Reduced plasma lecithin cholesterol acyl transferase activity in rats fed iron-deficient diets

An iron-deficient diet containing no fat (FF?Fe) or containing either 14% hydrogenated coconut oil (HCNO?Fe) or 14% corn oil (CO?Fe) was fed to separate groups of rats for 10 weeks. In the control group, the corresponding iron-supplemented diets were fed FF+Fe, HCNO+Fe, CO+Fe. When rats were fed iron-deficient diets, their plasma lecithin cholesterol acyl transferase (LCAT) activity was significantly reduced as compared to controls. Their plasma also contained relatively more cholesteryl esters (CE) than free cholesterol (CH). In rats fed FF+Fe and CO+Fe diets, plasma contained similar levels of CE and CH. In those fed HCNO+Fe diet, plasma had 40% less CE than CH. Red cell CH content was significantly greater in the CO?Fe group. Iron deficiency, as indicated by low blood hemoglobin (Hb) and hematocrit (Hct) values, was also observed only in this group. The triglyceride and phospholipid contents of plasma in rats fed iron-deficient diets were significantly lower than of those in the control groups. Thus, changes in LCAT activity and CE/CH ratio in plasma showed the effect of iron-deficient diet consumption even before the blood Hb and Hct levels were reduced.     

Reduction of essential fatty acid deficiency in rats fed a low iron fat free diet

Young male rats were fed ad libitum for 8 weeks a low iron fat-free (FF-Fe) diet or a fat-free diet supplemented with iron (FF+Fe). The relative levels of 16∶1 to 16∶0 and 18∶1 to 18∶0 in the total fatty acids of liver and other tissues (plasma, erythrocytes and intestinal mucosa) were considerably decreased because of a lack of dietary iron. In rats fed the FF-Fe diet, the levels of essential fatty acids (18∶2ω6+20∶4ω6) in tissues were 2-to 3-fold greater than in the corresponding tissues of rats fed the FF+Fe diet. Eicosatrienoic acid (20∶3ω9) levels in tissue lipids from rats fed the FF+Fe diet were high (8–16%), whereas they were low (2–5%) in the case of animals fed the FF-Fe diet. The proportion of 20∶4 in total fatty acids of tissues was 2-to 3-fold greater in rats fed the FF-Fe diet than when they were fed the FF+Fe diet. Therefore, the relative levels of 20∶3ω9/20∶4ω6 varied from 1-2.9 in tissue lipids of rats fed the FF+Fe diet, while it varied only from 0.2–0.3 in animals fed the FF-Fe diet. These results suggest that a lack of dietary iron may reduce the synthesis of 16∶1, 18∶1, 20∶3 and 20∶4 and the metabolism of 20∶4.     

The synthesis and biological activity of thiolcarnitine and its thiolesters

Acetyl-D,L-thiolcarnitine was synthesized by the acid-catalyzed addition of thiolacetic acid to 4-trimethylammonio-2-butenoic acid. Acetyl-D,L-thiolcarnitine was the precursor of D,L-thilcarnitine, which was prepared by base hydrolysis. Thiolcarnitine significantly enriched in the L-isomer was prepared from acetyl-D,L-thiolcarnitine using carnitine acetyltransferase as the resolving agent. The C₂, C₈ and C₁₆ carnitine thiolesters were obtained by acylating thiolcarnitine with the corresponding N-hydroxysuccinimide esters. As a substrate for carnitine acetyltransferase, acetylthiolcarnitine gave the same kinetic constants as did acetylcarnitine; on the other hand, thiolcarnitine and carnitine gave the same K_m but the V_max with thiolcarnitine was less than 5% of the value obtained with carnitine. With thiolcarnitine and acetylthiolcarnitine as reactants, the measured K_eq, at 30 C and pH 7.0, for the reaction catalyzed by carnitine acetyltransferase (see below) was 4.6±.1. acetylthiolcarnitine+CoA—acetyl-CoA+thiolcarnitine     

Regulation of polyunsaturated fatty acid metabolism in tissue phospholipids of obese (fa/fa) and lean (fa/−) Zucker rats. 1. Effect of dietary lipids on cardiac tissue

The present investigation addressed three questions: (i) Does the obese syndrome alter the fatty acid composition of cardiac tissue and membrane phospholipids in obese (fa/fa) rats? (ii) Are changes, if they occur, similar to those reported for tissues of the genetically obese (ob/ob) mouse? (iii) Can cardiac tissue phospholipids and their component fatty acids be modified by dietary lipids and if so does this occur to the same extent in both fa/fa and lean (Fa/?) rats? Proportions of polyunsaturated fatty acids (PUFA) in cardiac total phospholipids of fa/fa rats differed significantly from those of Fa/? rats and from those reported for ob/ob mice. Increased 18∶2n?6 and decreased 20∶4n?6 and 22∶6n?3 in fa/fa rats indicated impaired PUFA metabolism, possibly reduced Δ6 and/or Δ5 desaturase activity, compared with Fa/? rats. No differences in hepatic Δ6 and Δ5 desaturase activity between fa/fa and Fa/? were found but enhanced activity of Δ9 desaturase activity in fa/fa as compared to Fa/? was evident. Inclusion of sunflower oil (SO) or triolein (TO) at 5% and 20% by weight in the diet elicited marked changes in the fatty acyl composition of cardiac phospholipids in both fa/fa and Fa/? rats when compared with animals fed the control Oxoid diet alone. Supplementation with triolein was most effective, reducing 18∶2n?6 and increasing 20∶4n?6 proportions in fa/fa rats so that they resembled those in Fa/? rats fed the control Oxoid diet. The type of fat rather than the amount of its dietary intake appears to be the main determinant of the observed changes in phospholipid composition. Pair feeding hyperphagic fa/fa rats to the lower intakes of Fa/? rats did not abolish the characteristic differences in the proportions of PUFA in cardiac phospholipids between the two phenotypes. The effect of triolein on cardiac phospholipid fatty acid composition in the present studies is intriguing and may be relevant in understanding the beneficial role of dietary olive oil in ameliorating cardiovascular disease in man.     

Hypolipidemic effects of clofibrate and selected chroman analogs in fasted rats: II. High sucrose-fed animals

The hypolipidemic properties of ethyl 6-chlorochroman-2-carboxylate (II), 6-phenylchroman-2-carboxylate (III) and 6-cyclohexylchroman-2-carboxylate (IV) were compared to clofibrate (I) in sucrose-fed fasted male Sprague-Dawley rats. All compounds were administered at doses of 0.2 and 0.4 mmol/kg, orally, twice daily for 7 consecutive days. In this model, II was a more effective hypocholesterolemic drug than clofibrate, whereas III and IV were inactive. Chlorochroman II, like clofibrate, decreased serum α-lipoprotein cholesterol and pre-β-lipoprotein triglyceride concentrations and concomitantly increased serum β-lipoprotein triglyceride concentrations. In clofibrate-treated rats, serum free cholesterol concentrations increased concurrent with a reduction in serum lecithin: cholesterol acyltransferase activity, but no such correlation was observed for II. Only II lowered liver cholesterol levels and increased liver triglyceride levels. No consistent inhibition of liver microsomal 3-hydroxy-3-methylglutaryl-CoA reductase activity was observed with these analogs. The observed changes in triglyceride and cholesterol concentrations among serum lipoproteins were of a greater magnitude after chlorochroman II and clofibrate administration to sucrose-fed rats than in our previous studies using chow-fed fasted rats. These data suggest that chloro-substitution at the 6-position of the phenylchroman ring is important for hypolipidemic activity of these cyclic clofibrate analogs.     

Reduction in medium chain acids and monoenoic acids in livers and plasma of rats fed eicosa-5,8,11,14-tetraynoic acid

Male Sprague-Dawley rats were fed for 8 weeks a corn oil (CO) diet or a hydrogenated coconut oil (HCNO) diet. These diets were fed in the absence or presence of eicosa-5,8,11,14-tetraynoic acid (TYA). The inclusion of TYA in the HCNO diet reduced the levels of 12∶0 and 14∶0 in the total fatty acids of livers and plasma. With either diet, the presence of TYA caused an alteration in the fatty acid composition of these tissues so as to reduce the values of the ratios: 16∶1/16∶0, 18∶1/18∶0, and 20∶4/18∶2. These results suggest that dietary TYA can influence the hepatic metabolism of medium chain fatty acids and that it may inhibit the desaturase enzyme involved in the synthesis of not only 20∶4 but also of monoenoic fatty acids.     

Effects of dietary triolein and sunflower oil on insulin release and lipid metabolism in zucker rats

Obese and lean male Zucker rats were fed ad libitum on diets containing either 50 (L) or 200 (H) g/kg diet of either triolein (T) or sunflowerseed oil (S). The specific activity of the hepatic microsomal Δ9 desaturase enzyme was depressed in both lean and obese rats fed the HS diet compared with the other three diets. The fatty acid composition of liver and subcutaneous white adipose tissue lipids were consistent with a lower Δ9 desaturation activity in rats fed the H diets, particularly for the HS diet. In both genotypes, microsomal Δ9 desaturase activity and the ratio of 16∶1/(16∶0+16∶1) fatty acids in liver lipids were inversely related to the proportion of 18∶2 in liver lipid. Plasma insulin concentrations and rates of glucose-stimulated insulin release in vivo were higher in obese rats compared with lean rats, and plasma insulin levels were higher in rats fed S compared with T. There was no relationship between Δ9 desaturase activity and either plasma insulin concentration or rates of insulin release in vitro. These findings suggest that hepatic Δ9 desaturase activity of Zucker rats is responsive to changes in the proportion of 18∶2 in liver lipids but is not affected by changes in insulin secretion.     

Enzymatic acylation of ether and ester lysophospholipids in rat liver microsomes

The acylation of lysophospholipids by rat liver acyltransferases was studied. A comparison between ester and ether lysophospholipids as substrates revealed large differences in substrate properties. For instance, oleic acid from oleoyl-CoA and arachidonic acid from arachidonoyl-CoA were not incorporated into 1-O-octadecyl-sn-glycero-3-phosphocholine under experimental conditions that allowed an optimal transfer of oleic acid and arachidonic acid to 1-O-palmitoyl-sn-glycero-3-phosphocholine. However, we observed an acyl-CoA-independent transfer of arachidonic acid from 1-O-stearoyl-2-O-arachidonoyl-sn-glycero-3-phosphoinositol to 1-O-octadecyl-sn-glycero-3-phosphocholine.     

Diet-induced alterations in the discoid shape and phospholipid fatty acid compositions of rat erythrocytes

For eight weeks young male rats were fed diets rich in 18∶2 (stock diet, or 10% corn oil, CO) or those devoid of 18∶2 (fat free, FF, or 10% hydrogenated coconut oil, HCNO). The CO and HCNO diets were fed in the absence or presence of eicosa-5,8,11,14-tetraynoic acid (TYA). When 18∶2 was excluded, an increase in the level of 16∶1, 18∶1 and 20∶3 and a decrease in 18∶2 was observed in the fatty acids of red cells. On feeding TYA, an increase in 18∶2 and in the case of the HCNO+TYA diet, a decrease of 12∶0 and 14∶0 was also observed. In all cases the levels of 20∶4 in erythrocyte fatty acids were similar. Saturated fatty acids were predominant in phosphatidyl choline (PC), lysophosphatidylcholine, (LPC) and sphingomyelin whereas unsaturated acids were predominant in phosphatidyl ethanolamine (PE), (PS), and phosphatidyl inositol (PI). Acids containing three or more double bonds comprised about 90% of the total acids in PI. In all the phospholipids, the characteristic changes in the composition of fatty acids were observed due to the exclusion of 18∶2 from the diet. However, changes due to the feeding of TYA were found only in PC and LPC. In rats fed the 18∶2-rich diet, about 60% of the red cells were discocytes. In those fed the 18∶2-free diet, the level of discocytes decreased to about 23%, and the levels of echinocytes II and III increased. The exclusion of 18∶2 for even a few days decreased the proportion of discocytes. The loss of discoid shape was reversed in a few days by feeding an 18∶2-rich diet. Fatty acid analysis of erythrocytes of rats of the various dietary manipulations showed that the change in the proportion of discocytes followed the change in the level of 18∶2.     

Unsaturated fatty acids in the postnatally developing rat lung

Fatty acid desaturase activity specific for the C-9 position is present in lung microsomes prepared from rats of all ages. This activity is significantly lower in neonatal rat lung compared with adult lung. A rapid increase in C-9 fatty acid desaturase activity seen at the approximate time of weaning may be related to a decrease in the polyunsaturated fatty acid (PUFA) content of the diet as the rat begins to consume laboratory chow instead of mother's milk. The 900×g supernatant fraction of rat lung parenchymal cell homogenates is capable of incorporating linoleate, linolenate, and arachidonate into both triacylglycerols and phospholipids. Lung tissue from rats less than 20 days old incorporates these PUFA into phospholipids at a greater rate than lung, tissue from adult rats. The incorporation of these PUFA into phospholipids in neonatal lung tissue occured at a greater rate than their incorporation into triacylglycerols. In contrast, lung tissue from adult rats incorporated PUFA into triacylglycerols at a greater rate than into phospholipids. These data show that PUFA, known to be elevated in neonatal rat lungs, are used primarily for phospholipid biosynthesis in neonatal lung tissue whereas in adult lung tissue they are preferentially esterified to glycerol.     

The effect of dry heat on the bioavailability of iron in soy flour

Bioavailability of iron in soy flour was investigated by the Hemoglobin Regeneration Efficiency (HRE) procedure in 50 three-month-old Sprague-Dawley rats. Rats weighing 250 ±7 g and with a mean hemoglobin level of 12.9 g/dl were randomly assigned to one of five treatment groups: baseline (BL), unheated soy flour (UH), soy flour heated at 225°F for either 10 min (H10), 30 min (H30), or 120 min (H120). The animals were fed diets (46 ppm iron) containing the soy flour for 21 days. HREs of UH, H10, H30, H120 diets were 17.6, 16.8, 17.7 and 16.8%, respectively. Apparent iron absorption from the UH, H10, H30 and H120 diets was 94.7, 94.3, 93.9 and 94.3%, respectively. Serum iron was significantly lower (p<.001) and total iron binding capacity was significantly higher (p<.001) in rats fed the H120 diet. Iron concentrations in the liver, spleen, heart and kidney were significantly lower in rats fed H30 or H120 diets. These results suggest that prolonged heating of soy flour may reduce iron bioavailability and result in depletion of iron stores.     

Different degrees of moderate iron deficiency modulate lipid metabolism of rats

Severe iron deficiency affects lipid metabolism. To investigate whether moderate iron depletion also alters lipid variables—including lipid levels in serum and liver, hepatic lipogenesis, and fatty acid composition indicative of an impaired desaturation—we carried out experiments with rats fed 9, 13, and 18 mg iron/kg diet over a total of 5 wk. The study also included three pair-fed control groups and an ad libitum control group, fed with 50 mg iron/kg diet. The iron-depleted rats were classified as iron-deficient on the basis of reduced serum iron, hemoglobin concentration, and hematocrit. All moderately iron-deficient rats had significantly lower cholesterol concentrations in liver and serum lipoproteins than their pair-fed controls. Rats with the lowest dietary iron supply had higher concentrations of hepatic phosphatidylcholine (PC) and phosphatidylethanolamine (PE), lower activities of glucose-6-phosphate dehydrogenase, malic enzyme and fatty acid synthase, and higher triacylglycerol concentrations in serum lipoproteins than the corresponding pair-fed control rats. Moderate iron deficiency also depressed the serum phospholipid level. Moreover, several consistent significant differences in fatty acid composition of hepatic PC and PE occurred within moderate iron deficiency, which indicate impaired desaturation by Δ-9 and Δ-6 desaturases of saturated and essential fatty acids. We conclude that lipid variables, including cholesterol in liver and serum lipoproteins as well as fatty acid desaturation, reflect the gradations of iron status best and can be used as an indicator of the degree of moderate iron deficiency.     

Lipogenesis in iron-deficient adult rats

Iron-deficient (5 ppm Fe) or control (307 ppm Fe) diets were fed ad libitum to female rats for 7 weeks, and then meal-fed for 4 weeks. Body weights, hemoglobin levels, and hematocrits were lower (p<0.01) in deficient group (184±7, 7.1±0.4, 32.7±0.6) than in the control group (220±10, 16.9±0.3, 51.8±0.8) at the end of the 11-week experiment. Animals were killed 1 hr after meal feeding, and liver slices, mesenteric adipose tissue, and segments of mid-jejunum were incubated in vitro with [U-¹⁴C] glucose or³H₂O. Adipose tissue from deficient rats had incorporation of [U-¹⁴C] glucose into triglycerides two to three times greater than control rats (p<0.01). Release of¹⁴CO₂ from glucose was greater in adipose tissue of deficient rats than controls (p<0.05). Incorporation of³H₂O into triglycerides was also two to three times greater in deficient adipose tissue than in controls (p<0.02). In liver slices, incorporation of glucose in polar lipids was slightly higher in deficient rats than in control rats (p<0.05). No significant differences were found in incorporation of³H₂O or [U-¹⁴C] glucose into lipids or CO₂ in jejunum. Thus, iron- deficient adult rats have greater lipid synthesis from³H₂O and glucose in adipose tissue than rats fed adequate levels of iron.     

Alcohol ingestion and levels of hepatic fatty acid synthetase and stearoyl-CoA desaturase activities in rats

Male Sprague-Dawley rats were fed, ad libitum for 30 days, a fat-free (FF) liquid diet containing 34% of the calories as ethanol or a control FF diet in which alcohol was replaced by an isocaloric amount of dextrins. The cytosolic fatty acid synthetase and the microsomal stearoyl-CoA desaturase activities in the livers of rats fed the alcohol diet were about half of those observed in the livers of control rats. The conclusion is that chronic ethanol consumption depresses the activities of these lipogenic enzymes in the liver.     

Effect of antioxidants on lipid peroxidation in iron-loaded rats

Indirect evidence has suggested that lipid peroxidation is associated with iron overload in vivo. As a measure of lipid peroxidation, pentane expired in the breath of rats loaded with an accumulated dose of either 100 mg or 186–200 mg of iron injected intraperitoneally as iron dextran was measured over a 7 to 8 week period, and the effect on pentane production of feeding antioxidant-supplemented diets was determined. By the seventh week of feeding the diets, rats fed 0.3% L-ascorbic acid produced 17% less (P=0.03) pentane than did rats fed the basal antioxidant-deficient diet, whereas rats fed 0.004% dl-α-tocopherol acetate produced 92% less (P<0.001). After being fed the basal diet for 7 weeks, iron-loaded rats produced 76±9 pmol pentane/100 g body wt/min. When synthetic antioxidants were added to the diet at a concentration of 0.25%, the order of effectiveness in decreasing pentane production after 1 week was: N,N′-diphenyl-p-phenylenediamine > ethoxyquin > butylated hydroxyanisole > butylated hydroxytoluene > propyl gallate ∼ no antioxidant. After removal of either ethoxyquin or N,N′-diphenyl-p-phenylenediamine from the diets for 1 week, pentane production increased to a high level. The total amount of lipid soluble fluorophores in individual spleens of rats fed N,N′-diphenyl-p-phenylenediamine, ethoxyquin, dl-α-tocopherol acetate, ascorbic acid and no antioxidant were correlated significantly with the corresponding total integrated amount of pentane produced by the individual rats over the 7 to 8 week period. This study has provided some of the most direct evidence to date that lipid peroxidation is associated with iron overload in vivo.     

MCD Diet Rat Model Induces Alterations in Zinc and Iron during NAFLD Progression from Steatosis to Steatohepatitis

We evaluate the effects of the methionine-choline-deficient (MCD) diet on serum and hepatic zinc (Zn) and iron (Fe) and their relationships with matrix metalloproteinases (MMPs) and their modulators (TIMPs and RECK) as well as hepatic fatty acids using male Wistar rats fed 2-, 4- and 8-week MCD diets. Serum and hepatic Zn decrease after an 8-week MCD diet. Serum Fe increases after an 8-week MCD diet and the same occurs for hepatic Fe. An increase in hepatic MMP activity, associated with a decrease in RECK and TIMPs, is found in the MCD 8-week group. Liver Fe shows a positive correlation versus MMPs and RECK, and an inverse correlation versus TIMPs. A positive correlation is found comparing liver Zn with stearic, vaccenic and arachidonic acids, and an inverse correlation is found with linolenic and docosatetraenoic acids. An opposite trend is found between liver Fe versus these fatty acids. During NAFLD progression from steatosis to steatohepatitis, MCD rats exhibit an increase in Zn and a decrease in Fe levels both in serum and tissue associated with alterations in hepatic MMPs and their inhibitors, and fatty acids. The correlations detected between Zn and Fe versus extracellular matrix modulators and fatty acids support their potential role as therapeutic targets.     

Fatty acid patterns in iron-deficient maternal and neonatal rats

To determine the effects of maternal iron deficiency on lipid composition and fatty acid patterns in offspring, rats were fed ad libitum diets containing 5 ppm iron (deficient) (n=8) or 320 ppm iron (control) (n=7) and deionized water from day-1 of gestation through day-18 of lactation. On day-2 of lactation, litters were standardized to three male and three female pups. On day-18, pups were fasted for 4 hr before tissue and blood collection. Significant changes in serum and liver lipid concentrations and fatty acid patterns were observed in deficient pups. Serum triglycerides, cholesterol and phospholipids and liver triglycerides, cholesterol, and cholesteryl esters were increased. In deficient pups, percentage total fatty acids of 14∶0, 16∶1, 18∶1, 18∶2 from serum lipids were increased; in liver, 14∶0, 18∶2, 18∶3 were increased; 18∶0 and 20∶4 were decreased in both serum and liver. Dam serum lipid levels did not differ between groups. Lipid changes observed in iron-deficient pups did not consistently reflect the milk, serum or liver lipid patterns observed in dams. Altered lipid composition and fatty acid patterns of iron-deficient pups thus appear to be of endogenous origin.     

The effects of dietary protein on the fatty acid composition and Δ6 desaturase activity of rat hepatic microsomes

Recently, significant differences between rats fed a casein diet and rats fed a soybean protein diet have been observed in hepatic phospholipid fatty acid patterns (Sjöblom, L., and Eklund, A.,Biochim. Biophys. Acta 1004, 187–192, 1990). The influence of these two diets on the Δ6 desaturase activity was investigated in the present study because the hepatic desaturase system is a source of unsaturated fatty acids. The rats fed a casein diet showed higher desaturase activity than those fed soybean protein when using either linoleic acid (P<0.005) or oleic acid (P<0.05) as substrates. The phosphatidylcholine fraction of hepatic microsomes showed increases in oleic acid (P<0.005) and 20∶3ω9 (P<0.001) levels as well as decreases in stearic acid (P<0.001), linoleic acid (P<0.005) and arachidonic acid (P<0.005) levels in rats which were fed casein rather than soybean protein. Similar differences between the two groups were also observed in the phosphatidylethanolamine and phosphatidylinositol fractions. These data indicate that the qualitative properties of the dietary protein source may influence the fatty acid pattern of rat hepatic microsomes by interfering with Δ6 desaturase activity.     

Effects of deteriorated frying oil and dietary protein levels on liver microsomal enzymes in rats

This study was conducted to investigate the effects of deteriorated used frying oil (DUFO) and dietary protein levels upon the hepatic microsomal drugmetabolizing enzyme system. Fresh soybean oil was subjected to a deep-frying process at 205±5°C for four six-hr periods. The resultant DUFO was incorporated into high protein (HU) (27% lactalbumin) or low protein (LU) (8% lactalbumin) test diets at a 15% level. High protein (HF) and low protein (LF) diets containing fresh soybean oil served as the control. Male Long-Evans young rats fed the test diets for eight weeks showed decreased fat absorption and increased red blood cell (RBC) in vitro hemolysis. The activities of hepatic aminopyrine N-demethylase (AD), aniline hydroxylase (AH), NADPH-cytochrome C reductase (NCD), UDP-glucuronyl transferase (UDPGT) and glutathione S-transferase (GST) as well as cytochrome P-450 content were significantly increased in rats fed the HU diet. However, the AD, AH and GST activities, as well as the cytochrome P-450 content of the LU group, were increased to a lesser extent and significantly lower than those of the HU group. Rats fed the LU diet were the only group that showed significantly elevated serum GOT (E.C. 2.6.1.1, glutamate-oxaloacetate transaminase) and GPT (E.C. 2.6.1.2, glutamatepyruvate transaminase) values. Supplementation of 0.3% DL-methionine to the HU diet further increased GST activity. Unexpectedly, rats fed the low protein control diet (LF) also had raised levels of AD, AH and UDPGT activities as well as in vitro RBC hemolysis. It was concluded that rat hepatic microsomal enzymes are induced by dietary DUFO and that the level of induction is influenced by dietary protein level.     

Effects of dietary fats on fatty acid composition and Δ5 desaturase in normal and diabetic rats

We have studied the effect of various diets on the phospholipid fatty acid composition andin vitro Δ5 desaturase activity of hepatic microsomes derived either from the normal or streptozotocin-induced diabetic rat. The diets studied were the standard rat chow diet and a basal fat-free diet supplemented either with 20 percent saturated fat, 20 percent unsaturated fat, or 20 percent menhaden oil. Phospholipid fatty acid composition analysis revealed that the normal rat fed the saturated fat or menhaden oil diet had significantly decreased arachidonate levels, consistent with decreased Δ5 desaturase activities and decreased 18∶2n−6 intake. On the contrary, the unsaturated fat diet decreased dihomo-γ-linolenate and increased arachidonate levels, without increased Δ5 desaturase activity. Streptozotocininduced diabetes resulted in decreased arachidonate and Δ5 desaturase activity. The unsaturated fat diet fed to the diabetic rat also failed to correct this decreased Δ5 desaturase activity. The unsaturated fatty acids in this diet also displaced a substantial amount of n−3 fatty acids in both normal and diabetic microsomes, due to the competition between these two fatty acid families for incorporation into the membrane phospholipids. Conversely, the menhaden oil diet fed to the normal and diabetic rats displaced n−6 fatty acids, reduced Δ5 desaturase activity, and enhanced 22∶6n−3 incorporation into diabetic microsomes.