Rapid effects of the intravenous injection of a medium-chain triglyceride: fish oil emulsion on the triglyceride fatty acid pattern of soleus muscle from omega3 fatty acid-depleted rats.

Second generation rats depleted in long-chain polyunsaturated omega3 fatty acids display several features of the metabolic syndrome, including visceral obesity, liver steatosis, insulin resistance, hypertension, and cardiac hypertrophy. In the framework of an extensive study on such metabolic, hormonal and functional perturbations, the phospholipid fatty acid pattern and ex vivo metabolism of D-glucose were recently investigated in the soleus muscle of these omega3-depleted rats. The present study deals with the triglyceride fatty acid content and pattern of the soleus muscle in control animals and omega3-depleted rats. Some of the latter rats were injected intravenously 60-120 minutes before sacrifice with either an omega3 fatty acid-rich medium-chain triglyceride/fish oil emulsion (omega3-FO rats) or a control medium-chain triglyceride/olive oil emulsion (omega3-OO rats). The total fatty acid content of triglycerides was comparable in control and omega3-depleted rats and, in both cases, inversely related to their C20:4omega6 relative content. At variance with the situation found in control rats, no long-chain polyunsaturated omega3 fatty acid (C18:3omega3, C20:5omega3, C22:5omega3, C22:6omega3) was detected in the omega3-depleted rats. Unexpectedly, the triglyceride content in most long-chain polyunsaturated omega6 fatty acids (C18:2omega6, C20:3omega6, C20:4omega6 and C22:4omega6) had also decreased in the latter rats. Moreover, the activity of Delta9-desaturase was apparently increased in the omega3-depleted rats, as judged from the C16:1omega7/C16:0 and C18:1omega9/C18:0 ratios. The omega3-FO rats differed from omega3-OO rats by a lower contribution of C18:2omega6 metabolites (C18:3omega6, C20:3omega6, C20:4omega6 and C22:4omega6). These findings indicate that the prior injection of the medium-chain triglyceride/fish oil emulsion, known to increase the muscle phospholipid content in long-chain polyunsaturated omega3 fatty acids, may nevertheless accentuate the depletion in long-chain polyunsaturated omega6 fatty acids otherwise found in the triglycerides of omega3-depleted rats. Such a dual effect is reminiscent of that observed, under the same experimental conditions, for selected variables in D-glucose metabolism in the soleus muscle.     

Phospholipid fatty acid pattern and D-glucose metabolism in muscles from omega3 fatty acid-depleted rats

A depletion in long-chain polyunsaturated omega3 fatty acids may affect fuel homeostasis. In such a perspective, the present study deals mainly with the in vitro fate of D-[U-(14)C]glucose in hemidiaphragms, stretched soleus and plantaris muscle pieces obtained from normal and omega3-depleted rats (second generation) and incubated in the absence or presence of insulin. When so required, the omega3-depleted rats were injected 120 min before sacrifice with either a omega3 fatty acid-rich medium-chain triglyceride:fish oil emulsion (FO) or a control medium-chain triglyceride:olive oil emulsion (OO). The content of the soleus muscle in long-chain polyunsaturated omega3 fatty acids was severely decreased in the omega3-depleted rats, and modestly albeit significantly increased after injection of FO to these animals. In stretched soleus muscles from OO-injected omega3-depleted rats, the absolute values for glycogen synthesis measured in the absence or presence of insulin were about twice higher than in normal animals. In the OO-injected omega3-depleted rats, insulin augmented the output of (14)C-labelled amino acids, whilst such was not the case in normal animals. These and other findings suggest a lower catabolism of D-glucose relative to the anabolic process of glycogen synthesis and a lower availability of endogenous amino acids in the muscles of omega3-depleted rats, as compared to those of control animals. The prior injection of FO to the omega3-depleted rats restored a normal value for the paired ratio between the output of (14)C-labelled amino acids and acidic metabolites, but further increased glycogen net synthesis. It is proposed, therefore, that the perturbation of d-glucose metabolism in muscles from omega3-depleted rats involves a multifactorial determinism, only some of the concerned factors being susceptible to rapid correction after enrichment of cell phospholipids in long-chain polyunsaturated omega3 fatty acids.     

Preferential enrichment of liver phospholipids in docosahexaenoate relative to eicosapentaenoate in omega-3-depleted rats injected with a medium-chain triglyceride: fish oil emulsion

The bolus intravenous injection of a novel medium-chain triglyceride:fish oil (FO) emulsion was recently proposed as a tool to provoke a rapid enrichment of cell phospholipids in long-chain polyunsaturated omega-3 fatty acids. In the present study, the enrichment of liver phospholipids and triglycerides in C20:5omega-3, C22:5omega-3 and C22:6omega-3 was assessed 60min after the intravenous administration of FO (1.0ml) to second-generation omega-3-depleted rats. When compared to uninjected rats, or animals injected with a control omega-3 fatty acid-poor medium-chain triglyceride:olive oil (OO) emulsion, the enrichment of liver phospholipids, and to a lesser extent liver triglycerides, attributable to the injection of the FO emulsion was more pronounced for C22:6omega-3 than C20:5omega-3, despite the presence of equal amounts of these two omega-3 fatty acids in the injected diglycerides and triglycerides. The possible determinants and potential beneficial effects of such a difference are briefly discussed.     

Alteration of adipocyte metabolism in omega3 fatty acid-depleted rats.

Presently an insufficient supply of long-chain polyunsaturated omega3 fatty acid is prevalent in Western populations leading to potential metabolic consequences. Based on this fact, this study deals mainly with various aspects of lipid metabolism in second generation female omega3-depleted rats. The parametrial fat and body weights were higher in omega3-depleted than control animals. This coincided with liver steatosis but did not alter heart triglyceride/phospholipid ratio. The net uptake of [U-14C] palmitate by adipocytes was also higher in omega3-depleted rats than in control animals. The uptake of D-[U- 4C] glucose or [1,2 (-14)C] acetate by adipocytes was lower, however in omega3-depleted than control animals and was unaffected by insulin in the former as distinct from latter animals. Despite comparable basal lipolysis, the increase in glycerol output from adipocytes provoked by theophylline was higher in omega3-depleted than control rats. The fatty acid pattern of lipids in adipose tissue was characterized in the omega3-depleted rats by a much lower omega3 content, higher apparent Delta 9-saturase and elongase activities, lower efficiency for the conversion of C18:2omega6 to C20:4omega6 and higher efficiency for the conversion of C18:3omega3 to C20:5omega3. These features were compared to those prevailing in liver and plasma lipids. The present study thus extends knowledge on the alteration of lipid metabolism resulting from a deficiency in long-chain polyunsaturated omega3 fatty acids.     

Long-chain fatty acyl-coenzyme A-induced inhibition of glucokinase in pancreatic islets from rats depleted in long-chain polyunsaturated omega3 fatty acids

The metabolism of D-glucose was recently reported to be impaired in pancreatic islets from second generation rats depleted in long-chain polyunsaturated omega3 fatty acids. Considering the increased clearance of circulating non-esterified fatty acids prevailing in these rats, a possible inhibition of glucokinase in insulin-producing cells by endogenous long-chain fatty acyl-CoA was considered. The present study was mainly aimed at assessing the validity of the latter proposal. The activity of glucokinase in islet homogenates, as judged from the increase in D-glucose phosphorylation rate in response to a rise in the concentration of the hexose represented, in the omega3-depleted rats, was only 81.8 +/- 4.8% (n = 11; p < 0.005) of the paired value recorded in control animals. This coincided with the fact that the inclusion of D-glucose 6-phosphate (3.0 mM) and D-fructose 1-phosphate (1.0 mM) in the assay medium resulted in a lesser fractional decrease of D-glucose phosphorylation in omega3-depleted rats than in control animals. Moreover, whereas palmitoyl-CoA (50 microM) decreased the activity of glucokinase by 38.0 +/- 6.0% (n = 4; p < 0.01) in islet homogenates from normal rats, the CoA ester failed to affect significantly the activity of glucokinase in islet homogenates from omega3-depleted rats. These findings afford direct support for the view that glucokinase is indeed inhibited by endogenous long-chain fatty acyl-CoA in islets from omega3-depleted rats, such an inhibition probably participating to the alteration of D-glucose catabolism prevailing in these islets.     

Phospholipid and triacylglycerol fatty acid content and pattern in the cardiac endothelium of rats depleted in long-chain polyunsaturated omega 3 fatty acids

Rats depleted in long-chain polyunsaturated omega3 fatty acids (omega3-depleted rats) display several features of the metabolic syndrome including hypertension and cardiac hypertrophy. This coincides with alteration of the cardiac muscle phospholipid and triacylglycerol fatty acid content and/or pattern. In the present study, the latter variables were measured in the cardiac endothelium of normal and omega3-depleted rats. Samples derived from four rats each were obtained from 16 female normal fed rats and three groups of 36-40 female fed omega3-depleted rats each aged 8-9, 15-16 and 22-23 weeks. At comparable mean age, the ratio between the square root of the total fatty acid content of phospholipids and cubic root of the total fatty acid content of triacylglycerols was lower in omega3-depleted rats than in control animals. The total fatty acid content of triacylglycerols was inversely related to their relative content in C20:4omega6. Other differences between omega3-depleted rats and control animals consisted in a lower content of long-chain polyunsaturated omega3 fatty acids in both phospholipids and triacylglycerols, higher content of long-chain polyunsaturated omega6 fatty acids in phospholipids, higher activity of delta9-desaturase (C16:0/C16:1omega7 and C18:0/C18:1omega9 ratios) and elongase [(C16:0 + C16:1omega7)/(C18:0 + C18:1omega9) and C20:4omega6/C22:4omega6 ratios], but impaired generation of C22:6omega3 from C22:5omega3 in the former rats. These findings support the view that cardiovascular perturbations previously documented in the omega3-depleted rats may involve impaired heart endothelial function.     

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.     

Pancreatic islet function in omega-3 fatty acid-depleted rats: alteration of calcium fluxes and calcium-dependent insulin release

Considering the insufficient supply of long-chain polyunsaturated omega-3 fatty acids often prevailing in Western populations, this report deals mainly with alterations of Ca(2+) fluxes and Ca(2+)-dependent insulin secretory events in isolated pancreatic islets from omega-3-depleted rats. In terms of (45)Ca(2+) handling, the islets from omega-3-depleted rats, compared with those from normal animals, displayed an unaltered responsiveness to an increase in extracellular K(+) concentration, a lower inflow rate and lower fractional outflow rate of the divalent cation, and higher (45)Ca(2+)-labeled cellular pool(s) at isotopic equilibrium. The latter anomaly was corrected 120 min after intravenous injection of a novel medium-chain triglyceride-fish oil (MCT:FO) emulsion, distinct from a control omega-3-poor MCT-olive oil (MCT:OO) emulsion. At 8.3 mM D-glucose, insulin release was higher in islets from omega-3-depleted rats vs. control animals, coinciding with a higher cytosolic Ca(2+) concentration. The relative magnitude of the increase in insulin output attributable to a rise in D-glucose as well as extracellular Ca(2+) or K(+) concentration, to the absence vs. presence of verapamil and to the presence vs. absence of extracellular Ca(2+), theophylline, phorbol 12-myristate 13-acetate, or Ba(2+), was always more pronounced in islets from omega-3-depleted rats injected with the MCT:OO compared with the MCT:FO emulsion. A comparable situation prevailed when comparing islets from noninjected omega-3-depleted and normal rats. In light of these and previous findings, we propose that an impairment of Na(+),K(+)-ATPase activity plays a major, although not an exclusive, role in the perturbation of Ca(2+) fluxes and Ca(2+)-dependent secretory events in the islets from omega-3-depleted rats.     

L-glutamine and palmitate catabolism in pancreatic islets from rats depleted in long-chain polyunsaturated omega 3 fatty acids

The catabolism of D-glucose was recently found to be impaired in pancreatic islets from rats depleted in long-chain polyunsaturated omega3 fatty acids. The specificity of this alteration was now investigated by characterizing the oxidative fate of endogenous nutrients in islets preincubated with either L-[U-14C]glutamine or [U-14C]palmitate and then incubated variously in the absence of D-glucose, presence of the hexose or presence of metabolic poisons. Relative to their radioactive content after preincubation, the production of 14CO2 by islets prelabelled with [U-14C]glutamine was higher in omega3-depleted rats than control animals. The enhancing action of D-glucose upon such production was impaired, however, in the omega3-depleted rats. The net uptake of 14C-palmitate and absolute value for 14CO2 output were both increased in omega3-depleted rats, whilst the ratio between 14CO2 output and islet radioactive content was decreased in the same animals. The inhibition of 14CO2 production by metabolic poisons was comparable in all cases. These results are consistent with recent findings on such items as the availability of endogenous amino acids and uptake of unesterified fatty acids in extrapancreatic sites of the omega3-depleted rats. They also support the view that the alteration of D-glucose metabolism in the islets of the latter animals may be attributable, in part at least, to alteration of glucokinase kinetics by high intracellular acyl-CoA levels.     

Augmentation of unesterified arachidonic acid in the renal inner medulla of dexamethasone-treated rats. Relationship to altered triglyceride metabolism

The present study was designed to investigate the effect of dexamethasone treatment for 2 weeks (2.5 mg/kg/week, subcutaneously) on the level of unesterified fatty acids, particularly arachidonic acid, in the renal medulla of rats, and to relate the observed effect to changes in the tissue concentration and the fatty acid composition of renal medulla phospholipids and triglycerides. Dexamethasone treatment caused an increase in the renal inner medulla level of unesterified fatty acids, including arachidonic acid, that was associated with a reduction of triglycerides and of arachidonic acid esterified into triglycerides, and with an increase in the rate of fatty acids esterification into triglycerides. In contrast, dexamethasone treatment did not affect the renal medulla concentration of phospholipids, the arachidonic acid content of renal medulla phospholipids, or the rate of esterification of fatty acids into renal medulla phospholipids. In the face of increased fatty acid esterification into triglycerides, the finding of reduced triglyceride levels in the renal medulla of dexamethasone-treated rats suggests excessive triglyceride breakdown. If so, fatty acids including arachidonic acid liberated from triglycerides may contribute to elevation of unesterified fatty acid levels in the renal medulla during dexamethasone treatment. The increased level of free arachidonic acid in the renal medulla of dexamethasone-treated rats may explain in part the reported effect of this steroid in increasing urinary prostaglandins.     

Age‐Related Changes in Fatty Acids in Obese Offspring of Streptozotocin‐Induced Diabetic Rats

Objective: The long‐term effects of fetal hyperinsulinemia, time course of changes in liver and very‐low‐density lipoprotein (VLDL) lipid levels and fatty acid compositions were investigated in obese offspring of streptozotocin‐induced mildly diabetic rats. Research Methods and Procedures: Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin on day 5 of gestation. Control pregnant rats were injected with citrate buffer. Liver and VLDL lipids and fatty acids were analyzed in offspring at different ages. Results: At birth, obese pups had higher VLDL triglyceride levels, saturated fatty acids, and C20:4n‐6. They also had lower C18:2n‐6 proportions in VLDL triglycerides, phospholipids, and cholesteryl esters than controls pups. In 1‐month‐old male and female obese rats, VLDL and liver lipid amounts were similar to those in their respective controls; however, high levels of C18:2n‐6 and C20:4n‐6 were noted in liver and VLDL lipids. At the age of 2 months, liver and VLDL triglyceride levels were higher in obese females than in control females. Fatty acid abnormalities seen in obese rats included low C18:3n‐3 and high C22:6n‐3 proportions in liver triglycerides and phospholipids. At the age of 3 months, obese rats, both males and females, compared with control animals, had higher VLDL and hepatic lipids with reduced C20:4n‐6 levels and polyunsaturated/saturated fatty acids ratios in hepatic and VLDL triglycerides and phospholipids. Discussion: Fetal obesity, associated with alterations in VLDL lipid fatty acid composition, represents an important risk factor for adult obesity and diabetes.     

Gastric lipolysis of milk lipids in suckling rats

Fatty acid composition of the major lipid classes in stomach contents of suckling rats at 1, 5, 10, 17 and 20 days of lactation was compared to that of milk lipids. In milk, 98% of fatty acids were in triacylglycerols at all lactation times. Medium-chain fatty acid concentrations increased from 8% in colostrum to 26% at day 5. Fatty acid composition of stomach acylglycerols at all lactation times was different from that of milk triacylglycerols, containing less medium-chain fatty acids, 8:0 and 10:0. This preferential hydrolysis was also shown by higher concentrations of medium-chain fatty acids in the free fatty acid fraction. The lipolysis of medium-chain fatty acids from triacylglycerols resulted in the appearance of di- and monoacylglycerols with 50-100% higher amounts of 14:0 and 16:0. The similar fatty acid composition of products suggests that considerable lipolysis occurred in stomachs of suckling rats even at 1 day of age. Although there was a 10-fold increase in milk consumption, the extent of lipolysis was similar throughout the suckling period because of a parallel rise in lingual lipase levels.     

Genesis of fatty liver and hyperlipemia in the fetal guinea pig.

10 to 20% of [1-14C] palmitate injected into pregnant guinea pigs was recovered in lipids of their fetuses. From these data and the rate of transport of palmitate in maternal blood, it appears that placental transport of free fatty acids can account for the accumulation of lipids in late gestational fetuses. About 80% of the labeled palmitate in the fetus appeared initially in lipids of the liver. 14C appeared in plasma triglyceride fatty acids after a few minutes and subsequently accumulated in lipids of white and brown adipose tissue, suggesting that much of the palmitate deposited in adipose tissue were derived from hepatogenous triglyceride fatty acids. By contrast, 14C was usually maximal in heart and carcass lipids before it appeared in plasma triglyceride fatty acids. Lipoprotein lipase activity in fetal adipose tissue was low, and activity of cofactor protein of lipoprotein lipase in fetal blood plasma was much lower than that observed in other mammalian species. On the basis of these and earlier observations, it is concluded that the accumulation of triglycerides in liver and blood plasma of fetal guinea pigs during late gestation is at least partly the result of the large uptake of maternally derived free fatty acids by the fetal liver accompanied by rapid synthesis and secretion of triglyceride-rich very low density lipoproteins into the blood. However, limited uptake of triglyceride fatty acids in adipose tissue may contribute to the fatty liver and hyperlipemia.     

Selective incorporation of polyunsaturated fatty acids of the omega-3 family in the diet into the cerebellar phospholipids of rats

TLC, GLC and GC-MS methods were applied for studying the fatty acid composition of rat cerebellum phospholipids. 75 male Wistar rats had a diet without fat for 6 weeks and then a diet with linseed oil, fish oil in combination with lard and mixture of sunflower oil with lard (control group) for 3 months; PUFA omega 6/omega 3 rations were 0.27; 0.5 and 45.0. PUFA omega 3 in all fractions were represented mainly by 22:6 omega 3 (0.2-12.0%) acid and its share depends on the total PUFA omega 3 amount in the diet. The absence of 18:3, 20:5 and 22:5 omega 3 in cerebellum lipids, fed in great amount with test diets, suggested that these acids are rapidly desaturated and elongated to 22:6 omega 3 at the blood-brain barrier. Established competitive inhibition of desaturases responsible for the synthesis of tissues PUFA omega 6 and omega 3 proves the expressed regulatory effect of alimentary factor on brain lipids.     

Fatty liver produced by dietary deficiencies: its pathogenesis and potentiation by ethanol

In a study of the pathogenesis of hepatic fat accumulation under experimental conditions mimicking chronic alcoholism, rats were fed a low-fat diet, deficient in amino acids and choline, containing either ethanol or isocaloric amounts of carbohydrate. Dietary deficiencies alone produced a moderately fatty liver after 24 days. The combination of ethanol and dietary deficiencies resulted in enhanced lipid accumulation, which was apparent after only 11 days. In an investigation of the origin of hepatic triglyceride fatty acids, the experiment was repeated after the adipose lipids had been marked by the feeding of oils containing characteristic fatty acids (linseed oil, containing linolenate, or coconut oil, containing laurate and myristate). In all animals, the fatty acid composition of the hepatic triglycerides differed markedly from that of adipose tissue; it had a larger percentage of endogenously synthesized fatty acids and a five times smaller percentage of the marker fatty acids. In addition, ethanol feeding resulted in a greater retention of the marker fatty acids in the adipose tissue. Thus, the deposition of hepatic triglycerides produced by the feeding of deficient diets is markedly potentiated by ethanol; the triglyceride fatty acids accumulated under these conditions appear to originate, for the most part, not from mobilization of depot fat, but from endogenous synthesis.     

Metabolism of chylomicrons by the isolated rat liver

Isolated livers perfused with washed corn oil chylomicrons labeled in vivo with palmitic acid-1-(14)C removed a large proportion of the chylomicrons. Slices from these livers oxidized chylomicron fatty acid esters to both carbon dioxide and acetoacetate. The liver slices also generated free fatty acids from chylomicron lipids and converted chylomicron triglycerides to phospholipids. Similar activities were observed in rat liver slices prepared shortly after the intravenous administration of chylomicrons to intact rats. The observed chylomicron uptake and lipid conversions were similar in livers from both fed and fasted rats. Fasting increased the oxidation of chylomicron fatty acid esters by livers labeled in vivo and by perfusion. In livers removed from intact rats given labeled chylomicrons, the triglyceride-(14)C to phospholipid-(14)C ratio was high, a finding unexpected if the liver had acquired this (14)C by removal of circulating fatty acids formed by extrahepatic lipolysis. These results demonstrate the ability of the liver to remove and utilize chylomicrons directly and suggest that direct removal accounts for a significant portion of the chylomicron fatty acids utilized by the liver of intact rats.     

Effect of essential fatty acid deficiency on release of triglycerides by the perfused rat liver

Studies are reported on release of triglycerides during perfusion of livers of male Sprague-Dawley rats fed a fat-free diet or diets containing hydrogenated coconut oil or corn oil. Perfusions were carried out with Krebs-Ringer bicarbonate buffer containing albumin with and without infusion of oleate or linoleate. Infusion with sodium oleate or linoleate caused an accumulation of triglycerides in the livers of the corn oil-fed animals and stimulated the release of triglycerides into the perfusing medium. In similar experiments with essential fatty acid-deficient animals, which were fed fat-free diets or diets containing hydrogenated coconut oil, there was no increase in secretion of triglycerides into the perfusate, and the amount of triglyceride which accumulated in the liver was greater than in the livers of the control (corn oil-fed) animals. Tracer experiments with oleate-1-(14)C or linoleate-1-(14)C also showed that with livers of essential fatty acid-deficient animals, secretion of triglyceride into the perfusate was not stimulated by infusion of fatty acids into the perfusing medium. It is concluded that impairment of the secretion of triglycerides is a factor in the accumulation of fat in the livers of essential fatty acid-deficient animals.     

Quantitative analysis of metabolism of hepatic triglyceride in ethanol-treated rats.

An acute intraperitoneal injection of ethanol (0.7 or 2.1g/kg body wt.) causes the reversible, dose-dependent accumulation of hepatic triglyceride in rats. By using a pulse of [14C]palmitate injected into a tail vein, it was found that ethanol (2.1g/kg)had no effect on the flux of unesterified fatty acid of serum (4.3mumol/min per 100g body wt.). However, either dose increased the fraction of the total flux going to liver from 0.16 to0.27 as rapidly as could be measured (30s), and it remained elevated until all ethanol had been cleared from the blood. The fraction of the total radioactivity in lipids of liver that was in triglyceride increased linearly for 1 h from 30 to 50% and there was a simultaneous decrease in phospholipid from 60 to 40%. The rate of synthesis of hepatic triglyceride derived directly from unesterified fatty acid of serum was calculated by using the flux rate of unesterified fatty acid in serum, the fractional hepatic uptake of this flux, and the percentage of liver fatty acid esterified to triglyceride. This contribution is related to the total synthetic rate of hepatic triglyceride (rate of accumulation+rate of release) to determine quantitatively how much of the developing fatty liver is attributable to increased uptake of unesterfied fatty acid of serum. At the higher dose of ethanol, about half of the accumulating triglyceride is derived from this source, whereas with the lower dose of ethanol it can account for all of the build-up.     

Validation of a procedure for exogenous isotopic labeling of lipoprotein triglyceride with radioactive triolein.

A procedure has been developed for the exogenous isotopic labeling of triglyceride-rich lipoproteins (chylomicrons and very low density lipoproteins) using high specific activity radioactive triglyceride in the presence of aqueous dimethyl sulfoxide. The labeled product lipoproteins showed unchanged chemical and physical properties. When the particles had also been labeled biologically by incorporation of unesterified fatty acids into the triglycerides of lipoproteins secreted by liver or intestine, both endogenous and exogenous labels were removed at the same rates in the isolated perfused heart and liver or in intact or functionally hepatectomized rats. These experiments additonally indicated that the triglyceride fatty acid composition of chylomicrons and very low density lipoproteins was unchanged during triglyceride depletion in the peripheral tissues. Using such labeled lipoproteins it has been shown that uptake of remnant lipoprotein cholesteryl ester and triglyceride by the liver is simultaneous. The labeling procedure described should prove suitable for kinetic studies of the disposition of the various lipoprotein non-polar ('core') lipids.     

Content of prostaglandin biosynthesis precursors in the kidney lipids in the development of spontaneous arterial hypertension

The content of linoleic (18 : 2 omega 6), arachidonic; (20 : 4 omega 6) and eicosatrienic (20 : 3 omega 9) acids was studied and compared in lipids of the renal cortex and papilla of spontaneously hypertensive Okamoto-Aoki rats (SHR) and normotensive Wistar rats (NR) aged 10 days, 1, 2 and 4 months. The level of 18 : 2 omega 6 in lipids of the renal cortex and papilla of SHR was lower at the prehypertensive stage (10 days) and at the stage of persistent hypertension as compared to that seen in NR. The content of 20 : 4 omega 6 in phospholipids and triglycerides of the cortex and in phospholipids of the papilla of SHR did not differ from that in NR. In triglycerides of the papilla of SHR of all age groups, the content of 20 : 4 omega 6 was higher than in NR. In phospholipids of SHR cortex, the content of 20 : 3 omega 9 was higher than that in NR. As for lipids of the papilla, 20 : 3 omega 9 was not detectable either in NR or SHR. It is concluded that the data obtained are of interest for the characteristics of the renal prostaglandin system in SHR.