Hepatic cholesterol and fatty acid synthesis in pregnant and fetal rats: effect of maternal dietary fat and cholestyramine.

Previous studies from this laboratory have demonstrated that 20% rather than 5% (wt/wt) safflower oil or addition of 5% (wt/wt) cholestyramine to the diet of pregnant rats leads to an increase in the activity of 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme of cholesterol synthesis, in the fetal liver. Total cholesterol, however, was not altered in fetal plasma or liver. The effect of these diets on cholesterol and fatty acid synthesis in vivo was therefore studied in fetal and maternal liver. In fetuses of rats fed a reference nonpurified diet, rates of hepatic cholesterol and fatty acid synthesis decreased from gestation d 20 to 21. In contrast, total and active 3-hydroxy-3-methyl-glutaryl CoA reductase activity increased. Adding cholestyramine to the diet or modifying the quantity of safflower oil fed had no effect on fetal hepatic lipogenesis. Maternal hepatic cholesterol synthesis was greater in rats fed cholestyramine, whereas fatty acid synthesis was lower in the dams fed the diet containing 20% compared with 5% safflower oil. The results suggest near-term fetal liver 3-hydroxy-3-methylglutaryl CoA reductase activities do not reflect fetal cholesterol synthesis in vivo.     

Mammary tumor lipids and plasma lipoproteins in DMBA-intubated rats fed olive or safflower oils

The effects of feeding olive and safflower oils on lipid and fatty acid composition of mammary tumors, plasma lipids and lipoproteins, and the nuclear magnetic resonance (NMR) spectra of plasma were investigated in rats. 7-12-Dimethylbenz[a]anthracene (DMBA)- and placebo-intubated male Sprague-Dawley rats were fed 20% fat diets containing 18:2n-6 (wt/wt) from either high-linoleic safflower oil (SL, 14.6% 18:2n-6), high oleic safflower oil (SO, 3.4% 18:2n-6), olive oil (OO, 1.1% 18:2n-6), or olive oil supplemented with 18:2n-6 (OL, 3.4% 18:2n-6) for 16 weeks. Our result indicated that tumor composition of 18:1n-9 and 18:2n-6 reflected the diet, but tumor neutral lipid (NL) was more reflective of diet than was tumor phospholipid (PL). The 20:4n-6 content of tumor PL was constant in all of the dietary groups despite threefold higher levels of 18:2n-6 in tumor PL from animals fed SL than from those fed SO, OO, or OL diets. This suggests a possible feedback inhibition of delta 6-desaturase by the higher content of 18:2n-6 associated with SL feeding No diet effects were obtained for tumor total lipid, NL, PL, cholesterol, and triglyceride contents. Plasma lipoprotein changes were more reflective of diet than tumorigenesis except for apolipoprotein-E, which was lower, and for very low-density lipoprotein cholesterol and low-density lipo protein, which were higher in tumor-bearing rats. Plasma NMR analysis indicated no difference in the average line widths of the methyl and methylene resonances for tumor-bearing and nontumor-bearing rats fed any of the diets.     

Relative effects of dietary oleic- and linoleic-rich oils on plasma lipoprotein composition in rats

Plasma lipoprotein composition and hepatic lipid content were investigated in male Sprague-Dawley rats (104 +/- 2 g) fed diets containing 12% olive oil [OO, 70% 18:1(n-9)], 12% high oleic safflower oil [SO, 70% 18:(ln-9)] or 12% high linoleic safflower oil [SL, 73% 18:2(n-6)] for periods of up to 10 wk. Fasting plasma triglycerides were significantly higher after feeding oleic-rich diets than after feeding SL for 3, 5 and 6 wk. At 6 wk VLDL triglycerides were two- to threefold higher in rats fed OO or SO than in those fed SL, but by 10 wk both plasma and VLDL triglycerides were similar. A greater proportion of HDL2 (diameter 8.0-12.1 nm), a lower proportion of HDL1 (diameter 12.2-17.0 nm) and lower HDL apo E content occurred in rats fed OO and SO than in those fed SL at both 6 and 10 wk. LDL and HDL protein and cholesterol concentrations were not different with feeding SO or SL. After 10 wk of feeding the experimental diets, rats fed OO had significantly lower HDL protein, cholesterol and apo E concentrations and significantly higher hepatic triglyceride content compared to rats fed SO or SL, P less than 0.05. These data suggest that HDL and hepatic lipid content are determined by some property of the dietary oil other than its oleic acid content.     

Effect of dietary safflower phospholipid on plasma and liver lipids in rats fed a hypercholesterolemic diet.

The effect of safflower phospholipid (SP) on plasma and liver lipids in rats fed a hypercholesterolemic diet was examined. Triglyceride mixture (SPO) of safflower oil and palm oil (8:2) containing almost comparable amounts of linoleic acid to safflower phospholipid was used as a control diet. Similarly, the effect of paste safflower phospholipid (PSP) which contains approximately 45% of neutral lipid was also compared to safflower oil (SO). Concentrations of total cholesterol in plasma and liver of rats fed the SP diet were markedly decreased in comparison with those of the other diets, but a slight reduction of total cholesterol in plasma and liver was observed in rats fed PSP diet. SP and PSP induced a reduction in the plasma level of low density lipoprotein (LDL) cholesterol as well as an increase in the level of high density lipoprotein (HDL) cholesterol. The activity of plasma lecithin-cholesterol acyltransferase (LCAT) was greatly increased in rats fed SP diet. These results suggest that the safflower phospholipids suppress the elevation of plasma and liver cholesterol and that this effect may depend on the phospholipid content in dietary lipid.     

The effect of dietary safflower phospholipid and soybean phospholipid on plasma and liver lipids in rats fed a hypercholesterolemic diet.

The effect of dietary safflower phospholipid (Saf-PL) and soybean phospholipid (Soy-PL) on plasma, liver, and fecal lipids in rats fed a hypercholesterolemic diet was compared with that of triglyceride mixture (controls). Triglyceride mixture (SP-Oil) of safflower oil and palm oil (8:2) contained almost comparable amounts of linoleic acid to safflower phospholipid or soybean phospholipid. Concentration of total cholesterol in plasma of rats fed the Saf-PL and Soy-PL diets were significantly decreased in comparison with that of the SP-Oil diet. Similarly, both Saf-PL and Soy-PL induced a reduction in the concentration of liver cholesterol compared with SP-Oil; Saf-PL indicated the lowest value. Saf-PL only significantly increased the level of high density lipoprotein (HDL) cholesterol. The level of chylomicron plus very low density lipoprotein (VLDL) cholesterol was lower in rats fed the Saf-PL and Soy-PL diets than that of the SP-Oil diet. The activity of plasma lecithin-cholesterol acyltransferase (LCAT) was increased in rats fed Saf-PL and Soy-PL. Saf-PL and Soy-PL caused an enhanced excretion of fecal neutral steroids, but not acidic steroids compared with SP-Oil. These results suggest that, in addition to soybean phospholipid, safflower phospholipid suppresses the elevation of plasma and liver cholesterol and that this effect may be brought about by inhibiting the absorption of cholesterol in the small intestine.     

Influence of maternal cholestyramine treatment on cholesterol and bile acid metabolism in adult offspring

To reduce ileal reabsorption of bile acids and to deplete hepatic cholesterol pools, female rats were fed a diet containing 5% (wt/wt) cholestyramine from 4 days prior to mating. Control rats were fed the same diet without cholestyramine. In one group on day 20 of gestation diet-fed dams and their fetuses were investigated. Additional pups were raised in litters of eight and nursed by their mothers for 30 days at which time they were weaned to the control diet. All dams were given the control diet from day 14 of lactation; at no time did neonates have access to cholestyramine. Offspring were raised until 3 months of age then fed the control, cholestyramine or a high fat, high cholesterol diet for 5 days. Maternal cholestyramine produced significant elevation of fetal hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase; fetal 7 alpha-hydroxylase (7 alpha-OH) activity, plasma cholesterol and triglyceride levels, however, were not significantly altered. The elevated HMG-CoA reductase activity persisted in liver and in addition was present in jejunum of 3-month-old male offspring challenged with the control or cholestyramine diet for 5 days. When challenged with the high fat, high cholesterol diet, male offspring from cholestyramine-treated dams had significantly higher plasma cholesterol levels but HMG-CoA reductase and 7 alpha-OH activity similar to controls. Maternal treatment had no apparent effect on plasma triglyceride or hepatic 7 alpha-OH in 3-month-old male offspring.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dietary fatty acid composition in pregnancy alters neurite membrane fatty acids and dopamine in newborn rat brain

The importance of maternal dietary fatty acids on arachidonic acid [AA; 20:4(n-6)] and docosahexaenoic acid [DHA; 22:6(n-3)] in fetal brain nerve growth cone membranes and monoaminergic neurotransmitters was investigated. Rats were fed purified diets containing 20 g/100 g safflower oil with 74.3% 18:2(n-6), 0.2% 18:3(n-3), soybean oil with 55.4% 18:2(n-6), 7.7% 18:3(n-3) or high fish oil with 24.6% 22:6(n-3) through gestation. Tissue for rats within a litter were pooled at birth, brain growth cone membranes prepared and phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylinositol (PI) fatty acids quantified by gas-liquid chromatography. Dopamine, serotonin, and the metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 5-hydroxyindolacetic acid were quantified by HPLC. Growth cone membranes from offspring of rats fed safflower oil had significantly lower, and offspring of rats fed high 22:6(n-3) fish oil had significantly higher 22:6(n-3) in PE, PS and PI than the soybean oil group. The growth cone membrane PC, PE and PS 20:4(n-6) was significantly lower in the fish oil than in the soybean or safflower oil groups. Serotonin concentration was significantly higher in brain of offspring in the safflower oil compared with the soybean oil group. The newborn brain dopamine was inversely related to PE DHA and PS DHA (P < 0.001), but positively related to PC AA (P < 0.05). These studies show that maternal dietary fatty acids may alter fetal brain growth cone (n-6) and (n-3) fatty acids, and neurotransmitters involved in neurite extension, target finding and synaptogenesis. The functional importance, however, is not known at this time.     

Effect of dietary salmon oil feeding on rat heart lipid status

For 2 mo rats were fed a salmon oil diet (12.5%, wt/wt) supplemented with 4.5% (wt/wt) corn oil, a corn oil diet (17%, wt/wt) or a low fat diet (4.4%, wt/wt). Cardiac lipids were analyzed and fatty acid composition of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was determined. Ventricular biopsies were taken for ultramicroscopic examination. Serum cholesterol, triglyceride, phospholipid and vitamin E concentrations were significantly lower in rats fed salmon oil than in those fed the other two diets, whereas serum transaminases and vitamin A were not significantly affected. Cardiac protein, phospholipid, triglyceride and cholesterol concentrations were unaffected by diet. Cardiac phospholipid composition remained unchanged and no significant changes in lyso-PC or lyso-PE levels were observed. However, the salmon oil diet produced a markedly lower n-6/n-3 ratio in both PE and PC than in the other two diets. This was the result of replacement of n-6 polyunsaturated fatty acids (PUFA), primarily 20:4n-6 with n-3 PUFA, primarily 22:6n-3. The unsaturation index of PC and PE was higher with the salmon oil diet than with the other two diets. Ventricular biopsies of rats fed salmon oil showed mild lipid accumulation associated with some lipofuscin-like material. It is suggested that, in rat heart, fish oil led to a moderate accumulation of lipids, the composition of which may include long-chain monounsaturated fatty acids and a degradative form of peroxidized lipids.     

Dietary olive and safflower oils in promotion of DMBA-induced mammary tumorigenesis in rats

Interpretation of studies comparing the efficacy of different dietary fat sources in promoting 7,12-dimethylbenz[a]-anthracene (DMBA)-induced rat mammary tumorigenesis often ignores the fact that about 4% (wt/wt) linoleic acid (18:2n-6) is required for optimal tumor promotion. We therefore fed DMBA-intubated or placebo-intubated female, Sprague-Dawley rats 20% fat diets containing 18:2n-6 (wt/wt) from either high-linoleic safflower oil (SL, 14.6% 18:2n-6), high-oleic safflower oil (SO, 3.4% 18:2n-6), olive oil (OO, 1.1% 18:2n-6), or OO supplemented with 18:2n-6 (OL, 3.4% 18:2n-6) for 16 weeks. Results indicated that OO-fed rats had longer tumor-free time, fewer tumors per rat, and lower tumor incidence compared with SO and OL. Addition of 2.3% 18:2n-6 to OO enhanced tumor promotion (p less than 0.04); SL, SO, and OL demonstrated similar tumor-enhancement effect. About 74% of observed mammary tumors were adenocarcinomas; a greater number of tumors appeared in the thoracic and inguinal than in the cervical and abdominal regions irrespective of diet. These results indicate that once an optimal amount of linoleic acid is provided in the diet, oleic- or linoleic-rich oils have similar effects on promotion of mammary tumors in the rat.     

Differential effects of fish oil, safflower oil and palm oil on fatty acid oxidation and glycerolipid synthesis in rat liver.

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

The effect of dietary fat saturation on plasma and hepatic lipoproteins in the rat

Semipurified diets containing 10% kilocalories from either safflower oil (SO), corn oil (CO), olive oil (OO) or palm oil (PO) were fed to weanling male rats for 2 weeks. The effects of dietary fat saturation on plasma lipids and lipoproteins were: 1) Nonfasted plasma cholesterol concentration was higher in rats fed OO (mean +/- SEM = 81.0 +/- 2.9 mg/dl) vs. CO (67.5 +/- 2.9); 2) plasma chylomicron cholesterol concentration was higher in rats fed OO vs. SO and CO, with PO values in between; and 3) the cholesterol concentration of plasma very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) did not differ among groups. The effects of dietary fat saturation on hepatic lipoproteins (determined by liver perfusion techniques) were: 1) hepatic higher density lipoprotein (d = 1.006-1.21 g/ml) cholesterol production was greater in rats fed SO and CO vs. PO [19.1 +/- 1.2, 17.2 +/- 0.8 and 13.7 +/- 1.6 micrograms/(g liver X 1.5 hour), respectively]; 2) there was no difference in hepatic VLDL cholesterol production among groups; and 3) the ratio of cholesterol to protein of hepatic VLDL and the higher density lipoprotein fraction was higher in rats fed diets rich in polyunsaturated fatty acids versus saturated fatty acids. Dietary fat saturation had no effect on carcass and liver cholesterol concentrations. Since differences in hepatic lipoprotein production were not reflected in plasma lipoprotein patterns, these results suggest that extrahepatic lipoprotein metabolism differs in rats fed diets containing fatty acids of varying saturation.     

Lipid metabolism responses in rats fed beef tallow, native or randomized fish oil and native or randomized peanut oil

In experiments with male Wistar rats, we measured the effects of nonpurified diets containing 9.1% added fat (beef tallow, native or randomized fish oil, native or randomized peanut oil) on apparent digestibility of total fat and individual fatty acids. We also investigated the effects of the diets on plasma contents of triglyceride, cholesterolesters and free and total cholesterol as well as on the fatty acid profiles of plasma and liver phospholipids. Randomization of fish oil or peanut oil had no significant effect on any of the lipid measurements. Fat digestibility was significantly lower in the rats fed beef tallow. Apparent absorption of 18:1(n-9) and polyunsaturated fatty acids was not dependent on the fatty acid profile of the dietary fat. Apparent absorption of 16:1(n-7) and saturated fatty acids was generally highest in the rats fed fish oil. Intake of fish oil or peanut oil significantly decreased plasma triglyceride content. Intake of fish oil resulted in substantially decreased contents of total cholesterol and cholesterolesters in plasma, but intake of peanut oil did not. Efficiency of conversion of 18:2(n-6) into 20:4(n-6) was inhibited by long-chain (n-3) fatty acids.     

Interrelationship of plasma triglycerides and HDL size and composition in rats fed different dietary saturated fats

We investigated the relative effects of different dietary saturated fats on the size distribution, apolipoprotein (apo) and chemical composition of HDL in fasted rats. Male Sprague-Dawley rats (174 +/- 2 g) were fed diets containing 0.035% cholesterol and 16% fat (wt/wt) from corn oil (CO diet) or from 2% CO plus 14% butterfat (BF diet), beef tallow (BT diet), palm oil (PO diet) or coconut oil (CN diet) for 6 wk. Apparent lipid digestibility was significantly lower with the PO and BT diets vs. the CO, BF and CN diets. Plasma total cholesterol levels were significantly higher in rats fed the PO and BT diets than in rats fed the BF and CN diets but were not different among the PO-, BT- and CO-fed groups. Nondenaturing gradient gel electrophoresis immunoblot analysis indicated that HDL apo A-I and E resided on particles with significantly smaller modal diameters in rats fed all saturated fats compared with those fed the CO diet. Chemical analyses indicated that HDL generally contained proportionately less protein and more triglyceride, free cholesterol and apo E with saturated fat feeding than with CO diet feeding. Significantly higher plasma and VLDL triglyceride levels were noted with ingestion of the BT, PO or CN diet than with the CO diet. Butterfat feeding resulted in lower plasma triglycerides and HDL-esterified cholesterol than did feeding the other saturated fats. Very low density lipoprotein triglyceride concentrations were inversely correlated with HDL modal diameter of apo E containing lipoproteins (P less than 0.005). These data provide further evidence of the interrelationship of triglyceride and HDL metabolism and suggest that mechanisms independent of cholesterol ester transfer protein may mediate this response in rats.     

Influence of dietary fats and vitamin E on plasma and hepatic vitamin A and beta-carotene levels in rats fed excess beta-carotene

Effects of different dietary lipids and excess vitamin E on plasma and hepatic concentrations of beta-carotene were evaluated in rats fed diets containing a large excess (0.2%) of beta-carotene. Male weanling Wistar Kyoto rats were fed beta-carotene-supplemented diets containing various dietary lipids as follows: Group I, a saturated fat (coconut oil); Group II, a monounsaturated fat (olive oil); Group III, a polyunsaturated fat rich in omega-6 fatty acids (safflower oil); Group IV, same as Group III plus vitamin E; and Group V, a polyunsaturated fat rich in omega-3 fatty acids (menhaden oil). All diets contained 2% safflower oil to provide sufficient amounts of linoleic acid (an essential fatty acid). Rats were killed after six weeks of feeding the various diets, and the concentrations of beta-carotene and vitamin A were determined in plasma and liver. Plasma vitamin A levels were not altered by any of the dietary lipids or by an excess of vitamin E. The concentrations of beta-carotene in plasma were the lowest in rats fed the diet containing menhaden oil. The feeding of the diet containing an excess of vitamin E also resulted in a significant decrease in plasma beta-carotene concentration. Similarly, the hepatic beta-carotene concentration was also reduced to about one-half in rats fed the diet containing an excess of vitamin E. Liver beta-carotene concentration was higher in Groups II and III than in the other three dietary groups. Hepatic vitamin A concentrations were also affected by the type of dietary fat.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of dietary fats (fish, olive and high-oleic-acid sunflower oils) on lipid composition and antioxidant enzymes in rat liver

The effects of two oleic-acid-rich diets (containing olive oil, OO, and high-oleic-acid sunflower oil, HOSO) on plasma and liver lipid composition detoxification enzyme activities, were compared with those of a fish-oil (FO) diet and a control diet. Compared with the control diet, plasma and hepatic total triacylglycerol concentrations were increased in the animals fed on the HOSO and OO diets and decreased in those fed on the FO diet. The animals fed on FO showed the highest level of cholesterol in the liver and had lower plasma cholesterol concentrations when compared with those fed on the two oleic-acid-rich diets. In comparison with the animals fed on the diets enriched in oleic acid, the FO group showed higher hepatic levels of polyunsaturated fatty acids of the n-3 series and lower levels of fatty acids of the n-6 series. Livers of FO-fed rats, compared with those of OO- and HOSO-fed rats showed: (1) significantly higher activities of catalase (EC 1.11.1.6) glutathione peroxidase (EC 1.11.1.9) and Cu/Zn superoxide dismutase (EC 1.15.1.1); (2) no differences in the NADPH-cytochrome c reductase (EC 1.6.99.3) 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. The two monounsaturated fatty acids oils studied (OO and HOSO), with the same high content of oleic acid but different contents of natural antioxidants, had similar effects on the antioxidant enzyme activities measured.     

Ca2+-Mg2+ ATPase of mouse cardiac sarcoplasmic reticulum is affected by membrane n-6 and n-3 polyunsaturated fatty acid content

White mice, 18-20 g, were fed purified diets containing two weight percent safflower oil plus ten weight percent menhaden, corn, or olive oil for 2 wk. Menhaden oil ingestion resulted in significantly higher levels of 22:6(n-3) and 20:5(n-3), particularly 22:6(n-3), and lower levels of 20:4(n-6) and 18:2(n-6) in cardiac sarcoplasmic reticulum (SR) phospholipids than did corn or olive oil ingestion. These changes in fatty acid composition resulted in a significant decrease in the value of the n-6/n-3 fatty acid ratio of cardiac SR phospholipids. The ratio was 2.8 versus 0.2 in choline phospholipids and 1.9 versus 0.2 in ethanolamine phospholipids in SR of mice fed corn or menhaden oil, respectively. This reduction in the n-6/n-3 fatty acid ratio was associated with a lower relative activity of Ca2+-Mg2+ ATPase, and a lower initial rate of calcium transport and maximum calcium uptake in SR vesicles from mice fed menhaden oil rather than olive or corn oils. The specific activity of NADPH cytochrome C reductase (EC 1.6.2.3) of cardiac SR was not affected by dietary lipids. These data indicate that modification of SR by 22:6(n-3) may change the SR bilayer structure resulting in alteration of the calcium transport properties of SR vesicles. In addition, our results suggest that reduction of calcium flux across cardiac SR following fish oil consumption may also reduce the susceptibility of myocytes to rapid changes in calcium concentrations which may occur during ischemia and reperfusion.     

Dose-response relationships between dietary (n-3) fatty acids and plasma and tissue lipids, steroid excretion and urinary malondialdehyde in rats.

For a 28-d experimental period, rats were fed a nonpurified, cereal-based diet containing 9.1% supplemental beef tallow or fish oil or one of the following beef tallow:fish oil blends: 95:5; 90:10; 80:20 and 50:50. All diets provided between 21.3 and 22.7 g linoleic acid/kg. Higher fish oil intake was paralleled by elevated incorporation of long-chain (n-3) fatty acids in plasma total lipid, mainly at the expense of arachidonic acid. Significant inverse relationships were found between plasma total (n-3) fatty acid concentration and plasma triglyceride, cholesterol or free fatty acid concentrations. Fish oil intake did not lead to a shift of triglycerides or cholesterol from the plasma to the tissues (liver, heart, kidneys). Reduced plasma cholesterol concentrations in the fish oil-fed rats could not be explained by higher fecal excretion of neutral sterols and bile acids. In vivo lipid peroxidation, assessed by urinary malondialdehyde excretion, was enhanced when diets containing greater than 1.8% fish oil were fed.     

Effect of dietary fat on hepatic metabolism of 14C-oleic acid and very low density lipoprotein triglyceride in the gerbil.

In order to compare in vitro and in vivo aspects of lipid metabolism and lipoprotein secretion associated with the hyperlipemia of saturated fat feeding, gerbils were fed a diet containing 15% coconut oil or safflower oil for 6 weeks. In vitro incorporation of fatty acid was determined by measuring 14C-oleic acid incorporation into hepatic lipis in liver fasting gerbils following Triton WR1339 injection. The plasma lipoprotein profile was assessed by agarose electrophoresis. Coconut oil produced a hypertriglyceridemia and hypercholesterolemia associated with the appearance of very low density migrating lipoprotein, not seen with the safflower oil. Coconut oil also increased the hepatic triglyceride content, enhanced 14C-oleic acid incorporation into total lipid, and favored fatty acid incorporation into triglyceride; safflower oil facilitated esterification of oleic acid into phospholipid. Triton blockade of gerbils fed safflower oil resulted in twice the triglyceride secretion rate of those fed coconut oil. Our interpretation of the data is that dietary polyunsaturated fat favors incorporation of fatty acids into phospholipid, enhances both triglyceride secretion and the plasma transport and clearance of triglyceride and cholesterol and that the hyperlipemia of coconut oil feeding reflects a reduced metabolic clearnace of circulating lipid associated with that dietary fat.     

Docosahexaenoic acid-rich fish oil and pectin have a hypolipidemic effect, but pectin increases risk factor for colon cancer in rats

This study was designed to compare the effect of fish oil rich in DHA and pectin on the level of plasma lipids, hepatic HMG CoA reductase activity, microsomal membrane fluidity, colonic luminal content of short chain fatty acids (SCFA) and fecal excretion of bile acids and neutral sterols in rats. Male SD rats (7wks) were divided into three groups according to dietary fat sources, beef tallow (BT), corn oil (CO), fish oil (FO) and each group was subdivided into cellulose and pectin groups. The rats were fed for 25 wks the experimental diet containing 15% fat and 6% fiber and all rats were intramuscularly injected. with DMH. FO significantly reduced the levels of plasma Chol, TG, LDL-C, VLDL-C and hepatic HMG CoA reductase activity and increased membrane fluidity as compared with BT and CO. Pectin significantly reduced the levels of plasma Chol, VLDL-C and LDL-C, but increased HDL-C, HMG CoA reductase activity and membrane fluidity (p<0.05). However, pectin significantly increased the luminal content of butyrate and propionate in CO-fed rats and increased fecal excretion of deoxycholic acid and lithocholic acid in BT and CO-fed rats (p<0.05). Overall, fish oil had a protective effect against CVD by inhibiting hepatic HMG CoA reductase activity and increasing hepatic microsomal fluidity, thus leading to a reduction in plasma lipids. Pectin also had a protective effect against CVD by increasing fecal excretion of neutral sterols and hepatic microsomal fluidity. Pectin, however, increased risk factors for colon cancer by increasing the production of secondary bile acids and SCFA in the colon.     

Accelerative effect of olive oil on adrenal corticosterone secretion in rats loaded with single or repetitive immersion-restraint stress

The present study was performed to clarify the effects of dietary oils on physiological and metabolic changes induced by a stress, using one-time or repetitive water-immersion of restrained rats (single or repetitive stress) as an experimental stress load. In rats fed any test diets containing 20%) of the mixture of tripalmitin, tristearin, and corn oil (PSC), olive oil (OLI). safflower oil (SAF), and linseed oil (LIS) with repetitive stress loading, body weight gains and food intakes were generally reduced. The weights of the thymus and spleen also declined, but the adrenal weights were enhanced. Particularly, the increase in the adrenal weight of rats given the OLI diet was greater than of rats supplied with other diets. When the rats were loaded with the single or repetitive stress, the concentrations of urea, lipid peroxide, and corticosterone in the plasma were increased in rats fed any of dietary oils. The rise of plasma corticosterone level was especially great in rats fed the OLI diet. The concentrations of total cholesterol (T-CHOL) and triglyceride (TG) in the plasma and liver generally tended to be higher in rats fed the OLI diet than in rats given the other diets with and without stress exposure. Plasma corticosterone concentration was correlated to the adrenal weight (r=0.87, p<0.05). This study showed that OLI especially enhanced the adrenal weight in rats exposed to the repetitive stress and further raised the increased secretion of adrenal corticosterone in rats loaded with the single or repetitive stress compared with the other oils. The mechanism explaining these actions of OLI was inferred to be related to the levels of T-CHOL and TG in the plasma and liver generally enhanced by stress.