composition and Fluidity

Chronic ethanol consumption produces nutrient malabsorption. The mechanisms by which this occurs are poorly understood. One potential mechanism is an alteration in microvillus membrane (MVM) composition and fluidity. The effects of in vivo ethanol exposure on MVM lipid composition and fluidity were determined in rats fed either a standard diet or 15% ethanol in water for 2 months. Acute jejunal exposure to 4% ethanol was also performed in vivo in each feeding group. Acute exposure to ethanol produced an increase in static and dynamic membrane fluidity associated with a decrease in MVM cholesterol regardless of prior ethanol exposure. Chronic ethanol feeding alone did not alter membrane fluidity. Changes in membrane fatty acid composition were minor and variable after both acute and chronic ethanol exposure. Prior chronic ethanol feeding did not prevent the acute effects of ethanol on MVM composition or fluidity. These data support the theory that ethanol acutely disrupts nutrient transport by changing MVM lipid fluidity. The absence of adaptive changes in membrane composition and fluidity may also explain the persistent absorptive defects seen with chronic alcoholism.     

Effect of the linolenic acid content of the mother's diet on the polyunsaturated fatty acid composition of subcellular fractions in brain development in the rat

In order to determine precisely the respective roles of linolenic acid and linoleic acid in the maternal diet on rat brain subcellular fractions during development, we used two diets with different percentages of linolenic acid (18:3 n-3). The animals were fed peanut oil (group A) or soybean oil (group B) during pregnancy and throughout lactation. Nature and amount of essential fatty acids had no incidence on saturated and monounsaturated fatty acid distributions in myelin, synaptosomal, mitochondrial and microsomal fractions. In adult rats, all subcellular fractions are marked by an increase of n-3 fatty acid and a decrease of n-6 fatty acid levels in group B compared to group A. In 15-day-old animals, on the contrary, only the synaptosomal fractions are significantly affected by the diet. Independent of diet, brain development is marked by a decrease of n-6 fatty acids in all subcellular fractions; on the other hand, the n-3 fatty acid level is increased in the synaptosomal and mitochondrial fractions, and decrease in the myelin and microsomal fractions. The sum of (n-3 + n-6) fatty acids remains constant in group B and in group A in all subcellular fractions. Finally, under our experimental conditions, we found no marked effect of diet composition upon linoleic acid conversion to arachidonic acid; only the delta 4-7-10-13-16-docosapentaenoic acid (22:5 n-6) level decreased in group B. delta 7-10-13-16-19-Docosapentaenoic acid (22:5 n-3) seemed to be a better substrate for delta 4 desaturase than delta 7-10-13-16-docosatetraenoic acid (22:4 n-6).     

High-fat diet-induced hyperglycemia and obesity in mice: Differential effects of dietary oils

Mice fed a high-fat diet develop hyperglycemia and obesity. Using non-insulin-dependent diabetes mellitus (NIDDM) model mice, we investigated the effects of seven different dietary oils on glucose metabolism: palm oil, which contains mainly 45% palmitic acid (16:0) and 40% oleic acid (18:1); lard oil, 24% palmitic and 44% oleic acid; rapeseed oil, 59% oleic and 20% linoleic acid (18:2); soybean oil, 24% oleic and 54% linoleic acid; safflower oil, 76% linoleic acid; perilla oil, 58% α-linolenic acid; and tuna fish oil, 7% eicosapentaenoic acid and 23% docosahexaenoic acid. C57BL/6J mice received each as a high-fat diet (60% of total calories) for 19 weeks (n = 6 to 11 per group). After 19 weeks of feeding, body weight induced by the diets was in the following order: soybean> palm ≥ lard ≥ rapeseed ≥ safflower ≥ perilla> fish oil. Glucose levels 30 minutes after a glucose load were highest for safflower oil (21.5 mmol/L), modest for rapeseed oil, soybean oil, and lard ( 17.6 mmol/L), mild for perilla, fish, and palm oil ( 13.8 mmol/L), and minimal for high-carbohydrate meals ( 10.4 mmol/L). Only palm oil-fed mice showed fasting hyperinsulinemia (P < .001). By stepwise multiple regression analysis, body weight (or white adipose tissue [WAT] weight) and intake of linoleic acid (or n-3/n-6 ratio) were chosen as independent variables to affect glucose tolerance. By univariate analysis, the linoleic acid intake had a positive correlation with blood glucose level (r = .83, P = .02) but not with obesity (r = .46, P = .30). These data indicate that (1) fasting blood insulin levels vary among fat subtypes, and a higher fasting blood insulin level in palm oil-fed mice may explain their better glycemic control irrespective of their marked obesity; (2) a favorable glucose response induced by fish oil feeding may be mediated by a decrease of body weight; and (3) obesity and a higher intake of linoleic acid are independent risk factors for dysregulation of glucose tolerance.     

Effects of dietary sunflowerseed oil and marine oil on platelet membrane fluidity, arterial thrombosis, and platelet responses in rats

The relationships among platelet membrane fluidity, arterial thrombosis tendency, and platelet aggregation and prostanoid formation were investigated after feeding rats diets enriched in (n-6) or (n-3) polyunsaturated fatty acids. For at least 8 weeks, rats were fed a control diet containing 5 energy % (en%) sunflowerseed oil, a diet high in sunflowerseed oil (50 en%) which contains large amounts of 18:2(n-6), or a diet high in marine oil (5 en% sunflowerseed oil plus 45 en% sperm-whale oil) which contains considerable amounts of 20:5(n-3) and its desaturation and elongation products. Compared with the control diet, platelet membrane fluidity, measured by fluorescence polarization using platelets labelled with 1,6-diphenyl-1,3,5-hexatriene, was significantly increased upon feeding of the sunflowerseed-oil diet or the marine-oil diet. Both of these diets lowered arterial thrombosis tendency, measured by Hornstra's loop technique. Aggregation of platelets in whole blood activated with collagen tended to be higher upon sunflowerseed-oil feeding and lower in the marine-oil group. The concomitant formation of thromboxane A2 was not altered in the sunflowerseed-oil group, but was significantly reduced upon feeding the marine-oil diet. The results indicate that an increase in platelet membrane fluidity may be associated with a reduction in arterial thrombosis tendency. With the techniques used, no direct relationship could be observed among platelet membrane fluidity, platelet aggregation and platelet prostanoid production.     

Fatty acid and enzymatic compositional changes in the pancreas of rats fed dietary n-3 and n-6 polyunsaturated fatty acids

The influence of n-3 and n-6 PUFA on the fatty acid composition and the enzyme content of zymogen granules of the normal exocrine pancreas was tested on rats. The animals were fed on different diets comprising 5% fish oil (FO), safflower oil (SFO), and evening primrose oil (EPO) used singly or in combination as dietary fats. The results were compared with those from animals fed 5% hydrogenated beef tallow (HBT). The fatty acid composition and digestive enzyme content were analyzed after a 6-wk feeding period. Differences in the pancreatic fatty acid profiles were related to the fatty acid composition of the ingested fats. Equivalent levels of n-3 fatty acids and 20:3n-6 were obtained with either EPO or FO fed singly or in combination. Similar results were observed with SFO/FO. Higher C20:3n-6/C20:4n-6 ratios were obtained with the oil mixtures. An increase in amylase levels, but a decrease in serine protease (Band 21 kdalton) levels, was associated with EPO. An elevation in procarboxypeptidase levels paralleled an increase in 18:0 levels, whereas the proportion of lipase (Band 49 kdalton) varied inversely with the proportion of C20:3n-6. The SFO/FO mixture elevated the proportions of protease II and proelastase. These results suggest that specific fatty acids influence the proportion of specific digestive enzymes in the zymogen granules.     

Influence of different dietary fatty acid sources on erythrocyte lipids and plasma and liver essential fatty acids in hamsters fed ethanol

Hamsters fed ethanol were given three different dietary sources of essential fatty acids; safflower oil, evening primrose oil (both mainly n-6 fatty acids) or linseed oil (mainly n-3 fatty acids). After 7 weeks, plasma, erythrocyte and liver lipids and fatty acids were analyzed. Plasma and liver lipids were not significantly different in the ethanol-fed hamsters compared to the controls. Erythrocyte total phospholipid was increased only in the ethanol-fed groups given n-6 but not n-3 fatty acids. Some fatty acid changes induced by ethanol were predictable, e.g. lower 20:4 n-6 in hamsters fed n-6 fatty acids, but others were not predictable, e.g. higher 22:6 n-3 in all the ethanol-fed groups. The effect of ethanol on hamster lipids and fatty acid composition appears dependent on the predominant class of dietary fatty acids.     

Specific alterations in different adipose tissues of pig adipocyte plasma membrane structure by dietary lipids

The effect of dietary n-6 polyunsaturated fatty acid content on pig adipocyte plasma membrane was studied with two types of adipose tissues: subcutaneous backfat layer and perirenal fat. When pigs were fed a diet containing 15 percent sunflower oil, the n-6 polyunsaturated fatty acid content in the membranes increased in both tissues parallel to a decrease in the n-9 monounsaturated fatty acid content. An increase in membrane fluidity measured by fluorescence polarization was observed particularly in subcutaneous tissue, in spite of a higher level of some membrane rigid components: the sphingomyelin/phosphatidylcholine ratio was increased in the subcutaneous tissue, whereas the cholesterol/phospholipid ratio was increased in the perirenal one. The latter results gave evidence for a depot-dependent modification in the membrane structure by dietary lipids.     

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.     

Influence of highly purified eicosapentaenoic acid ethyl ester on insulin resistance in the Otsuka Long-Evans Tokushima Fatty Rat, a model of spontaneous non-insulin-dependent diabetes mellitus

We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid derived from fish oil, in comparison to the effects of lard, olive oil, safflower oil, or distilled water as the control on the development of insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of spontaneous non—insulin-dependent diabetes mellitus (NIDDM) with obesity. After 17 or 18 weeks of treatment, the glucose infusion rate (GIR) in the euglycemic insulin-glucose clamp test only showed a significant increase in EPA-E-treated rats compared with control rats given distilled water alone as the vehicle. The GIR in EPA-E-treated animals was approximately three times greater than in the controls. This is the first report to display the influence of various fatty acids on the development of insulin resistance in OLETF rats. We demonstrated that EPA-E prevents the onset of insulin resistance, whereas olive oil and safflower oil have no effect and lard exacerbates insulin resistance. Fatty acid analysis of phospholipids in skeletal muscle showed a significant increase of the C18:2, C20:5, and C22:5 components in EPA-E-treated rats and, conversely, a significant decrease in C20:4. In addition, EPA-E-treated rats showed a significant increase in GLUT4 mRNA in skeletal muscle when compared with control rats. Our results indicate that the beneficial effect of EPA-E on insulin resistance in OLETF rats is likely to be dependent on modification of the phospholipid components of the skeletal muscle membrane. These findings suggest that dietary fatty acids may play a key role in the development of insulin resistance in patients with NIDDM.     

Energy restriction dilutes the changes related to dietary fat type in membrane phospholipid fatty acid composition in rats

To investigate liver cell membrane phospholipid (PL) fatty acid (FA) composition in response to the consumption of different types of dietary fat and graded levels of energy intake, rats were fed for 10 weeks on a diet containing either fish oil, safflower oil, or beef tallow. Within each dietary fat group, subgroups were either provided free access to food or energy-restricted to 85% or 70% of the ad libitum intake by reducing the dietary carbohydrate content while keeping other macronutrient intakes constant. Higher (P < .05) proportions of docosahexaenoic acid, linoleic acid, and monounsaturated FA were observed in the membrane PL of the fish oil, safflower oil, and beef tallow groups, respectively, resembling the FA composition in the diets. However, such modifications of dietary FA composition in, membrane PL FA were influenced by body energy status. The higher docosahexaenoic acid and total n-3 FA content in phosphatidylcholine (PC), sphingomyelin (SPH), and phosphatidylserine (PS) of the ad libitum fish oil group compared with the other dietary groups no longer existed when energy supply was restricted. Therefore, reducing energy intake tended to dilute the changes of membrane PL FA composition occurring as a function of dietary FA composition. These data suggest that the influence of dietary fat type on cellular structure and perhaps function becomes increasingly important with progressively positive energy balance.     

Effects of Prenatal Ethanol and Long-Chain n-3 Fatty Acid Supplementation on Development in Mice. 2. Fatty Acid Composition of Brain Membrane Phospholipids

Pregnant mice were fed equivalent daily amounts of a liquid diet containing 25% (kcal) ethanol, or with maltose dextrin substituted isocalorically for ethanol. The diet also contained 20% oil; this was either of two mixtures, one comprised of predominantly n-6 (18:2n-6) fatty acids, and the other containing an equivalent amount of n-6, but supplemented with a source of long chain n-3 (20:5n-3, 22:6n-3) fatty acids. An additional control group was fed lab chow ad libitum. The treatment was implemented from day 7 to 17 of gestation, whereafter all groups were fed lab chow. Birth occurred on day 19, and the fatty acid composition of the brain membrane phospholipids was determined in the pups 3 days after birth (day 22 postconception) and again, 10 days later (day 32 postconception). On day 22 the polyunsaturated fatty acid (PUFA) composition of the brain phospholipids reflected dietary availability, with the n-3/n-6 ratio higher in the n-3 groups; this was decreased by ethanol in the phosphatidylcholine (PC) fraction. The dietary effect was still apparent on day 32; again ethanol reduced this in both the PC and phosphatidylethanolamine (PE) fractions. The n-3 oil, but not ethanol, increased the 20:3n-6/20:4n-6 ratio, indicative of an inhibition of the activity of delta-5 desaturase. With respect to the 22:C compounds, the n-3 oil decreased the levels of 22:5n-6, while increasing those of 22:6n-3, but generally the sum of these two fatty acids remained unchanged. Ethanol decreased levels of 22:5n-6, and, on day 32, also decreased those of 22:6n-3, resulting in a decrease in the sum of these 22:C PUFA.     

Ethanol Inhalation and Dietary N-6, N-3, and N-9 Fatty Acids in the Rat: Effect on Platelet and Aortic Fatty Acid Composition

The effects of 18-carbon n-6, n-3, and n-9 fatty acid diets and ethanol exposure on the fatty acyl composition of platelets and vascular tissue were examined. An experimental design was devised to control the dietary content of 18-carbon fatty acids. The levels of 18:3n6, 18:3n3 and 18:1n9 were varied by a formulation of dietary oils which contained similar proportions of 18:2n6. Male Sprague-Dawley rats were fed a purified diet containing 11% by weight of either borage oil (BOR) rich in 18:3n6, linseed/safflower oil (LSO) rich in 18:3n3, or sesame oil (SES) rich in 18:1n9 for 7 weeks and exposed to ethanol vapors by means of inhalation for the final 6 days of the dietary regimen. Moderate blood ethanol levels of 118 +/- 6.6 mg/dl were obtained. Total lipids were extracted from platelets and aortae, and the fatty acid distributions were analyzed by gas chromatography. BOR feeding resulted in increases in the proportion of n-6 fatty acids (18:3n6, 20:3n6, 20:4n6) in platelets and aorta. Animals fed the LSO diet had increased levels of n-3 fatty acids (18:3n3, 20:5n3, 22:6n3). The SES-based diet resulted in an increase in 18:1n9 in both aorta and platelets. Following ethanol exposure alone, the most marked change in the fatty acid profile was a decrease in 20:4n6 in the platelet. This effect was not observed in rats supplemented with BOR. No significant changes were observed in the aortic fatty acid content at this level of ethanol exposure. The results suggested that, in the rat, a diet enriched with BOR effectively prevented ethanol-induced alterations in platelet fatty acid composition.     

Chronic Ethanol Consumption Alters Effects of Ethanol In Vitro on Brain Membrane Structure of High Alcohol Sensitivity and Low Alcohol Sensitivity Rats

In this study, we examined if differences in initial membrane sensitivity to ethanol were associated with development of membrane tolerance to ethanol. High Alcohol Sensitivity (HAS) and Low Alcohol Sensitivity (US) rats were administered a 15% ethanol solution in water as the sole source of fluid for 30 days. The amount of ethanol consumed per day did not significantly differ between the HAS and LAS rats. Development of membrane tolerance to in vitro effects of ethanol has been previously reported for bulk membrane fluidity and protein-lipid interaction. Our data expands the understanding of "membrane tolerance" phenomenon to protein distribution and bi-layer interdigitation. We also introduce genotype-dependent and genotype-independent properties of the membrane tolerance to ethanol. Chronic ethanol treatment produced genotype-dependent and genotype-independent membrane tolerance to ethanol. The in vitro effects of ethanol on synaptic plasma membrane (SPM) protein distribution and lipid bilayer interdigitation were abolished or decreased in the SPM of chronic ethanol-treated HAS rats, as compared with the SPM of HAS control rats (genotype-dependent tolerance). Protein distribution and bilayer interdigitation were not affected by ethanol in vitro in either chronic ethanol-treated or control LAS rats. Genotype-independent tolerance to ethanol in vitro was observed for SPM annular and bulk bilayer fluidity in chronic ethanol-treated HAS and LAS rats. It is concluded that initial sensitivity to ethanol contributes to the development of membrane tolerance to ethanol in HAS and LAS rats.     

Dietary fatty acid supplementation alters stress reactivity and performance in man

Certain dietary polyunsaturated fatty acids, gamma linolenic (18:3n-6) and eicosapentaenoic (20:5n-3) acid, attenuate cardiovascular reactivity to stress in rats. To study their effects on cardiovascular reactivity to acute stress in man, 30 men were randomly assigned to one of three groups and given 28 day supplements of borage oil (containing 18:3n-6), fish oil (containing 20:5n-3), or olive oil (placebo). Reactivity to the Stroop colour-word conflict test was assessed prior to and following treatment. Borage oil alone attenuated blood pressure and heart rate responses to stress, increased skin temperature, and improved task performance. These data suggest that diet may be used to alter stress reactivity in man.     

Ethanol-induced changes in lipid composition of intestinal microvillus membrane in rats fed different dietary fats

BACKGROUND/METHOD: The effect of feeding ethanol for 5 weeks on the lipid composition of the intestinal microvillus membrane (MVM) was studied in rats fed a commercial rat pellet (RP) diet or purified diets containing 10% coconut oil (CCO), corn oil (CO) or fish oil (FO). RESULTS: A low cholesterol/phospholipid ratio and increased saturated fatty acid level were observed in MVM from the CCO or FO groups. Chronic administration of ethanol to RP- or CO-fed animals increased phospholipids, total and free cholesterol, and the triglyceride and ganglioside content of MVM. The free cholesterol and phospholipid content was reduced while the triglyceride level remained unaffected by ethanol treatment in the CCO or FO groups. Ethanol ingestion decreased 10:2 and 20:4 (n-6 fatty acids) but increased the saturated fatty acid content of MVM in all the dietary groups except in CCO-fed animals where the 18:2 level was not affected. An elevated 18:1, but decreased 22:6 percentage was observed in the ethanol-fed FO group. The fatty acid composition of MVM from the CCO-fed group was least affected by ethanol treatment. CONCLUSION: These observations suggest that the type of dietary fat modifies ethanol-mediated alterations in MVM lipid composition.     

The effects of N-6 polyunsaturated fatty acid supplementation on the lipid composition and atherogenesis in mouse models of atherosclerosis

Despite numerous studies, the precise role of dietary n-6 polyunsaturated fatty acids in the pathogenesis of atherosclerosis remains controversial. It has been shown that feeding an n-6-enriched diet resulted in decreased atherosclerosis in African green monkeys and was associated with a reduction in LDL levels. However, other authors reported that n-6 supplementation increased the oxidative stress and the susceptibility of LDL to undergo in vitro oxidation, thus potentially enhancing atherosclerosis. The present study was designed to investigate the effect of dietary supplementation of n-6 polyunsaturated fats (safflower oil), as compared with a saturated fat-rich diet (Paigen), on the blood lipid profile and atherosclerosis in two mouse models. In the first experiment, female C57BL/6 mice (n=23–30 per group) were fed a cholate containing Paigen diet, a safflower oil-rich diet (with cholate), or normal chow for 15 weeks. No significant differences between the high fat diet groups were evident with respect to total cholesterol, LDL, HDL or triglyceride levels. The extent of aortic sinus fatty streaks did not differ significantly between the two groups. In the second experiment, LDL-receptor-deficient (LDL-RD) mice (n=20–30 per group) were randomized into similar dietary regimens. Mice consuming a safflower oil-enriched diet developed significantly less atherosclerosis, in comparison with Paigen diet-fed mice. A reduction in LDL levels, although not of a similar magnitude as the reduction in atherosclerosis, was evident in the safflower oil-fed mice when compared to the Paigen diet-fed littermates. In both mouse models of atherosclerosis, LDL isolated from the plasma of mice on the n-6 polyunsaturated diet was rendered slightly more susceptible to oxidation in vitro, as indicated by a shorter lag period for diene formation. Thus, the effects of n-6 fatty acids on the lipoprotein composition and other potential influences may have contributed to the anti-atherogenic effect in the LDL-RD mouse model.     

Fluidity and Lipid Composition of Mouse Biomembranes during Adaptation to Ethanol

Showing that ethanol added in vitro increased the fluidity of mouse erythrocyte and synaptosomal membranes and that the same membranes isolated from mice after chronic treatment with ethanol had increased cholesterol and were resistant to ethanol in vitro, the study suggests that the animals had adapted to the chronic presence of the drug by changing their membrane lipid composition to offset the fluidizing effects of ethanol.