Reduction in plasma cholesterol and increase in biliary cholesterol by a diet rich in n-3 fatty acids in the rat

Cholesterol and lipoprotein metabolism were investigated in a group of rats fed a fish oil-supplemented diet, a rich source of n-3 fatty acids. For comparison purposes, other groups of rats were fed either safflower oil (n-6 fatty acids) or coconut oil (saturated fatty acids). Diets were isocaloric and contained identical amounts of cholesterol. Rats fed fish oils for 2 weeks showed a 35% lower plasma cholesterol level than rats fed safflower oil, who in turn showed a 14% lower plasma cholesterol level than those fed coconut oil. The fall in plasma cholesterol level with fish oils was associated with significant falls in low density and high density lipoprotein cholesterol levels, but with no significant change in the ratio of low density to high density lipoprotein cholesterol. The fatty acid compositions of plasma, hepatic, and biliary lipids showed relative enrichment with n-3 fatty acids, reflecting the composition of the diet. The fish oil diet increased the basal secretion rate of cholesterol into bile, but the bile acid secretion rate remained unchanged. It is suggested that n-3 fatty acids reduce the plasma cholesterol level in rats by increasing the transfer of cholesterol into bile.     

Age-associated changes in rat plasma lipids, platelet fatty acids and prostacyclin release

The effect of age on plasma lipids, platelet fatty acids and prostacyclin release was studied in the rat. The contents of arachidonic acid, cholesterol, bile acids and free fatty acids in the plasma of aged rats (15 months old) were higher than those of young rats (3 months old). No significant differences in fatty acid composition of platelet lipids and release of prostacyclin from aortas between young and aged rats were observed. The data suggest that plasma lipids may play a more important role in the development of cardiovascular disease with increasing age than prostaglandins do.     

Effects of ω3 Polyunsaturated Fatty Acids on Growth and Tissue Fatty Acid Compositions of Maternal Rats and Their Progeny

The effects of ω3 polyunsaturated fatty acids [PUFA; mainly eicosapentaenoic acid (20: 5, ω3) and docosahexaenoic acid (22:6, ω3)] on the growth, tissue weights and fatty acid compositions of tissue total lipids in female rats and their progeny were investigated. Female rats of the Wistar strain, weighing 77~94g, were fed a 25% casein diet containing 5% of either corn oil (control), sardine oil or PUFA ethyl ester for 8 ~ 9 weeks prior to mating, and during gestation and lactation, and then for a further 2 weeks. The progeny were weaned to the maternal diet and then the latter was administered for a further 2 weeks. Dietary changes in the body weights of the dams were not generally seen, but the body weights at birth and growth of the offspring from the females supplied with the PUFA diet were inferior compared to those of the other groups. The fertility did not differ among the dietary groups. The weights of several tissues in the dams and the progeny increased in proportion to their body weights but not that of the progeny brain, which remained ' almost unchanged by the dietary fats. As to the fatty acid compositions of total lipids in the tissues, on the whole, decreased levels of ωβ fatty acids and increased percentages of ω3 fatty acids were found in the sardine and PUFA groups, the changes being greater in the PUFA group than in the sardine one. Such findings due to the feeding of PUFA were more remarkable in the progeny compared with in the dams. Eicosatrienoic acid (20: 3, ω9) was almost completely undetectable in the tissue total lipids of all the dietary groups.     

Soybean Oil Supplementation Improves Growth and Prevents Docosapentaenoic Acid (22: 5n–6) Accumulation in Tissues of Rats Fed on Palm Oil Diet

Effects of soybean oil supplementation as a source of linoleic and α-linolenic acids in a palm oil diet on growth and docosapentaenoic acid (22: 5n–6) levels in tissue lipids in male Sprague–Dawley rats were studied. The rats fed for two months with the diets containing soybean oil (10–50%) in palm oil showed significantly higher weight gain than that in rats fed a diet containing only palm oil as a fat source. The highest weight gain was observed in rats fed 50% soybean oil blended in palm oil. Such performance was also better than those observed in rats received diets containing soybean oil alone or canola oil alone. Addition of soybean oil to the palm oil diet prevented 22: 5n–6 accumulation in plasma, red blood cells, liver, heart, and retinal lipids with a compensative increase of docosahexaenoic acid (22:6n–3). Poly-unsaturated fatty acid profiles of brain were not affected by the addition of soybean oil. Changes in arachidonic acid contents in organs were not observed. The results indicated that soybean oil supplementation increases the weight gain and prevents the accumulation of 22: 5n–6 in the tissues which were observed in the rats fed a diet containing palm oil alone.     

Comparative hypocholesterolemic effects of five animal oils in cholesterol-fed rats

The hypocholesterolemic efficacy of various animal oils was compared in rats given a cholesterol-enriched diet. After acclimatization for one week, male F344 DuCrj rats (8 weeks of age) that had been fed with a conventional diet were assigned to diets containing 5% of oil from emu (Dromaius), Japanese Sika deer (Cervus nippon yesoensis, Heude), sardine, beef tallow, or lard with 0.5% cholesterol for 6 weeks. After this feeding period, the concentrations of serum total cholesterol and of very-low-density lipoprotein + intermediate-density lipoprotein + low-density lipoprotein-cholesterol in the sardine oil group were significantly lower than those in the other groups. The serum high-density lipoprotein-cholesterol concentration in the Japanese Sika deer oil group was significantly higher than that in the other groups. The atherosclerotic index and liver cholesterol concentration in the sardine oil and Japanese Sika deer oil groups were significantly lower than those in the other groups. The fecal cholesterol excretion by the Japanese Sika deer oil group was significantly higher than that of the other groups, except for the sardine oil group, and the fecal bile acid excretion by the sardine oil group was significantly higher than that of the other groups, except for the lard group. These results suggest that Japanese Sika deer oil reduced the atherosclerotic index and liver cholesterol concentration in the presence of excess cholesterol in the diet as well as sardine oil did by increasing the excretion of cholesterol from the intestines of rats.     

Liver Lipid Composition and Antioxidant Enzyme Activities of Spontaneously Hypertensive Rats After Ingestion of Dietary Fats (Fish, Olive and High-Oleic Sunflower Oils)

Hypertension is associated with greater than normal lipoperoxidation and an imbalance in antioxidant status, suggesting that oxidative stress is important in the pathogenesis of this disease. Although many studies have examined the effect of antioxidants in the diet on hypertensión and other disorders, less attention has been given to the evaluation of the role of specific dietary lipids in modulating endogenous antioxidant enzyme status. Previously, we have described that liver antioxidant enzyme activities may be modulated by consumption of different oils in normotensive rats. The purpose of the present study was to examine the effects of feeding different lipidic diets (olive oil, OO, high-oleic-acid sunflower oil, HOSO, and fish oil, FO) on liver antioxidant enzyme activities of spontaneously hypertensive rats (SHR). Plasma and liver lipid composition was also studied. Total triacylglycerol concentration increases in plasma and liver of animals fed on the HOSO and OO diets and decreases in those fed on the FO diet, relative to rats fed the control diet. The animals fed on the oil-enriched diet show similar hepatic cholesterol and phospholipid contents, which are higher than the control group. Consumption of the FO diet results in a decrease in the total cholesterol and phospholipid concentration in plasma, compared with the high-oleic-acid diets. In liver, the FO group show higher levels of polyunsaturated fatty acids (PUFA) of the (n-3) series, in relation to the animals fed on the diets enriched in oleic acid. Livers of FO-fed rats, compared with those of OO- and HOSO-fed rats showed: (i) significantly higher activities of catalase, glutathione peroxidase and Cu/Zn superoxide dismutase; (ii) no differences in the NADPH-cytochrome c reductase activity. The HOSO diet had a similar effect on liver antioxidant enzyme activities as the OO diet. In conclusion, it appears that changes in the liver fatty acid composition due mainly to n-3 lipids may enhance the efficiency of the antioxidant defence system and may yield a benefit in the hypertension status. The two monounsaturated fatty acids oils studied (OO and HOSO), with the same high content of oleic acid, but different content of natural antioxidants, had similar effects on the antioxidant enzyme activities studied.     

Dietary fatty acids and oxidative stress in the heart mitochondria

Our study compared the effects of different oils on oxidative stress in rat heart mitochondria, as well as on plasma parameters used as risk factors for cardiovascular disease. The rats were fed for 16 weeks with coconut, olive, or fish oil diet (saturated, monounsaturated, or polyunsaturated fatty acids, respectively). The cardiac mitochondria from rats fed with coconut oil showed the lowest concentration of oxidized proteins and peroxidized lipids. The fish oil diet leads to the highest oxidative stress in cardiac mitochondria, an effect that could be partly prevented by the antioxidant probucol. Total and LDL cholesterols decreased in plasma of rats fed fish oil, compared to olive and coconut oils fed rats. A diet enriched in saturated fatty acids offers strong advantages for the protection against oxidative stress in heart mitochondria.     

Effects of structured lipids containing eicosapentaenoic or docosahexaenoic acid and caprylic acid on serum and liver lipid profiles in rats

The physiological activity and effect on lipid metabolism of four types of structured lipids (SLs), that contain caprylic acid (C8) and either eicosapentaenoic (EPA) or docosahesaenoic acid (DHA), were evaluated in male Wistar rats fed experimental diets containing 7% (wt %) of each SL and 3% (wt %) soybean oil for 28 days. Control rats were fed a diet containing 10% (wt %) soybean oil. The relative perirenal adipose tissue weights of rats fed D-8-8 and 8-D-8 diets were significantly lower than those of other groups. We observed significantly lower serum cholesterol concentrations in rats fed SLs than those of control group over experimental period. The serum lipids concentrations in rats fed diets containing SLs were significantly lower P < 0.05) than those of soybean oil group. The fatty acid compositions of WAT did not reflect the structural differences in the triglyceride. These results suggest that the physiological effects of the SLs used in this study were due to the fatty acids rather than the structural specificity. Therefore, further study will be needed to ascertain the most desirable structural configuration.     

Changes of Linoleic,Arachidonic and Eicosapentaenoic Acids in Rat Platelet,Aorta and Plasma Lipids after Changing from a Sardine Oil Diet to a Corn Oil Diet

When rats were fed on a diet containing sardine oil (SO) for 10 days, 20:5 (eicosapentaenoic acid) was incorporated into the platelet, aorta and plasma lipids. The 20:5/20:4 (arachidonic acid) ratios of phospholipids were higher in platelets than in aortas. When the diet was changed from SO to corn oil (CO), the levels of 20:5 in the plasma lipids and platelet phospholipids decreased with an increase of 20:4. Although the 20:5 levels of phospholipids in the aortas decreased, 20:4 did not increase during feeding with the CO diet for 4 days. The 20:5/20:4 ratios of the phosphatidylcholine in platelets and aortas rapidly changed from 5.0 and 1.1 to 2.4 and 0.6, respectively. The linoleic acid level of phosphatidylcholine in platelets and aortas increased rapidly by changing from the SO diet to the CO diet, but this fatty acid was not incorporated into phosphatidylinositol of the platelets and aortas.     

Blood cholesterol and hepatic bile secreting function in rats of different ages under normal conditions and after maintenance of an atherogenic diet

The quantity of bile secreted during 24 hours and the concentration of total bile acids in adult 11--12-months-old and aged 27--29-month-old rats were determined by cannulation of common bile duct. As revealed, the difference in bile acid production and in the concentrations of cholesterol fractions in the liver and plasma between the adult and aged rats on a standard diet was insignificant. But the excretion of bile acids was markedly elevated both in adult and aged rats on atherogenous diet. The level of total and ester cholesterol in the plasma was higher in aged rats than in adult animals.     

Effect of dietary oils on lipid peroxidation and on antioxidant parameters of rat plasma and lipoprotein fractions.

In order to investigate the influence of fatty acid pattern and antioxidants other than vitamin E on lipid peroxidation and antioxidant levels of plasma very low density and low density lipoproteins (VLDL + LDL), the effects of three diets (equalized for vitamin E) containing soybean oil, olive oil, or an oleate-rich mixture of triglycerides (triolein) were studied in rats. A significantly lower concentration of thiobarbituric acid-reactive substances (TBA-RS) in plasma and lipoproteins was found after the olive oil diet (soybean oil, 3.7 +/- 0.4 nmol/ml; triolein, 2.1 +/- 0.5 nmol/ml; olive oil, 1.5 +/- 0.3 nmol/ml, in plasma) (soybean oil, 0.99 +/- 0.16 nmol/ml; triolein, 0.96 +/- 0.13 nmol/ml; olive oil, 0.38 +/- 0.12 nmol/ml, in the VLDL + LDL fraction). Furthermore, the results from in vitro copper-induced lipid peroxidation, expressed in terms of conjugated dienes, lipid hydroperoxides, and TBA-RS content, showed that VLDL + LDL particles from olive olive oil-fed rats were remarkably resistant to oxidative modification. The results suggest that the fatty acid unsaturation of dietary oils is not the only determining factor of the antioxidant capacity of lipoproteins in this animal model. The maximal protection observed after the olive oil diet may be explained by the presence of other unidentified antioxidants in addition to vitamin E, derived from oil intake. Therefore, the optimal balance between the content of unsaturated fatty acids and natural antioxidants in dietary oils appears to be of major importance.     

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.     

Intestinal absorption of fish oil in rats previously adapted to diets containing fish oil or corn oil.

A study was conducted to evaluate whether the composition of previous dietary fat affects the absorption and composition of lymph obtained after a meal of fish oil. Adult male Sprague-Dawley rats were fed diets containing either corn oil or fish oil (MaxEPA) for 2 weeks. They were then given intraduodenally a bolus of an emulsion of 0.5 ml of fish oil plus 0.5 ml of 20 mM sodium taurocholate. Intestinal lymph was collected from a cannula in the main intestinal lymph trunk for various times after oil administration. Rats proportion of the test dose fo fish oil than those fed corn oil. There was an effect of previous diet on the fatty acid composition of the lymph. Rats fed fish oil had a higher percentage of eicosapentaenoic and docosahexaenoic acids in the lymph lipids than those fed corn oil while those fed corn oil had a higher percentage of linoleic acid. These results rule out decreased intestinal absorption as a mechanism for the hypotriacylglycerolemic effect of dietary fish oils. They also indicate a significant contribution of endogenous lipids to the fatty acids in lymph.     

Isolation of a yeast growing on sardine oil and its characteristics

A yeast strain, FO-144Cl, was isolated from a soil sample, using crude sardine oil, which contains a large quantity of poly-unsaturated long-chain fatty acids, as a sole carbon source. This strain was identified as a species of Candida. A medium for its growth was optimized by statistical methods and optimal temperature for the growth was from 28 to 30°C. Among the natural oils and fats tested, the yeast grew best on olive oil and grew better on the crude sardine oil than on a refined one. The yield of dry cells was 17.6 mg/ml after 24 h, using 2% crude sardine oil. The maximum growth rate was 0.36, 0.25, and 0.21 h⁻¹ with crude sardine oil, soybean oil, and olive oil, respectively. The content of crude fat in the yeast cells was 15.1% and half of the total cell lipid was triglyceride. Fatty acid compositions of the lipid and oily fractions left in the medium after cultivation were analyzed. Little unsaturated long-chain fatty acids (>C₁₈) was observed in the cell lipids, but they were left concentrated in the medium.     

Effect of dietary fats on arachidonic acid and eicosapentaenoic acid biosynthesis and conversion to C22 fatty acids in isolated rat liver cells

The desaturation, chain elongation and esterification of [1-14C]eicosapentaenoic acid, [1-14C]arachidonic acid, [1-14C]eicosatrienoic acid, [1-14C]linolenic acid and [1-14C]linoleic acid were studied in isolated liver cells. Rats fed diets with either 15% hydrogenated coconut oil or 15% partially hydrogenated marine oil, both deficient in essential fatty acids, 15% soybean oil or standard pellet diet with 6% fat, were used. The delta 4-desaturation of 22:5(n - 3) and 22:4(n - 6) as well as the delta 6-desaturase activity was distinctly higher in cells from animals fed coconut or marine oil than with soybean oil or standard pellet. The rate of delta 5-desaturation of 20:3(n - 6) and 20:4(n - 3) was nearly the same in cells from rats fed coconut, marine and soybean oils and higher than with standard pellet. The chain elongation of 20:5(n - 3) to 22:5(n - 3) was distinctly more pronounced than the elongation of 20:4(n - 6) with all four diets. 20:5(n - 3) was mainly esterified in the phospholipids with marine and coconut oils, and mainly in triacylglycerol with standard pellet and soybean oils. The proportion of [1-14C]20:4(n - 6) in the phospholipids to that in triacylglycerol decreased in the order marine oil greater than coconut oil greater than standard pellet greater than soybean oil. The different endogenous arachidonic acid content in the phospholipids induced by the different diets increased in the same order. 20:5(n - 3) was rapidly esterified in triacylglycerol and phospholipids, then liberated especially from the triacylglycerol fraction, chain elongated to 22:5(n - 3) and reesterified.     

Reversibility of the effects of dietary fish oil on the fatty acid composition of the brain and retina of growing chicks.

Dietary fish oil increases levels of (n-3) fatty acids in the brain and retina of younger animals but has less effect in adults. The duration of the effects of fish oil in young animals, as well as the extent of reversibility of the effects, are unknown. Laying hens were fed either a fish oil diet or a soybean oil-based control diet. Resulting chicks were assigned to three diet groups: chicks from fish oil and soybean oil hens were continued on fish oil and soybean oil diets, respectively, for 0, 3, 6, or 9 weeks, and additional chicks from the fish oil hens were fed the fish oil diet for 0, 3, or 6 weeks and then reversed to the soybean oil diet for a period of 3 weeks. The fatty acid composition of the brain, retina, liver, and serum of the reversal chicks was compared with chicks fed the fish oil diet only or the soybean oil diet only. Brain levels of docosahexaenoic acid (22:6(n-3)) decreased substantially when reversal from the fish oil diet to the control diet was begun at hatching, but did not decrease when reversal was begun at later times. Other (n-3) fatty acids in the brain, docosapentaenoic acid (22:5(n-3)) and eicosapentaenoic acid (20:5(n-3)), decreased substantially at all ages, and to a greater extent than 22:6(n-3). Brain arachidonic acid (20:4(n-6)), which was low in fish oil chicks, rose to control after reversal at hatching, but recovered only partially when reversal was begun at later times. A similar patterns was observed in the retina. Serum and liver (n-3) fatty acids fell to control in all reversal chicks, and (n-6) fatty acids increased to control, except in chicks reversed at 6 weeks. This study demonstrates that by 3 weeks of age the chick brain strongly resists diet-induced lowering of high levels of 22:6(n-3).     

Malondialdehyde production and erythrocyte membrane resistance to free radicals, in function of adequate or inadequate protein intake, associated with different oils (sunflower, soybean, coconut, salmon)]

Requirements in polyunsaturated fatty acids (PUFA) of series n-3 and n-6 may be amplified and their metabolism, transport, and utilization may be impaired in the long term, by protein depletion. The aim of this study was to evaluate, in young rats, malondialdehyde (MDA) production and erythrocyte membrane antioxidative defense, when they were fed balanced (20% casein) or depleted (2% casein) protein diet associated with various oils (sunflower, soybean, coconut or salmon). Over a short period (28 days), eight groups of 10 male Wistar rats were fed eight different diets: TOC (20% casein + 5% sunflower oil), TOd (2% casein + 5% soybean oil), SOC (20% casein + 5% soybean oil), SOd (2% casein + 5% soybean oil), COC (20% casein + 5% coconut oil), COd (2% casein + 5% coconut oil), SAC (20% casein + 5% salmon oil), SAd (2% casein + 5% salmon oil). Blood was removed, MDA was assessed in plasma (reaction with thiobarbituric acid). Washed erythrocytes were subjected to organic free radical generator (Kit KGRL 400 Spiral R.D., Couternon, 21560 France). The haemoglobin released was analysed by spectrophotometry. The total anti-radical defense status was expressed as the length of time to reach 50% hemolysis (T 50% in min). Plasma of deficient groups (2% casein) exhibited low concentrations of protein, particularly with coconut and salmon oils; phospholipid and total cholesterol, excepted with diet containing coconut oil; triacylglycerol; and VLDL. Malondialdehyde. In groups fed balanced protein diets, the lowest values were obtained with salmon and coconut oils. MDA contents of groups TOd, COd and SAd were higher than those of their respective control groups, but significantly only in group COd. Antiradical defense status. Total anti-radical defence status in erythrocytes was not modified in the short term by balanced or depleted protein diets which ever oil was used, despite deep changes in fatty acid composition of membrane phospholipids. In particular, phospholipid contents in eicosapentaenoic, docosahexaenoic acids were greatly enhanced by the consumption of salmon oil compared to the values obtained with coconut oil.     

4 种不同脂肪源对太平洋鲑生长和体组成的影响

在日粮中添加11.5%的4 种不同来源脂肪饲养180 尾初始重约为110g 的太平洋鲑(Oncorhynchus spp.)于水泥池中56d。实验分4 组,每组3个平行池,每池15尾鱼。研究日粮中4 种不同来源脂肪对淡水养殖太平洋鲑生长性能、体组成与品质的影响。4 组脂肪源分别为鱼油(实验1 组)、大豆油(实验2 组)、大豆磷脂(实验3 组)和玉米油(实验4 组)。实验表明:(1) 实验各组太平洋鲑存活率相似,但大豆磷脂组的特定生长率显著好于鱼油组、大豆油组和玉米油组(P0.05)。大豆磷脂组、大豆油组和玉米油组的饲料效益显著好于鱼油组(P< 0.05); (2) 大豆油组、大豆磷脂组和玉米油组太平洋鲑肠系膜脂肪与肝脏脂肪含量不同程度低于鱼油组,而肌肉中脂肪含量不同程度低于鱼油组; (3) 实验各组太平洋鲑肝脏脂肪、肌肉脂肪和肠脂中总多不饱和脂肪酸组成基本相似,但玉米油组、大豆磷脂组和大豆油组太平洋鲑总n-3 多不饱和脂肪酸比例较鱼油组显著下降,而总n-6 系多不饱和脂肪酸比例显著提高(P<0.05);(4) 玉米油组、大豆磷脂组和大豆油组太平洋鲑血浆中脂肪分解酶、甘油三酯和高密度脂蛋白指标较鱼油组不同程度上升;(5) 实验各组太平洋鲑解剖组织学检查未见异常病理变化。实验结果表明,淡水养殖条件下,太平洋鲑日粮中脂肪以添加大豆磷脂的生长性能最好,大豆油、玉米油和鱼油效果相似,添加玉米油、大豆磷脂和大豆油均不影响太平洋鲑健康状况和品质。       

The adaptive effects of dietary fish and safflower oil on lipid and lipoprotein metabolism in perfused rat liver

To elucidate the mechanisms underlying the plasma triacylglycerol-lowering effects of certain fish oils, livers from male rats fed either a standard commercial diet (controls) or diets supplemented with 15% (w/w) fish or safflower oils were perfused with undiluted rat blood. Rates of hepatic lipogenesis, measured by the incorporation of 3H2O into fatty acids, followed the order: control greater than safflower oil greater than fish oil. Secretion of newly synthesized fatty acids in very-low-density lipoproteins was also inhibited by the feeding of both oil-supplemented diets with the greater suppression being seen in livers from animals fed fish oil. The hepatic release of very-low-density lipoprotein triacylglycerol mass was also significantly depressed in animals fed the fish oil-supplemented diet but not in those fed safflower oil. Ketogenesis did not differ between livers from rats fed the control and safflower oil diets but was significantly raised in the fish oil group. Increased ketogenesis with fish oil was paralleled by a decrease in the sensitivity of carnitine palmitoyl transferase of isolated mitochondria to inhibition by malonyl-CoA. The inhibitory effect of malonyl-CoA in the safflower oil group was intermediate between that in the fish oil and control groups. Activities of glycerophosphate acyltransferase with either palmitoyl-CoA or oleyl-CoA were increased by feeding oil-supplemented diets. Activity with palmitoyl-CoA that was suppressible by N-ethylmaleimide was also considerably diminished in both groups. The results indicate that the lowering of plasma triacylglycerols by fish oil reflects: (a) diminished lipogenesis; (b) increased fatty acid oxidation possibly in peroxisomes; and (c) diminished secretion of triacylglycerols by the liver.     

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.