Plasma Unesterified Fatty Acids Research Articles

Plasma Lipolysis and Changes in Plasma and Cerebrospinal Fluid Signaling Lipids Reveal Abnormal Lipid Metabolism in Chronic Migraine.

BackgroundLipids are a primary storage form of energy and the source of inflammatory and pain signaling molecules, yet knowledge of their importance in chronic migraine (CM) pathology is incomplete. We aim to determine if plasma and cerebrospinal fluid (CSF) lipid metabolism are associated with CM pathology.MethodsWe obtained plasma and CSF from healthy controls (CT, n = 10) or CM subjects (n = 15) diagnosed using the International Headache Society criteria. We measured unesterified fatty acid (UFA) and esterified fatty acids (EFAs) using gas chromatography-mass spectrometry. Glycerophospholipids (GP) and sphingolipid (SP) levels were determined using LC-MS/MS, and phospholipase A2 (PLA2) activity was determined using fluorescent substrates.ResultsUnesterified fatty acid levels were significantly higher in CM plasma but not in CSF. Unesterified levels of five saturated fatty acids (SAFAs), eight monounsaturated fatty acids (MUFAs), five ω-3 polyunsaturated fatty acids (PUFAs), and five ω-6 PUFAs are higher in CM plasma. Esterified levels of three SAFAs, eight MUFAs, five ω-3 PUFAs, and three ω-6 PUFAs, are higher in CM plasma. The ratios C20:4n-6/homo-γ-C20:3n-6 representative of delta-5-desaturases (D5D) and the elongase ratio are lower in esterified and unesterified CM plasma, respectively. In the CSF, the esterified D5D index is lower in CM. While PLA2 activity was similar, the plasma UFA to EFA ratio is higher in CM. Of all plasma GP/SPs detected, only ceramide levels are lower (p = 0.0003) in CM (0.26 ± 0.07%) compared to CT (0.48 ± 0.06%). The GP/SP proportion of platelet-activating factor (PAF) is significantly lower in CM CSF.ConclusionsPlasma and CSF lipid changes are consistent with abnormal lipid metabolism in CM. Since plasma UFAs correspond to diet or adipose tissue levels, higher plasma fatty acids and UFA/EFA ratios suggest enhanced adipose lipolysis in CM. Differences in plasma and CSF desaturases and elongases suggest altered lipid metabolism in CM. A lower plasma ceramide level suggests reduced de novo synthesis or reduced sphingomyelin hydrolysis. Changes in CSF PAF suggest differences in brain lipid signaling pathways in CM. Together, this pilot study shows lipid metabolic abnormality in CM corresponding to altered energy homeostasis. We propose that controlling plasma lipolysis, desaturases, elongases, and lipid signaling pathways may relieve CM symptoms.

Plasma Unesterified Fatty-Acid Profile Is Dramatically and Acutely Changed under Ischemic Stroke in the Mouse Model.

Although plasma biomarkers would facilitate rapid and accurate diagnosis of ischemic stroke for immediate treatment, no such biomarkers have been developed to date. In the present study, we tested our hypothesis that plasma unesterified fatty acids (FFA) are altered at early stages of acute ischemic stroke. Plasma was collected from mice 2 h after the permanent middle cerebral artery occlusion (pMCAo) onset, as well as from sham operated and control animals. After 2 h, pMCAo significantly changed the plasma FFA profile with the most dramatic 2- to 3-fold relative increase in very long n-3 and n-6 FFA including 20:4n-6, 22:4n-6, 22:5n-6, and 22:6n-3. Changes in the plasma FFA profile are consistent with FFA liberation from brain phospholipid hydrolyzed under ischemic insult. These results identify, for the first time, the plasma FFA profile as a potential biomarker for an early ischemic stroke within the therapeutic window for thrombolytic treatment. Further studies are required to confirm its specificity and sensitivity in clinical settings.

Accelerated Clearance of Plasma Triglycerides and Free Fatty Acids in ω3-depleted Rats

The present study aims mainly at exploring the effects of a severe depletion in polyunsaturated long-chain omega3 fatty acids upon the fate of circulating lipids. The plasma concentration and fatty acid pattern of triglycerides, diglycerides, free fatty acids, and phospholipids were measured in omega3-depleted and control rats injected intravenously one hour before sacrifice with either saline, a control medium-chain triglyceride:olive oil emulsion or a medium-chain triglyceride:fish oil emulsion recently found to rapidly increase the phospholipid content of C20:5omega3 and C22:6omega3 in different cell types. The estimated fractional removal rate of the injected triglycerides and the clearance of free fatty acids from circulation were both higher in omega3-depleted rats than in control animals. The injection of the lipid emulsions apparently inhibited intracellular lipolysis, this being least pronounced in omega3-depleted rats. The increased clearance of circulating triglycerides and unesterified fatty acids in omega3-depleted rats may favor the cellular accumulation of lipids. In turn, such an accumulation and the lesser regulatory inhibition of tissular lipolysis may match the increased clearance of circulating unesterified fatty acids and, hence, account for the lack of any significant difference in plasma unesterified fatty acid concentration between these and control animals.

Upregulated liver conversion of α-linolenic acid to docosahexaenoic acid in rats on a 15 week n-3 PUFA-deficient diet

We quantified incorporation rates of plasma-derived alpha-linolenic acid (alpha-LNA, 18:3n-3) into "stable" liver lipids and the conversion rate of alpha-LNA to docosahexaenoic acid (DHA, 22:6n-3) in male rats fed, after weaning, an n-3 PUFA-adequate diet (4.6% alpha-LNA, no DHA) or an n-3 PUFA-deficient diet (0.2% alpha-LNA, no DHA) for 15 weeks. Unanesthetized rats were infused intravenously with [1-14C]alpha-LNA, and arterial plasma was sampled until the liver was microwaved at 5 min. Unlabeled alpha-LNA and DHA concentrations in arterial plasma and liver were reduced >90% by deprivation, whereas unlabeled arachidonic acid (20:4n-6) and docosapentaenoic acid (22:5n-6) concentrations were increased. Deprivation did not change alpha-LNA incorporation coefficients into stable liver lipids but increased synthesis-incorporation coefficients of DHA from alpha-LNA by 6.6-, 8.4-, and 2.3-fold in triacylglycerol, phospholipid, and cholesteryl ester, respectively. Assuming that synthesized-incorporated DHA eventually would be secreted within lipoproteins, calculated liver DHA secretion rates equaled 2.19 and 0.82 micromol/day in the n-3 PUFA-adequate and -deprived rats, respectively. These rates exceed the published rates of brain DHA consumption by 6- and 10-fold, respectively, and should be sufficient to maintain normal and reduced brain DHA concentrations, respectively, in the two dietary conditions.

Selective remodeling of cardiolipin fatty acids in the aged rat heart

BackgroundThe heart is rich in cardiolipin, a phospholipid acylated in four sites, predominately with linoleic acid. Whether or not aging alters the composition of cardiolipin acyl chains is controversial. We therefore measured the fatty acid concentration of cardiolipin in hearts of 4, 12 and 24 month old rats that consumed one diet, adequate in fatty acids for the duration of their life.ResultsThe concentration (nmol/g) of linoleic acid was decreased in 24 month old rats (3965 ± 617, mean ± SD) vs 4 month old rats (5525 ± 656), while the concentrations of arachidonic and docosahexaenoic acid were increased in 24 month old rats (79 ± 9 vs 178 ± 27 and 104 ± 16 vs 307 ± 68 for arachidonic and docosahexaenoic acids, 4 months vs 24 months, respectively). Similar changes were not observed in ethanolamine glycerophospholipids or plasma unesterified fatty acids, suggesting specificity of these effects to cardiolipin.ConclusionThese results demonstrate that cardiolipin remodeling occurs with aging, specifically an increase in highly unsaturated fatty acids.

Pancreatic Islet Function in ω3 Fatty Acid-Depleted Rats: Glucose Metabolism and Nutrient-Stimulated Insulin Release

In order to gain information on the determinism of the perturbation of fuel homeostasis in situations characterized by a depletion in long-chain polyunsaturated omega3 fatty acids (omega3), the metabolic and hormonal status of omega3-depleted rats (second generation) was examined. When required, these rats were injected intravenously 120 min before sacrifice with a novel medium-chain triglyceride-fish oil emulsion able to provoke a rapid and sustained increase of the omega3 content in cell phospholipids. The measurement of plasma glucose, insulin, phospholipid, triglyceride, and unesterified fatty acid concentration indicated modest insulin resistance in the omega3-depleted rats. The plasma triglyceride and phospholipid concentrations were decreased in the omega3-depleted rats with abnormally low contribution of omega3 in both circulating and pancreatic islet lipids. The protein, insulin, and lipid content of the islets, as well as their intracellular and extracellular spaces, were little affected in the omega3-depleted rats. The metabolism of D-glucose in the islets of omega3-depleted rats was characterized by a lesser increase in D-[5-3H]glucose utilization and D-[U-14C]glucose oxidation in response to a given rise in hexose concentration and an abnormally low ratio between D-glucose oxidation and utilization. These abnormalities could be linked to an increased metabolism of endogenous fatty acids with resulting alteration of glucokinase kinetics. The release of insulin evoked by D-glucose, at a close-to-physiological concentration (8.3 mM), was increased in the omega3-depleted rats, this being considered as consistent with their insulin resistance. Relative to such a release, that evoked by a further rise in D-glucose concentration or by non-glucidic nutrients was abnormally high in omega3-depleted rats, and restored to a normal level after of the intravenous injection of the omega3-rich medium-chain triglyceride-fish oil emulsion. Because the latter procedure failed to correct the perturbation of D-glucose metabolism in the islets of omega3-depleted rats, it is proposed that the anomalies in the secretory behaviour of islets in terms of their response to an increase in hexose concentration or non-nutrient secretagogues is mainly attributable to alteration in K+ and Ca2+ handling, as indeed recently documented in separate experiments.

The effect of a linseed oil diet on hibernation in yellow-bellied marmots ( Marmota flaviventris)

The essential fatty acids (EFAs), α-linolenic acid (18:3,n-3) and linoleic acid (18:2,n-6) are known to be important for mammalian hibernation. In marmots ( Marmota flaviventris), reducing both dietary EFAs alters hibernation patterns by causing an increase in energy expenditure, but hibernation still occurs. In this study, marmots fed a diet high in α-linolenic acid, with normal linoleic acid levels, had significantly ( p < 0.05) more α-18:3 in their WAT and plasma unesterified fatty acids after 4 months than did marmots fed a control diet. During the winter, the control marmots hibernated normally while the marmots fed the α-18:3 diet did not hibernate, continued to eat, and lost less mass than the control group during the winter. These results suggest that α-18:3 may play a role in regulating normal hibernation behavior in marmots.

Postprandial decrease in plasma unesterified fatty acids during n−3 fatty acid feeding is not caused by accumulation of fatty acids in adipose tissue

Dietary supplementation of very long-chain n−3 fatty acids to rats reduces postprandial plasma concentrations of triacylglycerol, unesterified fatty acids and glycerol after long-term feeding by unknown mechanisms [Rustan et al., J. Lipid Res. 34 (1993) 1299–1309]. In the present study we examine the role of adipose tissues in metabolism of fatty acids. Postprandial plasma concentrations of triacylglycerol, unesterified fatty acids and glycerol were reduced by 75%, 50% and 30%, respectively, during 49 days of feeding high-fat diets containing n−3 fatty acids (6.5% n−3 fatty acid concentrate, 13% lard) as compared to lard (19.5% lard). These differences were observed already after two days of feeding. Plasma concentration of unesterified very long-chain n−3 fatty acids increased to 50 μM in n−3 fatty acid-supplemented rats, whereas these fatty acids were undetectable in lard-fed animals. The n−3 fatty acid-enriched diet limited cell volumes of perirenal and epididymal adipocytes by 40% and 30%, respectively, after 49 days, as compared to lard feeding. This reduction in cell volume was not due to reduced synthesis of glycerolipids in epididymal adipocytes. Acute incubation of perirenal and epididymal adipocytes with oleic acid or eicosapentaenoic acid, caused similar increase in synthesis of triacylglycerol. Dietary supplementation with n−3 fatty acids decreased basal and total lipolysis (isoprenalin-stimulated) in perirenal adipocytes. Basal lipolysis in epididymal adipocytes was reduced by n−3 fatty acids only after 49 days. n−3 fatty acids increased total lipolysis in mesenteric and subcutaneous fat cells compared to adipocytes derived from lard-fed animals, whereas basal lipolysis was unchanged. These results suggest that the reduced postprandial plasma concentration of unesterified fatty acids after n−3 fatty acid-supplementation is not caused by accumulation of fatty acids in adipose tissue. The reduced trophic growth of adipocytes might be due to decreased supply of unesterified fatty acids for triacylglycerol storage.

Very Low Activated Factor VII and Reduced Factor VII Antigen in Familial Abetalipoproteinaemia

Abetalipoproteinaemia is a rare disorder of apolipoprotein B metabolism associated with extremely low plasma concentrations of triglyceride. To discover whether the general positive association between factor VII and triglyceride levels extends to this condition, 5 patients were compared with 18 controls. All patients had a triglyceride below 100 micromol/l. Plasma unesterified fatty acid concentration was normal. Although factor IX activity was only slightly reduced (mean 88% standard) and factor IX antigen was normal, mean activated factor VII in patients was strikingly reduced to 34% of that in controls, a level similar to that found in haemophilia B. The patients' mean factor VII activity and factor VII antigen were also significantly reduced to 54% and 63% of those in controls, respectively. Mean factor XI activity and tissue factor pathway inhibitor activity were reduced in patients to 70% and 75% of control values respectively, while factor XII, factor XI antigen, factor X, prothrombin and protein C were normal.

Relationships Among Plasma Aldosterone, High-Density Lipoprotein Cholesterol, and Insulin in Humans

To investigate the pathogenesis of hypertension in patients with obesity and insulin resistance and to explore the role of plasma lipids, we studied 30 subjects at the end of 7 days of low (20 mEq/d) then high (200 mEq/d) sodium diets. Glucose and insulin tolerance tests were performed at the end of each week and blood and urine collected for measurements of plasma aldosterone, renin activity, electrolytes, insulin, and lipoproteins. There was a strong negative correlation between plasma aldosterone and high-density lipoprotein cholesterol during both diets. There were weaker positive correlations between plasma aldosterone and insulin or triglycerides. When the aldosterone-renin ratio was the dependent variable and the correlation controlled for serum potassium, the inverse relationship with high-density lipoprotein cholesterol and the positive correlation with insulin remained, but only during the high salt diet. Subjects were divided into three groups based on high-density lipoprotein cholesterol. Subjects with the lowest high-density lipoprotein cholesterol levels showed the highest aldosterone, plasma triglycerides, body mass index, and waist-to-hip ratio. Those subjects also demonstrated the greatest resistance to insulin action on glucose and plasma unesterified fatty acids. There was a weak direct correlation between plasma aldosterone and systolic blood pressure during the high salt diet. These data suggest that high aldosterone levels may be a link between dyslipidemia, insulin resistance, and hypertension, a relationship made more evident by high salt intake.

Lipolysis of triglyceride-rich lipoproteins activates coagulant factor XII: A study in familial lipoprotein-lipase deficiency

A high factor VII coagulant activity (VII c), a marker of increased risk of coronary heart disease, is frequently found in types IIb and IV hyperlipidaemia, but its cause is not fully understood. Factor VII can be activated by factor XII a, generated from factor XII upon activation of the contact system of coagulation. Ten patients with familial lipoprotein-lipase (LPL) deficiency and 10 healthy control subjects were therefore compared to explore the hypothesis that high concentrations of unesterified fatty acids (UFA), released from triglyceride-rich lipoproteins by LPL, are a source of factor XII activation and hence the increased VII c that is observed post-prandially and in non-LPL-deficient hypertriglyceridaemic states. Mean plasma cholesterol and triglyceride concentrations were, respectively, 1.5- and 19-fold higher in the patients than controls, due to increases in very-low-density lipoproteins and chylomicrons. The concentration and composition of plasma UFA were similar in both groups. In conformity with the hypothesis, VII c was not increased in the LPL-deficient group, despite their massive hypertriglyceridaemia. Furthermore, when the patients' plasma was treated with LPL, factor XII was activated promptly and substantially, whereas no similar effect was observed in the controls. These results suggest that high concentrations of circulating triglyceride-rich lipoproteins will increase VIII in the presence of LPL.

Salt loads raise plasma fatty acids and lower insulin.

Some fatty acids are potent inhibitors of angiotensin binding and aldosterone production in adrenal glomerulosa cells and thereby may be involved in regulating salt and water balance. To study the possible regulation of fatty acids by salt, we measured the levels of unesterified fatty acids in plasma from patients subjected to extremes of dietary salt intake and saline infusion. Insulin and catecholamines, two known regulators of plasma fatty acids, also were measured. Infusion of 2 l saline over 4 hours caused the levels of most unesterified fatty acids to rise. Total unesterified fatty acids rose 60-100%. A high salt diet caused a smaller rise in total unesterified fatty acids (approximately 33%). In both instances, oleic and palmitoleic acids showed the greatest proportionate increases, whereas stearic acid was relatively unaffected. When salt loads were administered by either intravenous or dietary routes, plasma insulin levels fell by approximately 50%. Plasma norepinephrine increased after saline infusion but not during a high salt diet. Postsaline levels of fatty acids correlated inversely with postsaline levels of aldosterone, supporting a possible role for fatty acids as physiological regulators of the adrenal glomerulosa. A rise in plasma fatty acids and fall in insulin in response to salt loads could act in concert to increase sodium excretion, constituting a physiological mechanism contributing to salt and water balance.

Short Tertatolol Treatment Does not Impair the Hormone and Metabolic Responses to Exercise and Hypoglycemia in Diabetics

Beta-blockers can precipitate hypoglycemia and mask its warning signs. Ten male insulin-dependent, otherwise healthy diabetic patients underwent two submaximal exercise tests and two insulin-induced hypoglycemic events (0.2 u/Kg short-acting insulin IV) after six days administration of placebo followed by tertatolol, a non selective beta-blocker (5 mg once daily). Tertatolol modified neither the exercise-induced changes in blood glucose, lactate and plasma unesterified fatty acid levels, nor those of counter regulatory hormones (glucagon, growth hormone, cortisol), while blood pressure, heart rate and plasma renin activity were significantly reduced, proving that tertatolol had actually been ingested, and was active. During the insulin-induced hypoglycemia, similarly tertatolol did not modify the course of the plasma fuels and hormones. Particularly, hypoglycemia was neither deeper nor more prolonged in the presence than in the absence of tertatolol. Warning symptoms were not affected except for palpitations which were not perceived. These results suggest that tertatolol did not precipitate hypoglycemia following exercise, and did not aggravate insulin-induced hypoglycemia in short term administration, and in otherwise healthy diabetic patients.

Effects of conditioned running on plasma, liver and brain tryptophan and on brain 5‐hydroxytryptamine metabolism of the rat

An investigation was made into the effects of conditioned running (1 h and 2 h at 20 m min-1), which accelerates lipolysis, on the concentrations of tryptophan (Trp) in plasma, liver and brain and on 5-hydroxytrptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in brain. Running caused time-dependent increases in plasma free Trp and brain Trp of the rat, leading to increased brain 5-HT turnover as revealed by higher amounts of its metabolite, 5-HIAA. The ratio of brain Trp to plasma free Trp was decreased after 2 h of running. Liver Trp content rose only after 3 h of running, while liver unesterified fatty acid (UFA) concentrations remained unmodified. A comparison between food deprivation and running (both of which promote lipolysis) was performed. Running for 2 h affected to the same extent plasma Trp disposition when compared with 24 h food deprivation. Nevertheless, the ratio of brain Trp to plasma free Trp was decreased in the food-deprived rats, when compared to the runners. Nicotinic acid, which inhibits fat catabolism, completely abolished the plasma UFA increase induced by 1 h of running. The drug did not affect plasma free Trp, brain Trp, 5-HT or 5-HIAA but enhanced plasma total Trp level. Naloxone, an opiate antagonist, which decreased running-induced lipolysis, did not alter plasma Trp disposition. Desipramine, an antidepressant compound, affected only peripheral Trp concentrations of the runners. Plasma free and total Trp concentrations were increased in desipramine-treated runners, compared with saline-treated runners. In addition, desipramine increased the ratio of brain Trp to plasma free Trp of the runners. Brain 5-HT and 5-HIAA were increased in both desipramine-treated controls and runners. 9 The results suggest that running, which like food deprivatiQn accelerates lipolysis, increases brain Trp content and then 5-HT turnover. Comparison of these two physiological situations suggests that effectiveness of brain Trp entry is much more altered by fasting.

Plasma unesterified fatty acid and triacylglycerol concentration of the goat ( capra hircus) during pregnancy and lactation

1. 1. The concentrations of unesterified fatty acids and triacylglycerol were measured in plasma obtained from goats at various stages of pregnancy and lactation. 2. 2. The plasma unesterified fatty acid concentration increased during the last third of pregnancy: highest concentrations were found at parturition and during early lactation. 3. 3. The plasma triacylglycerol concentration showed a transient increase during mid-pregnancy: the concentration fell around parturition and no evidence for hypertriglyceridemia was found during latepregnancy. 4. 4. Results are compared with those of other studies of ruminant and non-ruminant species.

Delta 9- and delta 6-desaturase activities of the ovine placenta and their role in the supply of fatty acids to the fetus.

Although the fatty acid compositions of the total lipids of the sheep placenta and fetal plasma were shown to be broadly similar, they differed significantly from the fatty acid composition of the maternal plasma unesterified fatty acids, the plasma lipid component from which the fetus derives almost all of its requirements for pre-formed fatty acids. In particular, the placental and fetal plasma lipids displayed a 3-fold higher oleic acid/stearic acid ratio and contained a significantly higher proportion of arachidonic acid than the maternal unesterified fatty acids. These differences correlated well with the high delta 9- and delta 6-desaturase activities, respectively, shown to be present in sheep placental tissue in vitro. The levels of these enzymes in placental tissue contrasted with the relatively low desaturase activities found to be present in adult and neonatal sheep liver and in the placentas of other, non-ruminant, species. The possible role of such high levels of desaturase activity in the sheep placenta is discussed in relation to the particularly poor essential fatty acid status imposed upon the fetal ruminant.

Effects of maternal ethanol consumption on hepatic lipid biosynthesis in foetal and neonatal rats.

Effects of prolonged maternal ethanol consumption were studied on hepatic lipid content, on the rates of fatty acid synthesis and on the activities of enzymes involved in fatty acid synthesis in the livers of foetal and suckling neonatal rats. Prolonged maternal ethanol consumption resulted in a significant increase in the contents of hepatic total lipids, triacylglycerols and plasma unesterified fatty acids in foetal and neonatal rats. Studies in vitro with 3H2O showed that maternal ethanol consumption did not result in a significant change in its rate of incorporation into lipid fractions of foetal and neonatal livers. The rates of fatty acid synthesis showed a pronounced decrease immediately after birth, compared with the foetal stage, but increased in the adult animals. On the other hand, the highest rates of lipid oxidation were observed in the neonatal stage. Maternal ethanol consumption resulted in a significant decrease in the rates of [14C]palmitate oxidation to 14CO2 by both the foetal and neonatal livers. Maternal ethanol consumption did not result in an increase in the activities of any of the lipid-synthesizing enzymes tested throughout the period of development. Although increased fatty acid synthesis does not seem to be the mechanism for the accumulation of these lipids, decreased oxidation of the lipids may be partly responsible for the lipid accumulation.

Octadecenoic Fattv Acids and their Association with Hemolysis in Malaria

Octadecenoic fatty acids have been implicated in prehemolytic and hemolytic phenomena associated with malaria. Oleic [18:1 (n-9)] and cis-vaccenic [18:1 (n-7)] acids were found and quantified in the major neutral and phospholipids of the erythrocytes and plasmas of normal and Plasmodium lophurae-infected ducks, and in the parasite itself. The octadecenoic fatty acids were elevated over normal values in the major phospholipid classes of infected erythrocytes, in the erythrocyte-specific alkoxy phosphatidylethanolamine of infected erythrocytes, and in the plasma unesterified fatty acids, triacylglycerols, cholesterol esters and phosphatidlycholine of infected ducklings. Oleic acid was the major fatty acid of P. lophurae (33% total lipid fatty acid). Theoretical considerations of octadecenoic fatty acid modifications of erythrocyte membrane structure and function in malaria are discussed.

Fatty acid and tryptophan changes on disturbing groups of rats and caging them singly

The effects of disturbing groups of 24 hr fasted rats on plasma unesterified fatty acid (UFA) and tryptophan concentrations and brain tryptophan concentrations were investigated. Removing rats from cages rapidly increased plasma UFA and corticosterone and decreased plasma and whole blood tryptophan of cage mates. The disturbance also appeared to influence biochemical values of rats in other cages within the same chamber. Effects specific to individual cages were also suggested. In subsequent experiments 24 fasting rats caged together were rapidly transferred to 24 separate cages and killed at intervals. Plasma UFA rose to a maximum by 12 min and then tell toward initial values. Plasma total tryptophan concurrently fell then rose. Its percentage in the free (ultrafilterable) state, and in some experiments the absolute values of free tryptophan rose then fell. When the latter rise was marked then brain tryptophan and the 5-HT metabolite 5-hydroxyindoleacetic acid rose. Tyrosine changes were negligible. Thus altered brain tryptophan level and 5-HT metabolism may be associated with plasma tryptophan changes caused by brief environmental disturbance.

Influence of Dietary Fatty Acids on Liver and Adipose Tissue Lipogenesis and on Liver Metabolites in Meal-Fed Rats

Rats were trained to eat a fat-free high carbohydrate diet from 800 to 1100 hours each day. After adaptation to meal-eating, the fat- free diet was supplemented with 8% methyl stA©arate(Ci8;o) or 3% methyl linoleate (Ci8:2) for 7 days. Relative to the fat-free group, hepatic utiliza tion of acetate unit equivalents (C2 units) for fatty acid synthesis per mg soluble protein by the Ci8:o group was not significantly altered, whereas Ci8:2 supplementation significantly depressed hepatic fatty acid synthesis. Supplemental Ci8:2 also caused a significant decline in liver fatty acid synthetase and acetyl CoA carboxylase while fat-free and Ci8:o groups dis played similar enzyme activities. Within a treatment, C2 unit utilization tor in vivo fatty acid synthesis was identical to that of acetyl CoA car boxylase and fatty acid synthetase activities in vitro. Therefore, shortly after a meal, the hepatic activities of these two enzymes appear to be functioning at near capacity. Ci8:2 supplementation to the fat-free diet for 7 days caused a 25% decline in glucokinase and pyruvate kinase activ ities, but only pyruvate kinase was significantly depressed. In contrast, citrate cleavage enzyme and fatty acid synthetase were both significantly reduced in activity by 50%. Plasma unesterified fatty acid levels in rats fed Ci8:2 for 5 days were not significantly elevated prior to a meal, al though dietary Ci8:2 did cause a fourfold rise in plasma free linoleate. Quantitation of long chain acyl CoA esters in freeze-clamped liver tissue of rats fed fat-free or fat-free plus 3% Ci8:2 or Ci8:3 diets revealed no con centration differences between treatments either before or after a meal. Similarly, lactate and pyruvate concentrations as well as the lactate: pyru vate ratios were not significantly changed by dietary Ci8:2 or Ci8:3. The inhibitory effects of C18:2 or Ci8;3 appear not to be mediated through changes in total plasma free fatty acid levels, in total hepatic long chain acyl CoA concentration or in hepatic cytosolic redox state. J. Nutr. 107: 1277-1287, 1977.