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

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

Effect of excessive intake of thermally oxidized sesame oil on lipids,lipid peroxidation and antioxidants' status in rats

Fresh and thermally oxidized sesame, groundnut and coconut oils were fed to different groups of rats, as high fat diet (20%). Feeding fresh and thermally oxidized oils increased the levels of total cholesterol, low density lipoprotein cholesterol (LDL-C), and phospholipids but high density lipoprotein cholesterol (HDL-C) decreased in all the experimental animals. The levels of very low density lipoproteincholesterol (VLDL-C) and triacylglycerol increased only in groundnut and coconut oils-fed groups and decreased in sesame oil-fed group when compared with the control. When fresh and the corresponding thermally oxidized oils-fed groups were compared with the control, total cholesterol and LDL-cholesterol alone increased while triacylglycerol, VLDL-cholesterol, HDL-cholesterol, HDL/LDL ratio and phospholipids decreased. Thiobarbituric acid reacting substances increased in all the experimental animals and more so in corresponding thermally oxidized oils. It was less pronounced in sesame oil-fed groups when compared with the corresponding other oils-fed groups. Feeding of thermally oxidized oils decreased the levels of vitamin E, vitamin C and reduced glutathione when compared with fresh oils. Among the three thermally oxidized edible oils, sesame oil exhibited lesser risk for hyperlipidemic disorders.     

Effect of fish oil and coconut oil diet on the LDL receptor activity of rat liver plasma membranes

The influence of 4 weeks treatment with fish oil and coconut oil enriched diets on the chemical composition of rat liver plasma membranes and LDL and on the binding of LDL to liver membranes was investigated. Rats fed fish oil diet showed a total, LDL and HDL plasma cholesterol concentration lower than the values observed in rats fed coconut oil and to a lesser extent lower than those of rats fed standard laboratory diet. LDL of rats on fish oil diet had a relative percentage of cholesterol and phospholipid lower, while that of triacylglycerol was greater. Furthermore, fish oil feeding was associated with a greater concentration of n - 3 fatty acids and a lower arachidonic and linoleic acid content in LDL. Liver plasma membranes isolated from fish oil rats showed a higher percentage of n - 3 fatty acids, while only a trace amount of these fatty acids was found in control and coconut oil fed animals. In binding experiments performed with LDL and liver membranes from fish oil fed rats and control rats, binding affinity (Kd = 3.47 +/- 0.93 and 4.56 +/- 1.27, respectively) was significantly higher (P less than 0.05) as compared to that found using membranes and lipoprotein from coconut oil fed rats (Kd = 6.82 +/- 2.69). In cross-binding experiments performed with fish oil LDL and coconut oil liver plasma membranes or coconut oil LDL and fish oil liver plasma membranes, the LDL binding affinity was comparable and similar to that found in fish oil fed animals. No difference was found in the Bmax among all the groups of binding experiments. Our data seem to indicate that during fish oil diet the higher binding affinity of LDL to liver plasma membranes might be partly responsible of the hypocholesterolemic action of marine oil rich diet as compared to saturated diet. Furthermore, the modifications of binding affinity induced by changes of LDL and membrane source, suggest that lipoprotein and liver plasma membrane composition may be an important variable in binding studies.     

Fish oil reduces cholesterol and arachidonic acid levels in plasma and lipoproteins from hypercholesterolemic chicks

The value of fish oil for prevention and/or treatment of human atherosclerosis has not been fully established. This study shows that replacement of saturated fat in young chick diet with menhaden oil produced a significant reversion of the hypercholesterolemia previously induced by coconut oil feeding. Fish oil also produced a clear decrease of plasma triacylglycerol levels. Coconut oil increased the percentages of 12:0 and 14:0 fatty acids, while menhaden oil increased those of 20:5 n-3 and 22:6 n-3. Percentages of 20:4 n-6, 18:2 n-6 and 18:1 n-9 significantly decreased by fish oil addition to the diet. Total cholesterol, phospholipid and protein contents of high and low density lipoproteins increased by coconut oil feeding. When coconut oil was replaced by menhaden oil, total cholesterol was significantly reduced in high, low and very low density lipoproteins. All chemical components of VLDL were decreased by menhaden oil feeding. Our results show a strong hypocholesterolemic effect of menhaden oil when this fat was supplemented to hypercholesterolemic chicks. The clear decrease found in arachidonic acid content of chick plasma and lipoproteins may contribute to the beneficial effects of fish oil consumption by lowering the production of its derived eicosanoids.     

Changes in plasma lipid composition induced by coconut oil. Effects of dipyridamole

The comparative effects of 10-20% coconut oil feeding on fatty acid composition of the main lipid classes of chick plasma have been studied with and without simultaneous treatment with dipyridamole in order to clarify the hypolipidemic role of this drug. Coconut oil drastically increased the percentages of lauric and myristic acids in free fatty acid and triacylglycerol fractions, whereas these changes were less pronounced in phospholipids and cholesterol esters. The percentage of arachidonic acid was higher in plasma phospholipids than in the other fractions and was significantly decreased by coconut oil feeding. Linoleic acid, the main fatty acid of cholesterol esters, was drastically increased by coconut oil feeding. Changes induced by the simultaneous administration of dipyridamole were more pronounced in the phospholipids and cholesterol esters than in the other fractions. The fall observed in linoleic acid levels after dipyridamole treatment may be of interest for a lower production of its derived eicosanoids, especially in plasma phospholipids and cholesterol esters.     

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.     

Supplementation of orotic acid to the casein, but not to egg protein, soy protein, or wheat gluten diets, increases serum ornithine carbamoyltransferase activity

Effects of dietary supplementation of orotic acid to a diet containing the casein protein were compared with diets containing egg protein, soy protein, or wheat gluten on lipid levels in the liver and serum and activities of ornithine carbamoyltransferase (OCT) and alanine aminotransferase in the serum of rats. We found that supplementation of orotic acid to each diet increased the contents of the liver total lipids, triacylglycerol, and phospholipids compared with those not supplemented. The contents of liver total lipids, triacylglycerol, cholesterol, and phospholipids in rats fed the casein diet were significantly higher than those of rats fed the other three diets when orotic acid was supplemented. The levels of triacylglycerol, cholesterol, and phospholipids in the serum of rats fed the casein diet were markedly decreased by addition of orotic acid. The supplementation of orotic acid significantly increased the activities of both serum OCT and alanine aminotransferase in rats fed the casein diet, but not in rats fed the other diets. In conclusion, liver lipid accumulation induced by dietary orotic acid depends on the type of dietary protein. The enhancement of serum OCT activity may result from liver lipid accumulation in rats fed the casein diet supplemented with orotic acid, demonstrating hepatic damage.     

Hepatic expression of apolipoprotein A-I gene in rats is upregulated by monounsaturated fatty acid diet

The effect of the degree of dietary fat saturation on the hepatic expression of apolipoprotein A-I mRNA was studied in male rats. Animals were maintained for two months on a high fat diet (40% w/w) containing 0.1% cholesterol. Two groups of control animals received either chow diet or chow plus 0.1% cholesterol, while experimental groups received their fat supplement as coconut, corn or olive oil respectively. Dietary cholesterol did not affect apolipoprotein A-I mRNA levels as compared to control animals. Corn oil fed animals had significantly higher levels of hepatic apolipoprotein A-I mRNA than those receiving cholesterol, or coconut oil plus cholesterol. Olive oil fed animals had significantly higher levels of hepatic apolipoprotein A-I mRNA when compared to all other dietary groups. Our data indicate that monounsaturated fatty acids supplied as olive oil play a major role in regulating the hepatic expression of apolipoprotein A-I in male rats.     

Nutritional evaluation of structured lipid containing omega 6 fatty acid synthesized from coconut oil in rats

Coconut oil is rich in medium chain fatty acids, but deficient in polyunsaturated fatty acids (PUFA). Structured lipids (SL) enriched with omega 6 PUFA were synthesized from coconut oil triglycerides by employing enzymatic acidolysis with free fatty acids obtained from safflower oil. Rats were fed a diet containing coconut oil, coconut oil-safflower oil blend (1:0.7 w/w) or structured lipid at 10% levels for a period of 60 days. The SL lowered serum cholesterol levels by 10.3 and 10.5% respectively in comparison with those fed coconut oil and blended oil. Similarly the liver cholesterol levels were also decreased by 35.9 and 26.6% respectively in animals fed structured lipids when compared to those fed on coconut oil or the blended oil. Most of the decrease observed in serum cholesterol levels of animals fed structured lipids was found in LDL fraction. The triglyceride levels in serum showed a decrease by 17.5 and 17.4% while in the liver it was reduced by 45.8 and 23.5% in the structured lipids fed animals as compared to those fed coconut oil or blended oil respectively. Differential scanning calorimetric studies indicated that structured lipids had lower melting points and solid fat content when compared to coconut oil or blended oils. These studies indicated that enrichment of coconut oil triglycerides with omega 6 fatty acids lowers its solid fat content. The omega 6 PUFA enriched structured lipids also exhibited hypolipidemic activity.     

Differential effects of dietary fat on chick plasma and liver composition and HMG-CoA reductase activity

The comparative effects of diet supplementation with 10% saturated fat rich in 12:0 and 14:0 fatty acids (coconut oil), without and with 1% added cholesterol, and with 10% unsaturated fat rich in n-3 polyunsaturated fatty acids (menhaden oil) on cholesterol metabolism in neonatal chicks were examined to clarify the different mechanisms of their hyper- and hypolipidemic action. Supplementation of coconut oil produced a significant hypercholesterolemia after 7 days of treatment, with a similar increase in the amount of both free and esterified cholesterol. Supplementation of coconut oil plus cholesterol produced a higher increase of plasma cholesterol levels (approximately two to three times higher than those found with standard diet). However, supplementation of menhaden oil induced a significant decrease in total cholesterol after only 2 weeks of treatment. Levels of plasma triglycerides did not change by coconut oil addition to the diet, but a significant increase was observed after coconut oil plus cholesterol feeding. Menhaden oil produced a transient decrease in plasma triglycerides. Hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity did not change with coconut oil treatment. However, both coconut oil plus cholesterol and menhaden oil supplemented diets drastically decreased reductase activity after 1 week of dietary manipulation. These results show that different nutrients with the same inhibitory effect on reductase activity produced opposite effects on plasma cholesterol content, suggesting the existence of important differences in the regulatory mechanisms implied in cholesterol biosynthesis and its accumulation in plasma.     

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.     

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

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

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.     

Hypolipidemic and antiperoxidative effect of coconut protein in hypercholesterolemic rats

Effect of coconut protein in rats fed high fat cholesterol containing diet on the metabolism of lipids and lipid peroxides was studied. In addition, effect of coconut protein were compared with rats fed L-arginine. The results indicate that those fed coconut protein and those fed L-arginine showed significantly lower levels of total cholesterol, LDL+ VLDL cholesterol, Triglycerides and Phospholipids in the serum and higher levels of serum HDL cholesterol. The concentration of total cholesterol, triglycerides and phospholipids in the tissues were lower in these groups. There was increased hepatic cholesterogenesis which is evident from the higher rate of incorporation of labeled acetate into free cholesterol. Increased conversion of cholesterol to bile acids and increased fecal excretion of bile acids were observed. Feeding coconut protein results in decreased levels of Malondialdehyde in the heart and increased activity of Superoxide dismutase and Catalase. Supplementation of coconut protein causes increased excretion of urinary nitrate which implies higher rate of conversion of arginine into nitric oxide. In the present study, the arginine supplemented group and the coconut protein fed group produced similar effects. These studies clearly demonstrate that coconut protein is able to reduce hyperlipidemia and peroxidative effect induced by high fat cholesterol containing diet and these effects are mainly mediated by the L-arginine present in it.     

Steroid balance and tissue cholesterol accumulation in germfree and conventional rats fed diets containing saturated and polyunsaturated fats

Steroid balance studies were conducted on 24 conventional and 12 germfree male rats, 90-120 days old, fed diets containing either 20% safflower or 20% coconut oil. Both germfree and conventional rats fed the safflower oil diets had significantly lower serum cholesterol levels and significantly higher liver cholesterol levels than did the rats fed coconut oil. No significant differences in total fecal neutral sterols, coprostanol, Delta(7)-cholestenol, or total fecal bile acid excretion were seen between dietary groups of rats of either status. There was no evidence of qualitative differences in fecal bile acid excretion as a function of diet. The increased liver cholesterol was in the ester form, with cholesteryl linoleate the largest single component. There was no significant difference in the cholesterol content of the skin, muscle, adipose tissue, or gastrointestinal tract. The significance of a large increase in liver cholesteryl ester, lowered serum cholesterol, and no change in steroid excretion is discussed.     

The influence of dietary vitamin E, fat, and methionine on blood cholesterol profile, homocysteine levels, and oxidizability of low density lipoprotein in the gerbil

A 90-day feeding study with gerbils was conducted to evaluate the influence of dietary vitamin E levels (25 mg/kg diet, 75 mg/kg, 300 mg/kg, and 900 mg/kg), two levels of dietary methionione (casein or casein+L-methionine (1% w/w)) and two sources of lipid (soybean oil [20%] or soybean oil [4%]+coconut oil [16%, 1:4 w/w]) upon serum lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol). In addition, this study examined the effects of diet-induced hyperhomocysteinemia and supplemental dietary vitamin E on the oxidation of low density lipoproteins. Tissue vitamin E (heart, liver, and plasma) demonstrated a dose response (P≤0.001) following the supplementation with increasing dietary vitamin E (25, 75, 300, and 900 mg/kg). In addition, tissue vitamin E levels were found to be higher (P≤0.001) in those animals receiving a combination of coconut oil+soybean oil as compared to the group receiving soybean oil solely. Blood cholesterol profiles indicated an increase (P≤0.001) in total cholesterol and LDL cholesterol by the influence of saturated fat and supplemental methionine. Low-density lipoprotein cholesterol profile demonstrated a reduction (P≤0.001) at the higher dietary vitamin E levels (300 and 900 mg/kg) as compared to the 25 mg/kg and 75 mg/kg dietary vitamin E. Plasma protein carbonyls were not influenced by dietary vitamin E nor by supplemental methionine intake. In vitro oxidation of LDL showed that vitamin E delayed the lag time of the oxidation phase (P≤0.001) and reduced total diene production (P≤0.001). On the contrary, supplemental methionine decreased (P≤0.001) the delay time of the lag phase, whereas total diene production was increased (P≤0.001). Plasma lipid hydroperoxides were significantly reduced (P≤0.05) with supplemental dietary vitamin E, whereas supplemental L-methionine (1%) resulted in a significant (P≤0.05) increase in lipid plasma hydroperoxide formation. Plasma homocysteine was elevated (P≤0.001) with supplemental dietary L-methionine (1%) as well as the inclusion of dietary saturated fat. The present data showed that 1) a combination of dietary lipids (saturated and unsaturated fatty acids) as well as vitamin E and methionine supplementation altered blood cholesterol lipoprotein profiles; 2) in vitro oxidation parameters including LDL (lag time and diene production) and plasma hydroperoxide formations were affected by vitamin E and methionine supplementation; and 3) plasma homocysteine concentrations were influenced by supplemental methionine and the inclusion of dietary saturated fat.     

Superiority of dietary safflower oil over olive oil in lowering serum cholesterol and increasing hepatic mRnas for the LDL receptor and cholesterol 7alpha-hydroxylase in exogenously hypercholesterolemic (exHC) rats

The exogenously hypercholesterolemic (ExHC) rat is a strain segregated from SD rats with a high response to dietary cholesterol. To understand the underlying mechanism(s) for this hypercholesterolemia, the interactive effects of dietary fatty acid and the susceptibility of rats to dietary cholesterol on the serum cholesterol concentration and hepatic mRNA abundance of the low-density lipoprotein (LDL) receptor, cholesterol 7alpha-hydroxylase (7alpha-hydroxylase) and 3-hydroxyl-3methylglutaryl (HMG) CoA reductase were examined. Both strains were fed on a diet supplemented with 10% each of olive, safflower or coconut oil with or without the addition of 1% cholesterol for one week. The ExHC rats fed on olive, safflower and coconut oil in combination with cholesterol respectively resulted in a 3.5-, 2.0- and 2.1-fold higher serum cholesterol concentration than that in the animals fed on the corresponding dietary fats without any supplementation of cholesterol (p < 0.01 by dietary cholesterol or type of fat). The dietary cholesterol dependent-elevation of serum cholesterol in the SD rats was less than 1.5-fold (p<0.01) and there was no dietary fat effect. The ExHC rats fed on the safflower oil-containing diet supplemented with cholesterol resulted in a higher mRNA abundance of the LDL receptor and 7alpha-hydroxylase than in the corresponding fat-fed rats without cholesterol (p<0.05). There was no dietary cholesterol-dependent change of mRNA abundance in either strain fed on olive or coconut oil, except for a decreased abundance of HMG CoA reductase mRNA in the olive oil-fed ExHC rats and coconut oil-fed Sprague-Dawley (SD) rats (p<0.05). These results indicate that the hepatic mRNA abundance of the LDL receptor and of 7alpha-hydroxylase depended on the dietary combination of cholesterol and a fatty acid and suggest that a linoleic acid-rich diet may alleviate exogenous hypercholesterolemia by activating the process involved in the hepatic uptake and biliary excretion of serum cholesterol.     

Effects of Sterylglycosides from Soybean on Lipid Indices in the Plasma,Liver, and Feces of Rats

The effects of soybean oil (SOO, control), soybean lecithin (SOL), and of sterylglycocides (STG) and phospholipids (PL) fractionated from SOL on lipid indices in the plasma, liver, and feces were examined for male Wistar rats fed with diets containing these lipids for 3 weeks. The body weight gain and liver weight decreased or tended to be reduced in the animals given the diet containing a 5% STG mixture (STGM) compared with the values in the other dietary groups. The plasma lipid concentration in general declined in the rats fed with the diets supplemented with 5% SOL, STGM, or the PL mixture (PLM), and with 1% of STGM, acylated STG (ASTG), or non-acylated STG (NSTG). The triacylglycerol level was significantly depressed in the rats fed with the diets including 1 or 5% of STGM, ASTG, or NSTG when compared to the level of the SOO—fed animals. The total cholesterol and triacylglycerol contents in the liver were lower in the rats provided with the diets containing 5% of SOL, PC, or PLM than in the SOO- or STGM-diet-fed animals. The rats given the diets supplemented with 1 or 5% of STGM, ASTG, or NSTG had a decreased content of liver triacylglycerol compared with the content of the SOO—fed animals. The amounts of total lipids and total cholesterol excreted into the feces were higher in the rats fed with the diets supplemented with 5% SOL, or with 1% of STGM, ASTG, or NSTG, or especially with 5% STGM than in the SOO—fed animals. The present results suggest that STG suppressed the absorption of cholesterol and fatty acids in the intestines.     

Effect of methotrexate on long-chain fatty acid metabolism in liver of rats fed a standard or a defined, choline-deficient diet

The effect of methotrexate on lipids in serum and liver and key enzymes involved in esterification and oxidation of long-chain fatty acids were investigated in rats fed a standard diet and a defined choline-deficient diet. Hepatic metabolism of long-chain fatty acids were also studied in rats fed the defined diet with or without choline. When methotrexate was administered to the rats fed the standard diet there was a slight increase in hepatic lipids and a moderate reduction in the serum level. The palmitoyl-CoA synthetase activity and the microsomal glycerophosphate acyltransferase activity in the liver of rats were increased by methotrexate. The data are consistent with those where the liver may fail to transfer the newly formed triacylglycerols into the plasma with a resultant increase in liver triacylglycerol content and a decrease in serum lipid levels. Fatty liver of methotrexate-exposed rats can not be attributed simply to a reduction of fatty acid oxidation as the carnitine palmitoyltransferase activity was increased. The methotrexate response in the rats fed the defined choline-deficient diet was different. There was a reduction in both serum and hepatic triacylglycerol and the glycerophosphate acyltransferase and palmitoyl-CoA synthetase activities. The carnitine palmitoyltransferase activity was unchanged. Hepatomegaly and increased hepatic fat content, but decreased serum triacylglycerol, total cholesterol and HDL cholesterol were found to be related to the development of choline deficiency as the pleiotropic responses were almost fully prevented by addition of choline to the choline-deficient diet. Addition of choline to the choline-deficient diet normalized the total palmitoyl-CoA synthetase and carnitine palmitoyltransferase activities. In contrast to methotrexate exposure, choline deficiency increased the mitochondrial glycerophosphate acyltransferase activity. The data are consistent with those of where fatty liver induction of choline deficiency may be related to an enhanced esterification of long-chain fatty acids concomitant with a reduction of their oxidation.     

Different response to choline deficiency of the serum ornithine carbamoyltransferase activity in four strains of rats

Rats of the Donryu, Wistar, Fischer, and Sprague-Dawley strains were examined for the effects of choline deficiency on liver lipids, serum lipids, and serum ornithine carbamoyltransferase. The liver total lipid, triacylglycerol, cholesterol and phospholipid contents in the choline-deficient rats were significantly higher than those in choline-sufficient rats. The contents of total lipids and phospholipids in the liver of the Wistar and Fischer rats fed on a choline-deficient diet were significantly higher than those of the Donryu and Sprague-Dawley rats. The levels of triacylglycerol, cholesterol and phospholipids in the serum were significantly decreased by feeding with the choline-deficient diet. The serum ornithine carbamoyltransferase activity was increased in the Wistar and Fischer strains by feeding with the choline-deficient diet. The Wistar and Fischer strains were consequently the most sensitive to both lipid accumulation and liver lesions induced by the choline deficiency.