myo-inositol action on gerbil intestine: alterations in alkaline phosphatase activity upon phosphatidylinositol depletion and repletion in vivo

The influence of phosphatidylinositol (PI) on intestinal alkaline phosphatase activity was studied in myo-inositol deficient gerbils. A reduction of membrane PI in intestinal mucosa to 30-40% of the control was produced by feeding female gerbils a myo-inositol-deficient diet containing coconut oil for 2 weeks. As expected, the animals developed typical intestinal lipodystrophy with abnormal fat accumulation. In the PI-depleted animal, intestinal alkaline phosphatase activity was reduced to 20-30% of the control group. The levels of both membranous and soluble enzymes in intestinal mucosa were affected, but there were no changes in liver, kidney and plasma levels. When the lipodystrophic gerbils were given dietary myo-inositol, the complete repletion of intestinal membrane PI to the control level occurred 36 h later, whereas membrane-bound alkaline phosphatase activity in intestine was not restored to the control level until 72 h later. Administration of cycloheximide or actinomycin D did not block this enzyme induction. Lymphatic output of triacylglycerol into the bloodstream was stimulated 10-fold at 18 h of myo-inositol repletion, but there was no parallel increase in the activity of alkaline phosphatase in plasma during this early phase of intestinal recovery. Thus, these data suggest a possible regulatory role of PI in the processing and/or turnover of alkaline phosphatase in vivo, but a negative role of alkaline phosphatase in lipid transport across gerbil intestine.     

Regulation by dietary choline of hepatic fatty acid synthetase in the rat

Fatty acid synthetase activity was measured in the high-speed supernatant fraction of liver homogenates from rats fed a semisynthetic diet low in lipotropic factors. If choline was omitted from the diet, a significant increase of fatty acid synthetase activity was observed after two feedings of the deficient diet. Compared with controls, the increase of fatty acid synthetase activity was of a magnitude that could account for the amount of triglyceride accumulating in the hepatic floating lipid fraction. Gas-liquid chromatographic analysis of the floating lipid triglycerides showed an increased content of palmitic acid due to choline deficiency; this increase could be predicted from the increased fatty acid synthetase activity and its known characteristic yield of palmitic acid.     

Nutritional and hormonal control of lung and liver fatty acid synthesis.

During starvation and in streptozotocin-induced diabetes, the total activities of rat lung acetyl CoA carboxylase and fatty acid synthetase are reduced to one-third of the normal values. Refeeding of the starved animals or administration of insulin to diabetic animals restores the levels to the original values. The insulin effect is dose and time dependent. These data contrast with those in the liver, where a 30- to 50-fold depression of these enzymes is observed in the diabetic state and administration of insulin is actually followed by doubling of the activity over normal controls. Fat-free high-fructose diet (containing 60% fructose by weight) enhances the activities of liver enzymes 3- to 6-fold over the values of controls on laboratory diet but has no effect on the lung enzymes. Long-term feeding of fructose diet also increases the activities of liver enzymes from diabetic animals to twice the value of normal controls on laboratory diet. Insulin administration to fructose-fed diabetic animals restores the enzyme activities to those obtained with fructose-fed normal controls. However, the stimulation of lung enzymes of diabetic animals can be effected either by fructose or by insulin. Antigen-antibody titrations and measurements of the rate of protein synthesis show that the increased activity of the lung and liver fatty acid synthetase is due to enhanced content rather than increased specific activity. These data suggest that insulin or fructose effects on fatty acid-synthesizing enzymes are mediated through intermediate(s) whose concentration is affected in the experimental diabetes. Furthermore, all tissues may not have stringent insulin requirements since the lung enzymes can be stimulated by fructose alone.     

Control of fatty acid synthetase mRNA levels in rat liver by insulin, glucagon, and dibutyl cyclic AMP

The quantity of translatable fatty acid synthetase mRNA in liver of rats subjected to different hormonal states was determined with a rabbit reticulocyte lysate cell-free translation system. Both membrane-free polysomal and total cellular poly (A)-containing RNA were translated. The level of translatable fatty acid synthetase mRNA was 11-fold or more lower in livers of diabetic rats than in similar animals treated with insulin. In contrast, both glucagon and dibutyl cyclic AMP caused a 3-fold reduction over controls in the amount of translatable fatty acid synthetase mRNA in livers of animals refed a fat-free diet for 12 hr. These changes are consistent with the previously reported alterations in the relative rates of fatty acid synthetase synthesis measured in vivo. This suggests that the changes in the amount of fatty acid synthetase that occur in liver in response to the above hormonal changes are primarily due to changes in the amount of mRNA coding for this enzyme.     

Early effect of myo-inositol deficiency on phosphatidylinositol metabolism in rat liver

Young rats (100 g) were fed either a myo-inositol-deficient or supplemented (control) diet for up to 14 days following a 12 h fast. At various times during this period animals were killed, livers were removed, and a microsomal fraction was prepared and assayed for CDPdiacylglycerol inositol transferase activity and for phosphatidylinositol-inositol exchange activity. Within 2 days after beginning the regimen, rats consuming the deficient diet had a 40% lower activity of the transferase than rats consuming the control diet. This difference was maintained throughout the feeding period and developed simultaneously with the accumulation of triacylglycerol in the deficient livers. In contrast, the specific activity of the exchange enzyme was unchanged by feeding the deficient diet.     

The effects of experimental inflammation on adaptive synthesis of rat liver fatty acid synthetase

The effects of experimental inflammation, induced by subcutaneous injection of oil of turpentine, on adaptive synthesis of rat liver fatty acid synthetase were investigated. Liver levels of α₁-acid glycoprotein, an “acute-phase” protein known to be synthesized at an accelerated rate as a result of inflammation, were also measured. The increase in fatty acid synthetase activity in livers of rats which were starved and then fed a fat-free diet was suppressed to an extent dependent on the periods between fat-free feeding and inflammation and inflammation and sacrifice. Inflammation induced 2 h after refeeding gave complete suppression, whereas inflammation after 10 h of fat-free feeding had no suppressive effect. When induced 2.5 or 7.5 h after refeeding, inflammation led to partial suppression of the increase in fatty acid synthetase activity. The increase in liver α₁,-acid glycoprotein levels characteristic of inflammation was reduced in animals inflamed 7.5 or 10 h after fat-free feeding, but was unaffected when inflammation was induced 2.5 h after refeeding. The ratio of free to membrane-bound polyribosomes in liver increased from 0.77 in rats which were neither starved nor fed a fat-free diet to 3.31 in rats which were starved and then fed a fat-free diet for 15 h. When inflammation was induced 2.5 h after refeeding, the ratio increased to only 1.74 after 15 h of refeeding. Inflammation resulted in a marked reduction in the level of glycogen in the liver, regardless of the time of induction of inflammation and the dietary status of the animal.     

Effect of a high-fat diet with partially hydrogenated fish oil on long-chain fatty acid metabolizing enzymes in subcellular fractions of rat liver

Hepatic metabolism of long-chain fatty acids were studied in young male rats fed a semisynthetic diet containing 20% (w/w) partially hydrogenated fish oil (PHFO)2, with or without 2% (w/w) linoleic acid. The enzymic activities involved in the formation and breakdown of long-chain acyl-CoA were both increased in the animals fed the semisynthetic diet, compared to pellet-fed control animals. Thus, the specific palmitoyl-CoA synthetase activity increased slightly in both the mitochondrial (1.4-fold) and the microsomal (1.6-fold) fractions. In the peroxisome-enriched fraction the activity was increased (about 2.6-fold) only on addition of linoleic acid to the diet. The data are consistent with an increased catabolism of long-chain fatty acids by a peroxisomal and a mitochondrial pathway. Thus, the total carnitine palmitoyltransferase activity increased 2-fold in the mitochondrial fraction, and was partly prevented by added linoleic acid. Peroxisomal beta-oxidation activity was also increased (about 7-fold) in livers of PHFO-fed rats, but did not change when linoleic acid was added. The PHFO-fed rats also revealed elevated capacity for hydrolysis of palmitoyl-CoA in both the mitochondrial (2.4-fold) and the cytosolic (2.0-fold) fractions and the latter was almost completely and selectively prevented by added linoleic acid. The s values of mitochondria and peroxisomes varied with the dietary regime, and some of the observed changes in the specific activities of the fatty acid metabolizing enzymes with multiple subcellular localization can be explained as an effect of changes in the s values of the organelles. Thus, the s value of mitochondria increased 1.8-fold as a result of PHFO feeding, but was fully prevented by linoleic acid in the diet. On the other hand, the s values of peroxisomes decreased by about 50% on feeding a PHFO diet, and by about 25% with added linoleic acid.     

Effect of copper deficiency and Sodium intake upon liver lipid and mineral composition in the rat

The effect of copper and sodium intake upon liver cholesterol concentrations, fatty acid profile, and mineral concentrations were studied in the Long-Evans rat. Forty-eight male weaning rats were divided into three groups of 16 each and fed a semipurified diet containing either 0, 3, or 8 mg of added copper/kg of diet. At 100 d of age, half of the animals in each group were given 1% NaCl as drinking water and the other half was given deionized-distilled water for 12 wk. Copper deficiency in rats produced elevations in liver palmitate and oleate concentrations, but decreases in linoleate concentrations. The ratio of oleate:stearate was higher in copper deficient rats. Liver copper levels were decreased, but liver iron concentrations were elevated in copper deficient rats. Sodium intake did not have an effect on any of the parameters studied. These results suggested that dietary copper deficiency alters both liver mineral and fatty acid composition.     

The effect of essential fatty acid deficiency upon fatty acid uptake by the brain.

Young adult rats, either control or essential fatty acid deficient, were administered either [3-H] oleic acid or [3-H] arachidonic acid by stomach tube. In addition, a group of control rats was given [3-H] palmitic acid. The rats were killed at various times therafter, and the radioactivity of the lipids of brain and plasma was examined. In confirmation of previous work, the blood lipid label was found to rise rapidly and then fall, wheras the activity of brain lipids increased slowly and did not show a decline through the 24-h period studied. Analysis of the brain uptake data according to first-order kinetics confirmed the impressions gained from visual inspection of the data. The initial rate of uptake of arachidonic acid was about 4.5 times that of oleic acid in control animals and in deficient animals. Essential fatty acid deficiency, however, did not induce an altered rate of uptake for either oleic acid or arachidonic acid. The rate of uptake of palmitic acid by control rats was not significantly different from that of oleic acid. Even though the initial rates of incorporation of oleic and arachidonic acids were not changed during essential fatty acid deficiency, the final levels of radioactivity obtained in brain lipids were higher in deficient rats with both fatty acids. The plateau value obtained with oleic acid was 1.5 times higher in deficient animals, while the plateau value for arachidonic acid was 1.7 times higher. An experiment in which deficient animals were allowed access to a control diet for 12 or 24 h prior to the labeling experiment suggested that the higher levels of radioactivity found in brain lipids of deficient animals was not due to an isotope dilution effect. Such animals still displayed the labeling pattern of deficient animals with arachidonic acid, while the results with oleic acid varied somewhat. Our results suggest that essential fatty acid deficiency does not alter the ability of the brain to take up the fatty acids studied. However, the fatty acids, especially arachidonic, are retained in the brain to a greater extent in the deficient animals.     

Studies on the mechanism of the effects of experimental inflammation on adaptive synthesis of rat liver fatty acid synthetase

The mechanism of suppression, by experimental inflammation of the usual increase in hepatic fatty acid synthetase activity resulting from fat-free feeding following starvation (adaptive synthesis), was investigated immunochemically. That suppression results from changes in amount of hepatic fatty acid synthetase was shown by the observation that fatty acid synthetase preparations from inflamed and uninflamed animals, exhibiting a wide variety of specific enzyme activities, had identical immunochemical equivalence points. In confirmation of this, the amounts of fatty acid synthetase, determined by radial immunodiffusion in gels containing anti-fatty acid synthetase serum, varied concomitantly with changes in enzyme activity regardless of the relative times of inflammation and onset of adaptive synthesis. Serum insulin levels were not dramatically elevated during the first 48 h of fat-free feeding, but rose markedly thereafter. Inflammation, either alone or combined with fat-free feeding, resulted in increased serum glucose levels, followed by a similar pattern of increased serum insulin levels some 12 h later. Fat-free feeding did not affect serum cortisol levels, but depressed liver cyclic AMP. Inflammation invariably resulted in a marked increase in serum cortisol within 12 h and a concomitant elevation of hepatic cyclic AMP, indicating possible roles for cortisol and cyclic AMP in suppression of hepatic fatty acid synthetase synthesis.     

Effects of gamma-linolenic acid supplementation on lipogenesis regulation in pregnant zinc-deficient rat and fetus

In the liver of zinc-deficient pregnant rats fatty acid synthetase and delta 9-desaturase activities decreased and diet supplementation with gamma-linolenic acid potentiated this effect. However, in liver microsomes from the foetuses of zinc-deficient mothers, HMG CoA reductase and delta 9-desaturase activities declined but fatty acid activity rose. The same applied to foetuses from mothers whose diet was supplemented with gamma-linolenic acid and here again, the effect of zinc deficiency was potentiated. The fact that delta 9 activity dropped whereas fatty acid synthetase activity rose implied a defect in the mechanism regulating the functioning of these enzymes. In the non zinc-deficient group of pregnant females, gamma-linolenic acid supplementation had no effect on fatty acid synthetase and delta 9-desaturase activities but significantly increased HMG CoA reductase activity. In foetuses from the same group, the activities of MHG CoA reductase, delta 9-desaturase and fatty acid synthetase all increased.     

A phytol-enriched diet induces changes in fatty acid metabolism in mice both via PPARalpha-dependent and -independent pathways

Branched-chain fatty acids (such as phytanic and pristanic acid) are ligands for the nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARalpha) in vitro. To investigate the effects of these physiological compounds in vivo, wild-type and PPARalpha-deficient (PPARalpha-/-) mice were fed a phytol-enriched diet. This resulted in increased plasma and liver levels of the phytol metabolites phytanic and pristanic acid. In wild-type mice, plasma fatty acid levels decreased after phytol feeding, whereas in PPARalpha-/- mice, the already elevated fatty acid levels increased. In addition, PPARalpha-/- mice were found to be carnitine deficient in both plasma and liver. Dietary phytol increased liver free carnitine in wild-type animals but not in PPARalpha-/- mice. Investigation of carnitine biosynthesis revealed that PPARalpha is likely involved in the regulation of carnitine homeostasis. Furthermore, phytol feeding resulted in a PPARalpha-dependent induction of various peroxisomal and mitochondrial beta-oxidation enzymes. In addition, a PPARalpha-independent induction of catalase, phytanoyl-CoA hydroxylase, carnitine octanoyltransferase, peroxisomal 3-ketoacyl-CoA thiolase, and straight-chain acyl-CoA oxidase was observed. In conclusion, branched-chain fatty acids are physiologically relevant ligands of PPARalpha in mice. These findings are especially relevant for disorders in which branched-chain fatty acids accumulate, such as Refsum disease and peroxisome biogenesis disorders.     

CHANGES IN PHOSPHOGLYCERIDE FATTY ACIDS OF RAT BRAIN INDUCED BY LINOLEIC AND LINOLENIC ACIDS AFTER PRE- AND POST-NATAL FAT DEPRIVATION

Abstract— Pregnant rats were maintained on a fat-free diet, starting at 10–12 days after impregnation and the offspring continued on the diet during a developmental period of 120 days. Brain fatty acids showed decreases in the level of (n-3) and (n-6) fatty acids of brain phophoglycerides, except for 22:5 (n-6) which increased. These changes preceded an increase in the (n-9) fatty acids (20:3 and 22:3). Supplementation with either linoleic or linolenic acid for 10 or 30 days after induction of the deficiency state caused an increase in the (n-6) and (n-3) fatty acids respectively, to control levels. The level of 22:5 (n-6) was increased additionally by linoleic supplementation while linolenic refeeding to deficient animals decreased 22:5 (n-6) to near control levels. The anomalous results obtained on 22:5 (n-6) with 18:3 (n-3) supplementation is attributed to competitive inhibition of linoleate desaturation by linolenate. Linoleic and linolenic acid were equally effective in reducing the elevated levels of the (n-9) fatty acids toward control levels, although control levels with either fatty acid was not reached after 30 days supplementation. The increase of the (n-6) and (n-3) fatty acids to normal values precedes the decrease of (n-9) fatty acids following supplementation of linoleic or linolenic acid to fat-deficient rats. No change in fatty acid composition in control animals between 30 and 120 days was observed. In fat deficient as well as supplemented animals the total saturated, monounsaturated and polyunsatur-ated fatty acid composition was constant as was the unsaturation index.     

Rapid induction of vitamin A deficiency in rabbits

Clinical and biochemical evidence of vitamin A deficiency was produced in rabbits as early as 4-5 weeks after weaning to a vitamin A deficient diet from dams maintained during lactation on the deficient diet. Mean serum retinol levels at the time of weaning for the deficient dams were 25 +/- 6 micrograms/dl compared with 74 +/- 8 micrograms/dl for the controls. Five weeks after weaning, 25% of pups fed the vitamin A deficient diet had ocular lesions characterized by the accumulation of sloughed epithelium on the cornea. At this time, mean serum values of the pups were 10 +/- 4 micrograms/dl for the deficient group and 73 +/- 8 micrograms/dl for the controls. Evidence of critically depleted liver stores was documented in the deficient rabbits by an elevated relative dose response test (54 +/- 18%) that did not occur in the control group (6 +/- 5%). Although food consumption was similar, weight gain was lower in the deficient group when compared to the control group.     

Fat absorption in essential fatty acid deficiency: a model experimental approach to studies of the mechanism of fat malabsorption of unknown etiology

Male rats were made deficient in essential fatty acids by feeding them a fat-free diet supplemented with 4% tripalmitin for 8-12 wk from the time of weaning. After feeding 0.5 ml of [(14)C]triolein or [(3)H]oleic acid, 72-hr stool recoveries of radioactivity were significantly greater in deficient rats than in chow-fed controls. Essential fatty acid deficiency did not reduce the absorptive capacities for triolein or for a medium-chain fat, trioctanoin, measured after 3 and 2 hr of maximal-rate duodenal infusion. In everted jejunal slices from essential fatty acid-deficient rats, uptake of micellar [(14)C]oleic acid at 0-1 degrees C was similar to that of controls, but the rate of incorporation of fatty acid into triglyceride after rewarming to 37 degrees C was significantly reduced. The specific activities of the microsomal esterifying enzymes, acyl CoA:monoglyceride acyltransferase and fatty acid CoA ligase in jejunal mucosa were 30% lower in essential fatty acid-deficient rats. However, the total microsomal enzyme activity adjusted to constant weight did not differ significantly in deficient rats compared with controls. After intraduodenal perfusion of triolein, accumulation of lipid in the intestinal wall was increased in the deficient rats. Because over 90% of the absorbed mucosal lipid was present as triglyceride, essential fatty acid deficiency appears to affect the synthesis or release of chylomicron lipid from the intestine. Analysis of regions of intestine showed that this delay in transport was most marked in the midportion of the small intestine.     

BRAIN RECOVERY FROM ESSENTIAL FATTY ACID DEFICIENCY IN DEVELOPING RATS 1

Abstract— Rats were supplied from before birth with an essential fatty acid (EFA) deficient, a control, or an EFA deficient-control combination diet for various periods up to 6 months. It was found that EFA deficiency resulted in brain weights decreased in comparison with control values throughout development. The brain weight/body weight relationship, however, expressed by Donaldson's equation was generally maintained in animals fed either totally deficient or control diets. Animals deficient even during the brain's most actively growing period were able to recover completely on restoration of the control diet for a sufficiently long period. Fatty acid alterations in brain ethanolamine phosphoglyceride (EPG) during EFA deficiency were extensive. Acids of the ω6 family (18:2, 20:2, 20:3, 20:4, 22:3, 22:4 but not 22:5) were reduced from control figures. In the w9 family 20:3 and 22:3 were especially elevated whereas 22:6 ω3 levels were similar to those of the controls, finally decreasing only after a lengthy period of EFA deprivation. Mean unsaturation contents, as expressed by the proposed unsaturation index notation (Ul_mol) agreed closely in EPG fatty acids of deficient and control rats at a particular age. On substitution of the control for the deficient diet the ω6 family rebounded in a manner such that values for 20:4, 22:4, and 22:5 exceeded comparable figures in control animals. Concomitantly the ω9 family receded below control levels, and ω3 acids remained or returned to normal. This overadjustment in ω6 and ω9 families continued even after a prolonged period on the control diet.     

Polyunsaturated fatty acids do not activate AMP-activated protein kinase in mouse tissues

Stearoyl-CoA desaturase 1 (SCD1) deficiency partitions fatty acids away from lipid synthesis towards fatty acid oxidation in liver and skeletal muscle in part due to activation of AMP-activated protein kinase (AMPK) pathway. The mechanism of AMPK activation by SCD1 mutation is unknown, however since SCD1-/- animals have increased relative amounts of polyunsaturated fatty acids (PUFA), we hypothesized that the increased levels of PUFA might be responsible for the activation of AMPK in SCD1 deficient mice. Therefore, the present study was undertaken to analyze the effect of PUFA on AMPK in liver, skeletal muscle, and heart. We fed mice ad libitum for 14 days with diet supplemented with fish oil (5% fat). As expected, fish oil supplementation significantly increased n-3 PUFA content in each of the analyzed tissues. Hepatic mRNA levels of fatty acid synthase and acyl-CoA oxidase decreased by 92% and increased by 60%, respectively, consistent with known PUFA effects. However, after 14 days of PUFA feeding, we did not find any changes in AMPK phosphorylation and protein content in mouse liver, skeletal muscle, and heart. The data suggest that PUFA are not involved in AMPK activation in mouse tissues and that the increased activity of AMPK in SCD1-/- mice is probably PUFA-independent.     

Effects of dietary carbohydrate and myo-inositol on metabolic changes in rats fed 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane (DDT)

This study was conducted to examine the effects of dietary carbohydrate [starch or sucrose (500 g/kg diet)] and myo-inositol (2 g/kg diet) on metabolic changes in rats fed 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane (DDT) (0.7 g/kg diet). Dietary DDT enhanced serum and hepatic lipids and hepatic thiobarbituric acid reactive substances (TBA-RS), elevated hepatic activities of lipogenic enzymes such as malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) and fatty acid synthetase (FAS), increased hepatic cytochrome P-450 content and the activities of drug-metabolizing enzymes such as aminopyrine N-demethylase, glutathione S-transferase and 4-nitrophenol-UDP glucuronosyltransferase (4NP-UDPGT) and raised hepatic ascorbic acid and serum copper. Dietary sucrose promoted the increases in hepatic concentrations of total lipids, triglyceride and cholesterol, hepatic activity of ME, hepatic TBA-RS, cytochrome P-450 content and serum copper due to DDT feeding when compared to DDT administered in a starch based diet. Dietary myo-inositol significantly depressed the rises in hepatic concentrations of total lipids, triglyceride and cholesterol and the activities of ME and G6PD due to DDT feeding regardless of dietary carbohydrate quality. Dietary starch supplemented with myo-inositol potentiated the enhancements in hepatic activities of Phase II drug-metabolizing enzymes such as glutathione S-transferase and 4NP-UDPGT due to DDT feeding. These results suggest that dietary starch and myo-inositol can protect DDT fed rats against an accumulation of hepatic lipids, which might be mainly ascribed to the depression of hepatic lipogenesis. In addition, the present study implies that the supplementation of myo-inositol to high starch diet might improve the function of drug-metabolizing enzymes exposed to DDT.     

Dietary n-6 PUFA deprivation for 15 weeks reduces arachidonic acid concentrations while increasing n-3 PUFA concentrations in organs of post-weaning male rats

Few studies have examined effects of feeding animals a diet deficient in n-6 polyunsaturated fatty acids (PUFAs) but with an adequate amount of n-3 PUFAs. To do this, we fed post-weaning male rats a control n-6 and n-3 PUFA adequate diet and an n-6 deficient diet for 15 weeks, and measured stable lipid and fatty acid concentrations in different organs. The deficient diet contained nutritionally essential linoleic acid (LA,18:2n-6) as 2.3% of total fatty acids (10% of the recommended minimum LA requirement for rodents) but no arachidonic acid (AA, 20:4n-6), and an adequate amount (4.8% of total fatty acids) of α-linolenic acid (18:3n-3). The deficient compared with adequate diet did not significantly affect body weight, but decreased testis weight by 10%. AA concentration was decreased significantly in serum (− 86%), brain (− 27%), liver (− 68%), heart (− 39%), testis (− 25%), and epididymal adipose tissue (− 77%). Eicosapentaenoic (20:5n-3) and docosahexaenoic acid (22:6n-3) concentrations were increased in all but adipose tissue, and the total monounsaturated fatty acid concentration was increased in all organs. The concentration of 20:3n-9, a marker of LA deficiency, was increased by the deficient diet, and serum concentrations of triacylglycerol, total cholesterol and total phospholipid were reduced. In summary, 15 weeks of dietary n-6 PUFA deficiency with n-3 PUFA adequacy significantly reduced n-6 PUFA concentrations in different organs of male rats, while increasing n-3 PUFA and monounsaturated fatty acid concentrations. This rat model could be used to study metabolic, functional and behavioral effects of dietary n-6 PUFA deficiency.     

Lipid metabolism in fatty liver of lysine- and threonine-deficient rats

Rats were fed a low protein diet deficient in and supplemented with lysine and threonine. Liver lipids contained more lecithin, sphingomyelin, and free fatty acids, and less amino phospholipids in the deficient rats. No variations in fatty acid composition of choline- and ethanolamine-containing phospholipids were found; only palmitic acid was increased in the serine-containing phospholipids of the deficient animals. The incorporation of acetate-(14)C into phospholipids, but not into other liver lipids, was lower in deficient rats. In the plasma of deficient rats the concentration of esterified fatty acids and phospholipids was lower, of free fatty acids higher, than in the controls. The fatty acid composition of depot fat differed from that of liver neutral fat both in deficient and supplemented animals. The results presented establish that multiple metabolic defects resulting from lysine and threonine deficiency accompany the fatty liver. The design of the experiments does not permit conclusions to be drawn regarding the causal relationship between the various alterations in lipid metabolism and the fatty liver.