Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on de novo fatty acid and cholesterol synthesis in the rat

The effects of 1, 5, 10 and 20 μg/kg dosages of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) upon de novo fatty acid and cholesterol synthesis in liver and adipose tissue were determined in pair-fed rats. The incorporation of tritium from³H₂O into tissue lipids was measured. Hepatic and adipose fatty acid synthetic rates (μmoles acetyl units g⁻¹ hr⁻¹ in the control groups were 19.6±4 and 75.7±18.5, respectively, and the liver cholesterol synthetic rate was 2.9±0.5 TCDD (1 μg/kg) inhibited fatty acid synthesis in the liver and adipose tissue, by 44% and 41% respectively, and the liver cholesterol synthesis was inhibited by 37%. The extent of these inhibitions increased with increasing dosages of TCDD. The effect of TCDD on sterol synthesis in adipose tissue could not be determined, because the tritium incorporation into the sterol fraction in this tissue was not detectable.     

飞灰酸碱性对二噁英从头合成的影响

飞灰表面的酸碱性对二噁英的从头合成反应影响较大,不仅能够改变二噁英的生成量,而且对二噁英同分异构体的分布也存在一定的影响。本文通过在实验室可控条件下添加不同比例的Ca(H₂PO₄)₂和CaO酸碱性物质,改变模拟飞灰表面的pH,研究不同酸碱性对二噁英从头合成反应的影响。研究表明,添加5%(质量)的Ca(H₂PO₄)₂时,飞灰表面的pH由原始的5.5下降至4.3,二噁英总量增加,而毒性当量基本不变;添加20%(质量)的Ca(H₂PO₄)₂时,pH降低到3.6,生成的二噁英总量和毒性当量均下降;而添加0.4%(质量)、5%(质量)和20%(质量)的CaO调节pH至9.8、12.4和12.6时,二噁英总量及毒性当量均有减少。因此,飞灰表面碱性环境较酸性环境对二噁英从头合成反应的抑制效果好。此外,本文还研究实际焚烧炉飞灰中二噁英总量与碱酸比的相关性,结果表明流化床飞灰中二噁英总量与碱酸比的相关系数高达0.95,而炉排炉飞灰中两者之间不存在相关性。     

Effects of essential fatty acid deficiency on prostaglandin synthesis and fatty acid composition in rat renal medulla

Studies are reported on the capacity of isolated rat renal papilla (inner medulla) to synthesize and release prostaglandin (PG) E from endogenous and exogenous precursor(s) during development of an essential fatty acid (EFA) deficiency in the rat. Weanling (21-day-old) male Sprague-Dawley rats were fed a fat-free diet supplemented with either 5% hydrogenated coconut oil (HCO) or 5% safflower oil (SO). At approximately 3, 6 and 7 weeks (6, 9 and 10 weeks of age), groups of animals fed each diet were killed for studies of PGE synthesis in the renal papillae. Differences in the fatty acid composition of the papillae lipids of the animals of each group were also determined. The in vitro production of PGE from endogenous precursor(s) was significantly reduced in the papillae from the 6-week-old rats fed the HCO diet compared to the control (SO) rats, and appeared to be near maximally depressed in the 10-week-old animals compared to that of animals fed an EFA deficient diet for over a year in an accessory experiment. Analyses of the fatty acids of the papillae lipids of the HCO groups showed that the levels of 18∶2 and 20∶4 were markedly reduced, and those of 16∶1, 18∶1 and 20∶3 were elevated compared to the controls even in the 6-week-old animals, typical of an EFA deficiency. The papillae lipids of the animals fed the HCO diet were also depleted of their stores of 22∶4ω6. A fatty acid believed to be derived by chain elongation of 20∶3ω9, 22∶3, was found in large concentrations in the papillae triglycerides of the EFA deficient rats. Incubations of exogenous arachidonic acid (20∶4) in homogenates and tissue slices of the papillae of the HCO dietary groups showed that the PG synthetase was not impaired by an EFA deficiency. The rate of PGE synthesis in the papillae of the EFA deficient animals was generally enhanced when exogenous 20∶4 was added, indicating that the concentration of available precursor(s) is a primary factor in the control of PGE synthesis in the papilla of the rat.     

Effects of non-β-oxidizable sulfur-substituted fatty acid analogues on synthesis and secretion of triacylglycerol and cholesterol in cultured rat hapatocytes

The mechanisms behind the hypolipidemic effect of two sulfur-substituted fatty acid analogues, 3-thiadicarboxylic acid and tetradecylthioacetic acid, have been investigated in cultured hepatocytes. There was a dose-dependent reduction in incorporation of [³H]water into triacylglycerol and diacylglycerol when tetradecylthioacetic acid was added to rat hepatocytes cultured in the presence of 200 μM oleic acid. Tetradecylthioacetic acid also increased the oxidation of [¹⁴C]palmitic acid compared to oleic acid, inhibited the incorporation of radiolabeled precursors into diacylglycerol to a greater extent than into triacylglycerol, and reduced the secretion of triacylglycerol more than its synthesis. A stimulation, rather than a reduction, in glycerolipid synthesis and secretion by tetradecylthioacetic acid was observed when oleic acid was omitted from the culture medium. When 3-thiadicarboxylic acid was added to cultured hepatocytes, the effects on glycerolipid synthesis were generally similar to those observed with tetradecylthioacetic acid, but 3-thiadicarboxylic acid did not increase the oxidation of [¹⁴C]palmitic acid. The two fatty acid analogues also had different effects on the synthesis and secretion of cholesterol and cholesteryl esters—3-thiadicarboxylic acid reduced the incorporation of [³H]water into synthesized and secreted cholesterol and cholesteryl esters, whereas tetradecylthioacetic acid only reduced the secretion of cholesteryl esters without affecting its synthesis. It is concluded that tetradecylthioacetic acid increases the oxidation of fatty acids and reduces the synthesis and secretion of glycerolipids. 3-Thiadicarboxylic acid reduces the synthesis and secretion of both glycerolipids and cholesterol to approximately the same extent without a concomitant increase in the oxidation of fatty acids.     

De novo fatty acid synthesis and fatty acid elongation catalyzed by subcellular fractions from hog and human aorta

De novo synthesis and mitochondrial elongation of fatty acids have been demonstrated in subcellular fractions from hog and human aorta. Microsomal fatty acid elongation has been shown in hog aorta. The activity catalyzing the formation of fatty acids from acetyl and malonyl CoA was associated with a high molecular weight complex in the 6×10⁶g×min supernatant fraction. The principal product was palmitic acid. Some myristic and stearic acids were also formed. One elongation system was associated with protein which sedimented between 4500 g×min and 150,000 g×min. It used acetyl CoA but not malonyl CoA, and NADH was the preferred reducing agent. Radioactivity from acetyl CoA was incorporated into many fatty acids. In hog aorta a second elongation system was found associated with protein which sedimented at 6×10⁶ g×min. It used malonyl CoA preferentially as substrate and either NADH or NADPH as reducing agent.     

Dietary lipid,fatty acid synthesis and cholesterol metabolism in aging rats

Male and female rats were fed diets containing 2% of calories as corn oil or that plus 40% of calories as beef tallow or corn oil. After 3, 6, 12 and 18 months groups were given 4-¹⁴C-cholesterol ip, and feces were collected for 9 days. Just prior to necropsy³H-acetate was administered ip. Samples of serum, liver, heart and carcass were obtained for analysis. Concentrations of fatty acids and cholesterol, synthesis of those and recovery of ring-labeled steroid are reported. Mortality from acute respiratory disease was very high in male rats fed beef tallow or low fat diets and very low in those fed the corn oil diet. In females, only beef tallow diet resulted in a high mortality rate, and this was lower and at a later age than in males. The most notable effects of age were in relation to fatty acid synthesis and presence of¹⁴C-acidic steroid in the carcass. In 3-month-old rats both fats depressed fatty acid synthesis in comparison to the low fat diet. At later ages beef fat ceased to depress fatty acid synthesis in both sexes. Corn oil continued to depress fatty acid synthesis up to 12 months in males and 18 months in females. The presence of¹⁴C-acidic steroid in carcass was substantial in 6-month-old rats and constituted ca. 40% of recovered¹⁴C in 18-month-old rats. The possibility that the increase in acetate incorporation into fatty acids with age in fat feeding is related to chain elongation rather than de novo synthesis is discussed. Both the presence and amount of acidic steroid in the carcass are notable and may be of importance in constructing models of cholesterol turnover. Presented in part at the AOCS Sterol Symposium, April 1970, and the Federation of American Societies for Experimental Biology, April 1971. Scientific Series Paper No. 1536, Colorado Agricultural Experiment Station.     

Inhibition by 5-(tetradecyloxy)-2-furoic acid of fatty acid and cholesterol synthesis in isolated rat hepatocytes

Fatty acid and cholesterol synthesis in isolated rat hepatocytes were strongly inhibited by 5-(tetradecyloxy)-2-furoic acid. With either³H₂O or [2-¹⁴C]acetate as the labeled precursor, the concentrations of inhibitor causing 50% decrease in fatty acid and cholesterol synthesis were, respectively, <0.005 mM and 0.020 mM. At 0.1 mM inhibitor, citrate concentration in cells from fed rats was increased by 75%; lactate and pyruvate concentrations were decreased by 30%; ethanol oxidation was decreased by 20%; with cells from starved rats, the mitochondrial [NAD⁺]/[NADH] was decreased. Other parameters were unaffected. Both its potency and its specificity indicate that 5-(tetradecyloxy)-2-furoic acid will be useful in studies on the regulation of lipid biosynthesis.     

Influence of dietary fatty acid composition on cholesterol synthesis and esterification in hamsters

To investigate the effects of dietary fat quality on synthesis and esterification of cholesterol, Syrian hamsters were fed diets containing corn, olive, coconut or menhaden oils (10% w/w) with added cholesterol (0.1% w/w). After 3 weeks, animals were sacrificed 90 min following IP injection of³H₂O. Synthesis of free cholesterol and movement of free cholesterol into ester pools were measured from³H-uptade rate in liver and duodenum. Plasma total cholesterol and triglycerides levels were highest in coconut oil-fed animals, whereas hepatic total cholesterol and ester levels were elevated in olive oil-fed animals, as compared with all other groups. No diet-related differences were seen in duodenal cholesterol or total fatty acid content. In duodenum, uptake of³H per g tissue into cholesterol was greater compared with liver; however, within each tissue,³H-uptake into cholesterol was similar across groups. Notably,³H-uptake into cholesterol ester in liver was highest in menhaden oil-fed animals. These data suggest that menhaden fish oil consumption results in enhanced movement of newly synthesized cholesterol into ester as compared with other fat types.     

Effects of ketoconazole on cholesterol synthesis and precursor concentrations in the rat liver

Ketoconazole, an antimycotic agent, given to rats for a week as 0.05% food addition had no effect on the hepatic concentrations of free and esterified cholesterol or on the activity of acyl coenzyme A: cholesterol-acyltransferase (ACAT). However, the levels of free methylated cholesterol precursors, especially lanosterols, less markedly Δ^8,24 and Δ⁸-dimethyl sterols and monomethyl sterols, were increased after only one day's treatment, while those of esterified methyl sterols were increased inconsistently, and those of free and esterified Δ⁸-lathosterol, lathosterol and desmosterol were not affected at all. Cholestyramine treatment had no significant effect on ACAT in spite of a decrease in the hepatic content of esterified cholesterol and caused a marked increase in the free cholesterol precursor levels, especially in those of lathosterols. Cholestyramine given to ketoconazole-treated rats increased the hepatic levels of Δ⁸ and Δ⁷-lathosterols but not desmosterol or methylated cholesterol precursors. Ketoconazole increased and cholestyramine markedly decreased plantssterols, sitosterol and campesterol in the liver. In serum, the contents of both lanosterols and lathosterol were increased but that of cholesterol tended to be decreased by ketoconazole (−19%). The results indicate that ketoconazole impairs demethylation processes at C-14 and to some extent at C-4 in the rat liver, resulting in lowered serum cholesterol level.     

Effects of renal factors on in vitro hepatic cholesterol synthesis in the rat

Two products derived from rat renal tissue have been shown to affect in vitro hepatic cholesterol synthesis. A premevalonate inhibitor of hepatic cholesterol synthesis is associated with the membranes of the renal endoplasmic reticulum. It is stable at −75 C and at 4 C but is heat labile. A pre-mevalonate stimulator of in vitro hepatic cholesterol synthesis is located within renal lysosomes and can be prepared in a nonsedimentable form by extraction with hypotonic buffer. While it is stable at −75 C, it loses activity at 4 C. Both of these products appear to have a molecular weight in excess of 150,000 as determined by gel filtration. Deceased.     

The effect of lidocaine onde novo phospholipid biosynthesis in the isolated hamster heart

Lidocaine is used clinically as an antiarrhythmic agent, but its effect on cardiac phospholipid metabolism has not been defined. In this study, hamster hearts were perfused with [1,3-³H]glycerol in the presence of 0.5 mg/mL lidocaine. The incorporation of radioactivities into lysophosphatidic acid, phosphatidic acid, phosphatidylethanolamine, cytidine diphosphate diacylglycerol, phosphatidylinositol, phosphatidylserine, diacylglycerol and triacylglycerol were enhanced by lidocaine treatment, whereas the labelling of phosphatidylcholine was reduced. Analyses of enzyme activities in the heart after perfusion with lidocaine revealed that the activities of phosphatidate phosphatase and acyl-coenzyme A (CoA):1,2-diacylglycerol acyltransferase were enhanced. The presence of lidocaine in the assay did not directly stimulate these enzymes. However, the activity of acyl-CoA:glycerol-3-phosphate acyltransferase was stimulated by lidocaine whereas the activity of cytidine diphosphocholine:1,2-diacylglycerol cholinephosphotransferase was inhibited by lidocaine. We conclude that lidocaine affects the regulation of phospholipid biosynthesis in the heart by both direct and indirect modulation of phospholipid biosynthetic enzymes.     

Linoleic acid-induced fatty acid changes in platelet and aorta of the rat: Effect of age and cholesterol

The influence of age and cholesterol on polyunsaturated fatty acids (PUFa) levels was studied in young and old male Sprague-Dawley rats. Animals were fed a fat-free diet supplemented with 10% (by wt) safflower oil with or without 1% cholesterol for 8 wk. As a result of cholesterol feeding, proportions of linoleic acid (18∶2n−6) and dihomo-γ-linolenic acid (30∶3n−6) were increased and and that of arachidonic acid (20∶4n−6) was decreased in the liver and platelet phospholipids in 64-wk-old rats, suggesting inhibitory effects of cholesterol on 20∶4n−6 synthesis from 18∶2n−6. The prominent age-dependent effect on the levels of PUFA was a retention of C−22 n−3 PUFA, accompanied by decreased C−22 n−6 PUFA and increased 20∶3n−6 in the liver and platelet phospholipids. Ratio of 20∶3n−6/20∶4n−6 increased in 64-wk-old rats regardless of dietary cholesterol, suggesting depressed Δ5-desaturase with age. In aorta phospholipids, 20∶3n−6 content and 20∶3n−6/20∶4n−6 ratio increased with cholesterol supplementation, but not with age. These results suggest that changes of PUFA composition of platelet phospholipids with age are closely linked with changes in liver phospholipids. The 20∶4n−6 content in both platelet and aorta phospholipids is kept constant, despite other n−6 and n−3 PUFA being affected by age.     

Refeeding varying fatty acid and cholesterol diets alters phospholipids in rat intestinal brush border membrane

Refeeding a diet initially given shortly after weaning results in a different adaptive change in the in vitro intestinal uptake of sugars and lipids than if the diet is given for the first time at a later age. This study was undertaken in rats to test the hypothesis that changes in nutrient uptake associated with refeeding diets containing beef tallow (S), beef tallow plus 1% cholesterol (Sc), fish oil (F), or fish oil plus cholesterol (Fc) are associated with changes in the brush border membrane (BBM) phospholipids and phospholipid fatty acids. Weanling Sprague-Dawley rats were fed ad libitum one of the four diets. At 35 d of age (about 2 wk after weaning), the rats were maintained on either the same diet used at weaning, or were switched to one of the other semisynthetic diets which were then fed for a further 7 wk. At week nine (2+7) the rats were either continued on the same diet or were switched back to the original diet for 2 wk (2+7+2). The groups of animals which were compared included SSSc vs. ScSSc; ScScS vs. SScS; FFFc vs. FcFFc; and FcFcF vs. FFcF. Refeeding S, Sc, F, or Fc had no effect on food consumption or on body weight gain. Refeeding Fc resulted in increased ileal BBM total phospholipids, whereas rechallenge with F resulted in a decline in the jejunal BBM ratio of phospholipid/cholesterol. Refeeding Sc resulted in a decrease in the ileal BBM phosphatidylcholine (PC). In rats rechallenged with Fc, there was increased ileal BBM sphingomyelin (SM), increased ileal BBM phosphatidylethanolamine (PE), decreased ileal BBM PC/PE, and an increased ileal BBM SM/PC. Refeeding had no effect on the fatty acyl constituents of the jejunal or ileal BBM PC or PE. These results suggest that there are late effects of the early introduction of dietary cholesterol on intestinal BBM phospholipid content and composition that may contribute to the previously reported changes in intestinal nutrient absorption.     

Relative contribution of the main tissues and organs to body fatty acid synthesis in the rat

Tritiated water was used to measure the rate of fatty acid synthesis in the main tissues and organs of 7-week old wistar male rats in order to determine the relative contribution of each tissue to body fatty acid synthesis. We reached the following conclusions: (a) the liver is the main site of fatty acid synthesis, it alone synthesizes 42% of the newly synthesized fatty acids in the body. (b) The dissectable white adipose tissues synthesize 27% of the fatty acids in the body. This group of tissues is heterogeneous because the mesenteric adipose tissue alone contains 40% of the labeled fatty acids present in the white adipose tissues. (c) Besides the intestines, organs other than the liver play a negligible role (2% of the total) in fatty acid synthesis. (d) The skin contributes 7% of the body fatty acid synthesis. (e) The rest of the carcass, essentially composed of the musculature and the skeleton, contributes 18% of body fatty acid synthesis and accounts for 33% of the extrahepatic tissue fatty acid synthesis.     

Fatty acid and cholesterol synthesis from specifically labeled leucine by isolated rat hepatocytes

Hepatocytes isolated from female rats meal-fed a high-glucose diet were incubated in Krebs-Henseleit bicarbonate medium containing 16.5 mM glucose,³H₂O, and¹⁴C-labeled amino acids (−)-Hydroxycitrate depressed the incorporation of³H₂O and [¹⁴C] alanine into fatty acids and cholesterol. Incorporation of [U-¹⁴C] leucine into lipids was not affected but incorporation of³H₂O into lipids was decreased significantly by (−)-hydroxycitrate. (−)-Hydroxycitrate depressed the incorporation of radioactivity from [2-¹⁴C]leucine into fatty acids and cholesterol by 61 and 38%, respectively, and stimulated the incorporation of radioactivity from [4,5-³H]leucine 35 and 28%. As [2-¹⁴C]leucine labels the acetyl-CoA pool and [4,5-³H]leucine labels the acetoacetate pool, it was concluded that mitochondrial 3-hydroxy-3-methylglutaryl-CoA is not incorporated intact into cholesterol, and that acetoacetate can be activated effectively in the liver cytosol for support of cholesterol and fatty acid synthesis.     

Altered fatty acid desaturation and microsomal fatty acid composition in the streptozotocin diabetic rat

Streptozotocin diabetes in the rat diminishes the synthesis of both monounsaturated and polyunsaturated fatty acids. Rat liver microsomal fatty acid composition and fatty acid desaturation were studied in the streptozotocin diabetic rat. The major alterations in fatty acid composition found in the diabetic rat were decreased proportions of palmitoleic, oleic and arachidonic acids and an increased proportion of linoleic and docosahexaeneoic acids. These findings, other than the increased docosahexaeneoic acid, probably result from the diminished liver microscomal δ9 and δ6 desaturase activities found in these animals. These changes are not due to the diminished weight gain of the diabetic animals since restricting food intake of control animals to achieve a similar weight gain failed to reproduce either the changes in fatty acid composition or the decrease in fatty acid desaturation. The increased food intake of the diabetic animal may contribute to the altered proportions of linleic and arachidonic acids since limiting food intake in diabetic animals to that of normal controls diminished the magnitude of these changes. Insulin therapy for 2 days not only reverses and overcorrects the diminished desaturase activities, but likewise reverses and overcorrects the altered fatty acid composition, with the exception of the diminished arachidonic aicd levels which are further decreased following insulin therapy. These findings strongly suggest that most of the changes in fatty acid composition in the diabetic rat are indeed caused by the diminished fatty acid desaturase activities.     

Chronic administration of eicosapentaenoic acid and docosahexaenoic acid as ethyl esters reduced plasma cholesterol and changed the fatty acid composition in rat blood and organs

Fish oils rich in n-3 fatty acids have been shown to decrease plasma lipid levels, but the underlying mechanism has not yet been elucidated. This investigation was performed in order to further clarify the effects of purified ethyl esters of eicosapentaenoic acid (EPA-EE) and docosahexaenoic acid (DHA-EE) on lipid metabolism in rats. The animals were fed EPA-EE, DHA-EE, palmitic acid, or corn oil (1 g/kg/d) by orogastric intubation along with a chow background diet for three months. At the end the animals were sacrificed. Plasma and liver lipids were measured, as well as lipid-related enzyme activities and mRNA levels. The fatty acid composition of plasma and different tissues was also determined. This study shows that, compared to the corn oil control, EPA-EE and DHA-EE lowered plasma cholesterol level, whereas only EPA-EE lowered the amount of plasma triacylglycerol. In liver peroxisomes, both EE preparations increased fatty acyl-CoA oxidase FAO activities, and neither altered 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activities. In liver microsomes, EPA-EE raised HMG-CoA reductase and acyl-CoAicholesterol acyltransferase activities, whereas DHA-EE lowered the former and did not affect the latter. Neither product altered mRNA levels for HMG-CoA reductase, low density lipoprotein-receptor, or low density lipoprotein-receptor related protein. EPA-EE lowered plasma triacylglycerol, reflecting lowered very low density lipoprotein secretion, thus the cholesterol lowering effect in EPA-EE-treated rats may be secondary to the hypotriacylglycerolemic effect. An inhibition of HMG-CoA reductase activity in DHA-EE treated rats may contribute to the hypocholesterolemic effect. The present study reports that 20∶5n-3, and not 22∶6n-3, is the fatty acid primarily responsible for the triacylglycerol lowering effect of fish oil. Finally, 20∶5n-3 was not converted to 22∶6n-3, whereas retroconversion of 22∶6n-3 to 20∶5n-3 was observed.     

Effects of the ratio of polyunsaturated and monounsaturated fatty acid to saturated fatty acid on rat plasma and liver lipid concentrations

The effects of dietary monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid+MUFA/saturated fatty acid (PUFA+MUFA/SFA) ratio on plasma and liver lipid concentrations were studied. In experiment I, when rats were fed with 40% fat (energy%, PUFA/SFA ratio 1.0) and 1% (w/w) cholesterol (C) diets for 21 d, a large amount of MUFA (28.1 energy%, PUFA+MUFA/SFA=5.7) in the diet was found to increase the plasma total C, triacylglycerol (TAG), and phospholipid (PL) as compared with the low-MUFA diet (7.0 energy%, PUFA+MUFA/SFA=1.4). The plasma very low density lipoprotein (VLDL)-C, VLDL-TAG, VLDL-PL, and low density lipoprotein (LDL)-C increased significantly in the high-MUFA diet group, but high density lipoprotein (HDL)-C did not change significantly. The high-MUFA diet resulted in greater accumulation of liver C but lesser accumulation of TAG. In experiment II, when dietary SFA was fixed at a certain level (13.2 energy%; PUFA+MUFA/SFA=2.0), rats given a larger amount of MUFA (23.1 energy%; PUFA/MUFA=0.2; MUFA/SFA=1.8) showed higher plasma and liver C levels than did the low-MUFA diet (7.7 energy%; PUFA/MUFA=2.5; MUFA/SFA=0.6). When PUFA was fixed at a certain level (24.4 energy%), there was not a significant difference in the plasma C level between the high-and low-MUFA dietary groups (PUFA+MUFA/SFA=4.8 and 8.4), but the higher PUFA+MUFA/SFA diet, which was high in MUFA/SFA ratio, significantly decreased the plasma HDL-C and TAG levels. However, when MUFA content was fixed at a certain level (16.4 energy%), no significant difference was observed between the two groups with different PUFA/SFA ratios of 0.2 and 4.1, but liver C level was raised in the higher PUFA/SFA diet. It appears that the PUFA/SFA ratio alone is unsuitable to predict the change of plasma C level, because a large amount of dietary MUFA may lead to an increase of plasma and liver lipids in rats. It seems that the prerequisites for keeping low plasma and liver C are (i) low MUFA/SFA ratio, (ii) high PUFA/MUFA ratio, and (iii) PUFA+MUFA/SFA ratio not to exceed 2.     

Cholesterol and fatty acid synthesis in swine

In incubation studies with swine tissue slices, acetate-1-¹⁴C or glucose-U-¹⁴C as substrates were incorporated more readily into fatty acids and cholesterol in adipose tissue than other tissues tested. Cholesterol and fatty acid synthesizing activity was substantial in the small intestine. When acetate was available, liver, small intestine, and adipose tissue were important sites for cholesterol synthesis. Heart and aortic tissue had marginal levels of cholesterol synthesizing ability. Lipogenesis in adult swine liver, heart, and aortic tissue was extremely low. As in tissue slices, incorporation of acetyl-1-¹⁴C CoA into fatty acids by adipose homogenates indicated high lipogenic activity. Subcellular fractionations of heart and aortic tissue indicated that the heart microsomal fraction had the highest lipogenic activity as measured by the incorporation of acetyl-1-¹⁴C CoA into fatty acids. In adult swine adipose tissue, the incorporation of glucose-U-¹⁴C into fatty acid was higher than its incorporation into glyceride-glycerol. The synthesis of glyceride-glycerol from glucose-U-¹⁴C or acetate-1-¹⁴C in liver was higher than for fatty acid synthesis. The activity of acetyl CoA carboxylase, fatty acid synthetase, citrate cleavage enzyme, nicotinamide adenine dinucleotide phosphate-malate dehydrogenase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase was considerably higher in adipose tissue than in other tissues tested, paralleling its high lipogenic capacity. A preliminary report of this paper was given at the AOCS 66th Annual Spring Meeting, Dallas, Texas, April 30, 1975, Abstr. No. 109. In partial fulfillment of the requirement for the PhD degree in Nutritional Sciences at the University of Illinois at Urbana-Champaign.     

Effects of an essential fatty acid deficiency on serum lipoproteins in the rat

Studies are reported on the effect of an essential fatty acid (EFA) deficiency in male Sprague-Dawley rats and its exacerbation by inclusion oftrans fatty acids in the diet on the level and composition of serum lipoproteins. Weanling male Sprague-Dawley rats were fed diets containing all essential nutritients and a 5% fat supplement of safflower oil (SAFF) or hydrogenated coconut oil (HCO) in 2 experiments, one for 31 wk and the other for 17 wk. For the final 3 wk of each experiment, animals were switched from each group to a 5% supplement of a concentrate of ethyl linolelaidate (TRANS). In addition, a group of animals fed the HCO diet in the first experiment were also switched to the SAFF Diet. With the development of an EFA deficiency in the HCO group, there was a decrease in the high density lipoprotein (HDL) and an increase in the very low density plus the low density (VL-LDL) lipoprotein fractions separated by heparin-manganese precipitation. Switching animals of the HCO group to the TRANS supplement exaggerated this effect and produced a very low ratio of HDL-to-VL-LDL. Analysis of the serum lipoproteins by polyacrylamide disc gel electrophoresis showed that an EFA deficiency produced a marked alternation of the HDL fraction. Changes also appeared to be produced in the VL-LDL fraction by an EFA deficiency and particularly upon switching EFA-deficient animals to the TRANS supplemented diet. Switching animals of the SAFF group to the TRANS supplement brough about an immediate reduction in HDL with a corresponding decrease in serum arachidonic acid. The data suggested a general relationship between arachidonic acid and the level and composition of HDL on the one hand, and 18∶1 and VL-LDL on the other. Accordingly, the ratio of HDL-to-VL-LDL appears to provide a sensitive biochemical index of the EFA status of the rat.