Microsomal Fatty Acid Composition Research Articles

Dietary saturated and monounsaturated fats protect against acute acetaminophen hepatotoxicity by altering fatty acid composition of liver microsomal membrane in rats

BackgroundDietary polyunsaturated fats increase liver injury in response to ethanol feeding. We evaluated the effect of dietary corn oil (CO), olive oil (OO), and beef tallow (BT) on fatty acid composition of liver microsomal membrane and acute acetaminophen hepatotoxicity.MethodsMale Sprague-Dawley rats were fed 15% (wt/wt) CO, OO or BT for 6 weeks. After treatment with acetaminophen (600 mg/kg), samples of plasma and liver were taken for analyses of the fatty acid composition and toxicity.ResultsTreatment with acetaminophen significantly elevated levels of plasma GOT and GPT as well as hepatic TBARS but reduced hepatic GSH levels in CO compared to OO and BT groups. Acetaminophen significantly induced protein expression of cytochrome P450 2E1 in the CO group. In comparison with the CO diet, lower levels of linoleic acid, higher levels of oleic acids and therefore much lower ratios of linoleic to oleic acid were detected in rats fed OO and BT diets.ConclusionsDietary OO and BT produces similar liver microsomal fatty acid composition and may account for less severe liver injury after acetaminophen treatment compared to animals fed diets with CO rich in linoleic acid. These findings imply that types of dietary fat may be important in the nutritional management of drug-induced hepatotoxicity.

Influence of dietary cholesterol and stress on the metabolism of linoleic acid: Δ6-desaturase activity vs. product/precursor ratios

Δ6-desaturase is a membrane bound enzyme located in a pivotal position within the Essential Fatty Acid metabolic pathway. Changes in the activity of Δ6-desaturase affect the cellular provision of long chain polyunsaturated fatty acids and therefore factors that influence this enzyme are considered relevant to disease processes. This study investigated the effects of social isolation stress and cholesterol supplementation in a rodent model using two methods to estimate Δ6-desaturase activity, namely, a direct method measuring liver microsomal Δ6-desaturase activity and an indirect method measuring product–precursor ratio from tissue fatty acid compositions. Liver Δ6-desaturase activity was significantly decreased by isolation (-14%) and increased by cholesterol feeding (+9%). Liver microsomal phospholipid fatty acid composition and the associated product–precursor ratios for Δ6-desaturase did not relate to the changes observed in Δ6 desaturase activity. These results indicate that tissue fatty acid compositions should be viewed with caution in terms of their appropriateness as a surrogate for measuring Δ6-desaturase activity.

Effects of streptozotocin and dietary fructose on delta-6 desaturation in spontaneously hypertensive rat liver

We have investigated the effects of hypertension associated with diabetes mellitus on polyunsaturated fatty acid biosynthesis. For this purpose, two rat models for these pathologies have been established: a type 1 diabetic hypertensive model obtained by streptozotocin injection to spontaneously hypertensive rat (SHR), followed or not by insulin treatment (experiment 1); a type 2 diabetic hypertensive model by feeding SHR with a fructose enriched diet (experiment 2). Liver gene expression of delta-6 desaturase (D6D), microsomal D6D activities and fatty acid composition of total lipids were estimated. In experiment 1, an increase of linoleic acid (18:2 n-6) level was observed in the streptozotocin group. D6D gene expression appeared depressed in both experimental groups. Insulin did not reverse the streptozotocin effect in SHR, as it does in insulin-dependent diabetic rats. In experiment 2, the results showed a decrease of 18:2 n-6 and of long chain products of desaturation in rats fed on fructose diet. Delta-6 n-3 desaturase activity was significantly increased, whereas gene expression tended to decrease. Feeding fructose induced a significant increase in delta-9 desaturated products, suggesting a stimulation of stearoyl-CoA desaturase. These changes in monounsaturated fatty acids strongly differ from those observed in the streptozotocin experiment, indicating that the effects on lipogenesis of hypertension linked to diabetes differ according to the type of diabetes. Then, these results indicate that the liver steatosis observed during genetic hypertension was reinforced by fructose feeding. All together, the present results showed that hypertension associated to type 1 or type 2 diabetes exacerbated the damage caused by diabetes or hypertension alone on liver lipid metabolism. The metabolic effects induced by fructose being very similar to those found in human NIDDM, SHR fed a fructose-rich diet appears to be an appropriate model for studying the consequences of the combination of hypertension and NIDDM in the metabolic syndrome diseases.

In vivo modification of the UDP-glucuronosyltransferase functional state in rat liver following hypophysectomy and partial or complete hormonal restoration.

The effects of growth hormone on the uridine diphosphate glucuronosyltransferase functional state, biophysical membrane parameters (order parameters and rotational correlation frequency) and the composition in phospholipids were studied in male rat hepatic microsomes. Sham-operated and hypophysectomized animals were injected with two different dosages of growth hormone, mimicking either the male or female growth hormone secretion pattern. Half the animals received thyroxine and cortisol in concentrations chosen to compensate for the lack of thyroid hormones and glucocorticoids in hypophysectomized rats. Growth hormone treatment resulted in a decrease in the latency (that gives a quantification of uridine diphosphate glucuronosyltransferase functional state) of the glucuronidation activities towards various substrates (testosterone, androsterone, bilirubin and 4-nitrophenol). This decrease with growth hormone treatment was particularly evident in hypophysectomized animals that had received cortisol and thyroxine supplementation treatment. These modifications were strongly correlated with modifications in the microsomal membrane lysophospholipid content and to a lower extent with microsomal membrane fatty acid composition. The cytosolic phospholipase A(2)-dependent increase in the lysophospholipid content in the endoplasmic reticulum is probably a major determinant in the regulation of the functional state of glucuronoyltransferases in response to high dosage growth hormone treatment.

Effect of the Degree of Hydrogenation of Fish Oil on the Enzymatic Activity and on the Fatty Acid Composition of Hepatic Microsomes from Young and Aged Rats

By modifying the degree of hydrogenation of dietary fat, it is possible to modify the fatty acid composition and the biochemical activity of cellular tissues. The age can be another variable influencing these modifications. The effect of isocaloric diets containing oils with different degrees of hydrogenation: fish oil (FO, 0.3% trans), partially hydrogenated fish oil (PHFO, 29% trans), or highly hydrogenated fish oil (HHFO, 2.3% trans), in the fatty acid composition (cis and trans isomers) of hepatic microsomes from young (70-day-old) and aged (18-month-old) rats, in the microsomal cytochrome P-450 (C-450) content, and in the aminopyrine N-demethylase (AND), aniline hydroxylase (AH), NADPH cytochrome P-450 reductase (NCR), UDP-glucuronyl transferase (UGT), and GSH-S transferase (GST) enzymatic activities were studied. Fatty acid composition and n–6/n–3 ratio of microsomal membranes was modified to a higher extent in young rats. C-450 content and AND activity were reduced when the degree of hydrogenation of dietary fat was increased in the young and the aged rats. AH activity was higher after the PHFO diet in the young rats only. NCR activity was reduced in the young animals when the hydrogenation of the fat was increased. However, in aged rats the enzyme exhibited a higher activity after the PHFO and HHFO diet. UGT and GST activities where not affected by the level of hydrogenation of the dietary fat in both the young and the aged rats. However, UGT activity was higher in the young rats, while GST activity was higher in the aged animals. We conclude that hydrogenation of dietary fat can modify the fatty acid composition of hepatic microsomes, young animals being more sensitive to these changes than aged animals. These effects were also reflected in the amount and/or the activity of some molecular components of the hepatic microsomal mixed-function oxidase enzyme system. Microsomal trans fatty acid composition is not affecting the activity of the enzymes, the age of the animals being the most important factor

Fatty acid desaturase activities and polyunsaturated fatty acid composition in human liver between the seventeenth and thirty-sixth gestational weeks

Objective: The aim of the study was to characterize n-3 and n-6 fatty acid Δ5- and Δ6-desaturase activities and their time course variations in human fetal liver between the 17th and 36th gestational week. Study Design: Twenty-one biologic samples were obtained after legally approved medical abortion, according to French law. The desaturase activities were measured in the 21 liver samples by a radiochemical method by means of reverse-phase high-performance liquid chromatography. The fatty acid composition (percentage by weight) of liver phospholipids was assessed in 16 samples by gas-liquid chromatographic analysis. Results: Both Δ5- and Δ6-desaturase activities were significantly expressed between the 17th and 36th gestational weeks. During the second trimester n-6 fatty acid Δ5- and Δ6-desaturase activities showed opposite patterns of variation; both then remained stable between the 25th and 36th weeks. Δ6-Desaturation was higher in n-3 than n-6 fatty acids and peaked at the 18th gestational week. The percentages of linoleic and docosahexaenoic acids in liver microsomes were positively correlated with the gestation age (P < .01), whereas arachidonic acid remained stable. Conclusion: Significant n-3 and n-6 Δ5- and Δ6-desaturase activities are expressed in human fetal liver as early as the 17th gestational week and are stable throughout the third trimester. Their theoretic capacity evaluated from in vitro measurements appears lower than polyunsaturated fatty acid requirements and is not directly related to liver microsomal membrane fatty acid composition. (Am J Obstet Gynecol 1998;179:1063-70.)

Effects of food restriction on antioxidant defense system in exercised rats

The present study was designed to investigate the effects of food restriction on the activities of hepatic antioxidant enzymes in exercised male Fischer-344 rats. Weanling male Fischer-344 rats were fed semipurified diet containing 10% corn oil diet (CO), or lab chow (LC), ad libitum (AL) and at 40% food restriction (FR). After being on the diets for two months, the animals in each diet group was divided into sedentary (S) and exercised (EX) groups. The diets were continued and the animals in the exercise group were run everyday for two months on tread mill to exhaustion. The three key enzymes involved in the antioxidant defense system were determined in the hepatic cytosolic fraction. Catalase activity was significantly higher in the livers of rats fed restricted diets when compared to AL fed rats with the exception of the LC-EX group. Superoxide dismutase (SOD) activity in the CO diet fed groups was significantly lower compared to rats fed the LC diet. Exercise significantly increased SOD activity only in the LC-AL group. In the CO-AL group, SOD activity in exercised rats decreased significantly compared to those from the sedentary group. Exercise resulted in modest increase in the glutathione peroxidase (GSH-Px) activity in these food restricted groups. The LC diet groups had significantly higher levels of saturates (16:0 and 18:0) and monounsaturated fatty acids and significantly lower levels of 18:2n-6, 18:3n-3, 20:3n-3, 20:4n-6, 20:5n-3, 22:5n-3 and 22:6n-3 compared to the CO-fed groups in the liver microsomes. Lipid peroxidation in the liver microsomes of CO fed rats was significantly higher compared to that of LC-AL-S group. The data from the present study suggest that food restriction and exercise have differential effects on the enzymes involved in antioxidant defense and the microsomal fatty acid composition was not altered by exercise or food restriction. Moreover, exercise did not increase lipid peroxidation in these rats.

Effect of extensive feeding on α-tocopherol concentration and oxidative stability of muscle microsomes from Iberian pigs

AbstractThe effect of extensive feeding, confinement and diet supplementation with a-tocopheryl acetate (100 mg/kg) on the fatty acid composition and tocopherol concentration of microsome extracts and their susceptibility to oxidation was studied in Iberian pigs. The diet of pigs raised extensively was mostly composed of acorn and grass. The a-tocopherol contents of acorn and grass were 20 and 171 mg/kg dry matter, respectively. Microsomal fatty acid composition showed no differences among groups. Pigs feeding extensively had a higher concentration of a-tocopherol in muscle and microsomes than pigs given mixed diet with the basal level of a-tocopheryl acetate (P &lt; 0·05) but lower values than pigs given supplementary levels (100 mg/kg) (P &lt; 0·05). Microsomal fractions from pigs given mixed diet with a basal level of a-tocopheryl acetate were significantly more susceptible to iron-induced lipid oxidation than extract from pigs given diets containing a supplementary level (P &lt; 0·05). Microsomal extracts from pigs feeding extensively had the lowest oxidation rate (P &lt; 0·05), suggesting that other dietary constituents may play a role in the stabilization of microsomal lipids.

Hepatic microsomal membrane lipidic composition and growth hormone effect in adult male rat: evidence for a `feminization' process of total phospholipid fatty acid pattern

Growth hormone (GH) effects on fatty acid composition and on Δ 5-, Δ 6-, Δ 9-desaturase and palmitic acid elongation activities were studied in male rat hepatic microsomes. Sham-operated and hypophysectomized animals were injected with two different dosages of GH, mimicking either the male or female GH secretion pattern. Half the hypophysectomized animals received thyroxine and cortisol in concentrations chosen to compensate for the lack of thyroid hormones and glucocorticoids. GH, administered to sham-operated or to cortisol/thyroxine-treated hypophysectomized rats resulted in an increase in stearic and arachidonic acid proportions, while palmitic acid percentage was decreased. Total monounsaturated fatty acids were dramatically reduced by this treatment. Δ 5-Desaturase and palmitic acid elongation activities were increased by GH treatment, while Δ 9-desaturase activity was decreased. These GH effects on desaturation and elongation activities could explain the modifications in microsomal fatty acid composition. Hypophysectomy markedly altered the fatty acid composition by reducing arachidonic and stearic acid proportions and increasing the linoleic acid proportion, while Δ 9-, Δ 5-desaturase and palmitic acid elongation activities were decreased. Restoration of most of the fatty acid proportions to control values was realized in hypophysectomized animals with a cortisol/thyroxine replacement administered alone or together with the low dosage of GH mimicking the male secretion pattern. High GH dosage produces essentially a `feminization' process of the fatty acid composition of the hepatic microsomal membrane in male rats when compared to that of females.

The effect of a formula supplemented with n-3 and n-6 long-chain polyunsaturated fatty acids on plasma phospholipid, liver microsomal, retinal, and brain fatty acid composition in neonatal piglets

We explore in this study the influence of dietary (n-6) and (n-3) long-chain polyunsaturated fatty acids (LC-PUFA) on tissues fatty acid composition in early life. Eight newborn piglets were fed sow milk for 20 days (group SM, n = 8); another sixteen newborn piglets were initially fed an adapted pig milk formula for 3 days and then assigned to receive for 17 days either the same adapted formula (group F, n = 8), or a formula supplemented with a phospholipid source of (n-6) and (n-3) LC-PUFA (group P, n = 8). Plasma phospholipid and liver microsomes 16:1(n-7) and 18:1(n-7) were increased in animals fed maternal milk compared with those fed formulas. Feeding the LC-PUFA formula produced significantly high plasma phospholipid and liver microsomal 22:6(n-3) than feeding the control formula. Similar plasma phospholipid and liver microsomal (n-6) and (n-3) LC-PUFA were found in animals fed SM and in those fed the control formula. The supplementation of LC-PUFA did not lead to any change in brain and retinal 20:4(n-6) and 22:6(n-3). No differences were found in brain and retinal 22:6(n-3) between animals fed the formula devoid of LC-PUFA and those fed sow milk. Retinal 22:4(n-6), 22:5(n-6) and 22:5(n-3) contents were significantly higher in maternal milk fed animals as compared with control formula fed animals. In brain, animals fed sow milk had higher (n-6) LC-PUFA than animals fed the supplemented formula. The results obtained in this study indicate that the supplementation of a phospholipid source of LC-PUFA influences plasma and liver microsomes 22:6(n-3). Under these experimental conditions, brain and retinal 22:6(n-3) were insensitive to the dietary supplementation.

Effect of dietary lipids on activities of hepatic steroid metabolizing enzymes (5α-reductase and aromatase) and composition of microsomes

The effects of dietary fat (saturated, ω-6 and ω-3 fatty acids) on the activities of two key steroid metabolizing enzymes, 5α-reductase and aromatase, were examined in the present study. These enzymes are widely speculated to be involved in the initiation of prostate and breast cancer. Weanling male Sprague Dawley rats were fed semi-purified diets containing 14% fat of either beef fat (BF), safflower oil (SO) or fish oil (FO) for 7 wks and enzyme activity and hepatic microsomal phospholipid fatty acid composition were analyzed. 5α-reductase and aromatase activities were differentially modulated by the dietary lipids. Animals fed the FO diet showed significantly higher 5α-reductase activity compared to those fed the BF diet. Rats fed the SO diet had the highest activity of microsomal aromatase compared to animals fed the BF or FO diet. Liver microsomal lipids of animals fed the BF diet had a higher percentage of saturated (stearic, 18:0) and monounsaturated (oleic, 18:1) fatty acids compared to those of SO and FO fed groups while microsomes of animals fed BF and SO diets contained higher percentages of ω-6 fatty acids compared with FO diet group. Feeding FO diet resulted in accumulation of significantly higher levels of ω-3 fatty acids (20:5, 22:5 and 22:6) in the microsomes compared to the BF or SO fed groups. The data suggest that dietary fatty acids may play a role in steroid hormone action through modulating the activities of these two steroid metabolizing enzymes.

Chronic Administration of Ursodeoxycholic and Tauroursodeoxycholic Acid Changes Microsomal Membrane Lipid Content and Fatty Acid Composition in Rats

We studied the effect of oral supplementation with ursodeoxycholate (UDCA) or tauroursodeoxycholate (TUDCA) on the lipid content and fatty acid composition of rat hepatic microsomes. UDCA and TUDCA significantly increased the total amount of lipids with the exception of cholesteryl-esters. UDCA significantly increased the triglycerides and phosphatidylethanolamine (PE) microsomal content, and decreased the cholesterol/phospholipids and the phosphatidylcholine (PC)/PE ratio. Both treatments increased the percentage of oleic acid and of polyunsaturated fatty acids (PUFA) in each class of lipids. UDCA and TUDCA had a different action on PUFA microsomal molar percentage of phospholipids: UDCA increased the relative percentage of PUFA in the PE fraction, while TUDCA increased the relative percentage of PUFA in the PC fraction. These changes in the hepatic lipid content and composition might in part explain both cytoprotective action of these hydrophillic bile acids and their effect on membrane fluidity.

Gender-related differences in the amount and functional state of rat liver UDP-glucuronosyltransferase

The basis for gender-dependent differences in rates of glucuronidation of xenobiotics is uncertain. To clarify this issue, the glucuronidation of p-nitrophenol was compared in liver microsomes from adult male and female rats. The activity of native UDP-glucuronosyltransferase was 47% higher in microsomes from male than from female rats. Immunoblotting of microsomal protein with anti-UDP-glucuronosyltransferase antiserum revealed 66% more immunoreactive protein in male microsomes. A kinetic method for measuring glucuronidating enzyme content confirmed the result of the immunoblot. Responses of UDP-glucuronosyltransferase to activation by palmitoyllysophosphatidylcholine or high pressure indicated that the activity of the enzyme was more latent in male than in female microsomes. Differences in enzyme latency could be due to differences in membrane structure. A comparison of microsomal fatty acid composition revealed significantly higher levels of oleic and linoleic acids and lower levels of stearic and docosahexaenoic acids in male than in female microsomes. The phospholipid composition, ratio of cholesterol: phospholipid, and membrane fluidity were similar in male and female microsomes. These results indicate that gender-dependent differences in UDP-glucuronosyltransferase activity are due to differences in both the amount and functional state of the enzyme.

Liver microsomal fatty acid composition in ethanol-fed rats: effect of different dietary fats and relationship to liver injury.

The rat intragastric feeding model for alcoholic liver disease was used to study the effect of different diets on the fatty acid composition of liver microsomes. Rats were fed corn oil and ethanol (CE), saturated fat and ethanol (SF+E) or corn oil and dextrose (CD) for either 2 or 4 weeks. Rats were also fed saturated and dextrose (SF+D) for 4 weeks. In comparison with the CD diet, lower levels of arachidonic acid were detected in rats fed the CE, SF+E, and SF+D diets. However, the diet-induced changes in levels of arachidonic acid varied as a function of length of feeding. In rats fed the CE diet, we detected a significant decrease in the level of arachidonic acid compared with CD animals. Conversely, in rats fed the SF+E diet, the level of arachidonic acid increased compared with the SF+D group. In addition, a significant correlation was noted between levels of oleic acid and arachidonic acid in both corn oil (r = -0.85, p < 0.01) and saturated fat (r = -0.76, p < 0.05) groups. However, the changes in levels of arachidonic acid and oleic acid were in opposite directions in the two groups. Levels of docosahexaenoic acid decreased between the 2 and 4 weeks in animals maintained on the CE diet. Levels of stearic acid increased between 2 and 4 weeks in rats fed the SF+E diet. The lowest level of linoleic acid was detected in the SF+D and SF+E groups, but levels of linoleic acid remained constant in all groups throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Developmental changes in cholinephosphate cytidylyltransferase activity and microsomal phospholipid fatty acid composition in alveolar type II cells

Cholinephosphate cytidylyltransferase is the rate-limiting enzyme in the choline pathway of phosphatidylcholine synthesis in fetal and adult lung. To examine the developmental changes in cytidylyltransferase activity, subcellular fractions were prepared from freshly isolated type II cells from 19 and 21 d gestation fetal rats, newborn (0 h, 3 h, 3–12 h, +1, +2, +7 postnatal day), and adult rats and the fractions assayed for cytidylyltransferase activity. Cytidylyltransferase activity per cell was low during late fetal gestation, but rose rapidly during the first 3 h after birth, predominantly due to an increase in microsomal enzyme activity. Microsomal and cytosolic enzyme specific activity increased 6 and 3.9 fold, respectively, from birth (0 h) to +1 postnatal day. The subcellular distribution of enzyme activity changed from 40% microsomal in fetal type II cells to 85% microsomal at 3–12 h, and 60% in this compartment in adult type II cells. Although evidence suggests that membrane lipid may affect enzyme activity, developmental changes in type II cell membrane phospholipid fatty acid composition have not been previously studied. Capillary gas chromatography analysis of phospholipid fatty acids extracted from microsome fractions revealed a 3-fold increase in both total saturated and unsaturated phospholipid fatty acids from day 19 to day 21 gestation. There was a further 62% increase in total saturated fatty acids during the first postnatal day, concomitant with the peak in microsomal cytidylyltransferase activity.

Adrenic acid Δ4 desaturation and fatty acid composition in liver microsomes of spontaneously diabetic Wistar BB rats

We examined the Δ4 (n-6) desaturation and the fatty acid composition of liver microsomes in the insulin-dependent spontaneously diabetic Wistar Bio-Breeding (BB) rat. The desaturation of adrenic acid to n-6 docosapentaenoic acid was decreased in the normo- and hyperglycemic diabetic rats. Insulin treatment with 1.0 IU. 100 g body weight −1 twice a day for 2 days restored the reduced activity during the hypoglycemic period. The pattern of responses was similar to that of linoleic acid Δ6 and dihomo-γ-linolenic acid Δ5 desaturases, with a non-parallel relationship between the desaturation system and the glycemia. The microsomal fatty acid composition of BB rat liver reflected only partially to the Δ4 desaturation at different states of glycemia. Factors other than impaired desaturation system are involved in the fatty acid metabolism of spontaneously diabetic rats.

Effect of L-triiodothyronine on liver microsomal delta 6 and delta 5 desaturase activity of male rats.

The effect of different doses of L-triiodothyronine (T3) on the activity of delta 6 and delta 5 desaturases and lipid fatty acid composition was studied in liver microsomes of male rats. The activity of delta 6 and delta 5 desaturases was decreased 24 and 28%, respectively, in animals administered a daily intraperitoneal dose of 1000 micrograms T3/100 g body wt. for 5 days, whereas with 500 micrograms T3/100 g body wt. only delta 6 desaturase activity was decreased. On the other hand, no enzyme activity changed at a shorter period of hormone treatment. Changes in microsomal fatty acid composition did not seem to be a direct consequence of desaturation activity, since after 1 and 5 days of T3 treatment, the concentrations of 18:2 (n-6) and 20:3 (n-6) decreased and only after 1 day that of 20:4 (n-6) increased in spite of unchanged or decreased delta 6 and delta 5 desaturase activities. Other factors than desaturation activity must be involved in fatty acid composition of thyroid hormone-treated rats, such as diet, membrane lipid synthesis and degradation, fatty acid turn-over and oxidation.

Altered desaturase activities and fatty acid composition in liver microsomes of spontaneously diabetic Wistar BB rat

We examined the activities of Δ9, Δ6 and Δ5 desaturases and fatty acid composition of liver microsomes in the insulin-dependent spontaneously diabetic adult female Wistar Bio-Breeding (BB) rat. The diabetic BB rats were subcutaneously injected with different doses of protamine zinc insulin in order to be killed in hyper-, normo- or hypo-glycemic states. Desaturase activities, which are partially inhibited by spontaneous diabetes during the normo-and hyper-glycemic periods, were similarly affected by the various insulin treatment; Δ9 desaturase activity being more depressed than the desaturase activities of either Δ6 of Δ5. Insulin treatment with 10 I.U./kg body weight twice a day for 2 days was able to restore the Δ9, Δ6 and Δ5 desaturase activities to control levels during the hypoglycemie period. The microsomal fatty acid composition of BB rats liver was not consistent with the desaturase activities, particularly Δ9 desaturase activity, during the different states of glycemia, indicating that they are not closely linked in a direct cause-effect relationship.

Changes in microsomal phospholipid fatty acids composition in cholestatic rats.

In the rat, the effect of the bile duct ligation on liver microsomal phospholipid fatty acid composition and on phosphatidylcholine, phosphatidylserine and phosphatidylinositol pattern were studied. After two days of cholestasis, microsomal phospholipid fatty acids showed a decrease in linoleic, stearic and arachidonic acids and an increase in oleic and docosahexaenoic ones, as compared to controls. Phosphatidylcholine showed an increment in oleic and palmitic acid content and a concomitant decrease in arachidonic acid. Phosphatidylserine showed a progressive increase while phosphatidylinositol showed a progressive decrease in all fatty acids. Eight-days post-cholestatic rats showed a marked increase in oleic acid, whereas linoleic, arachidonic, stearic and palmitic acids concentration decreased. Phosphatidylcholine showed a global decrease in its fatty acid content, except for oleic which is increased. Phosphatidylserine showed an increase over the two-days cholestasis fatty acids values. Phosphatidylinositol decreased in most fatty acids except in docosahexaenoic acid that recovered normal values. It was concluded that cholestasis produced significative changes in the fatty acid composition of the major phospholipids constituents of the microsomal membranes.

Effect of dietary fat on diabetes-induced changes in liver microsomal fatty acid composition and glucose-6-phosphatase activity in rats.

Experimental diabetes may manifest itself in a defect in liver microsomal fatty acid desaturation and increased activity of glucose-6-phosphatase (G-6-Pase). The present study was designed to determine whether these changes could be normalized by a change in the dietary fat consumed. Control and streptozotocin-induced diabetic rats were fed nutritionally adequate diets which varied in fatty acid composition. Fatty acid analysis of liver microsomal phospholipids revealed that non-diabetic control animals fed saturated fat (beef tallow) or a diet high in omega 3 fatty acids (fish oil) exhibited a significantly higher level of 18:2 omega 6 and a lower level of 20:4 omega 6 in the phosphatidylcholine and phosphatidylethanolamine fractions compared with diabetic animals. Control and diabetic animals fed the high linoleic acid diet had similar levels of 18:2 omega 6 in the microsomal phosphatidylcholine and phosphatidylserine fractions. Microsomal G-6-Pase activity was higher in diabetic than in control animals. Activity of G-6-Pase was lower in microsomes of control animals fed the soybean oil or the fish oil diet, but was not significantly reduced in diabetic animals fed high polyunsaturated fats. Blood glucose levels were similar in control groups fed the different diets, but the plasma hemoglobin Alc level was lower in diabetic animals fed the soybean oil diet. Cholesterol and triglyceride levels were lower in diabetic animals fed the fish oil-based diet. The results suggest that dietary fat manipulation has the potential to change at least some of the abnormalities in the microsomal membrane in experimental diabetes.