Dietary fish oil enhances insulin sensitivity in miniature pigs

The effects of dietary fish oil, MaxEPA, and corn oil on insulin sensitivity were examined in male miniature pigs. The pigs (20-35 kg) received 750 g of nonpurified diet per day (160 g/kg protein, 50 g/kg fat) with the addition of either 30 g corn oil or 30 g MaxEPA, resulting in 90 g total fat per kg diet for 4-5 wk. The MaxEPA diet provided 12.6 g (n-3) polyunsaturated fatty acids per kg diet (6.7 g eicosapentaenoic acid, 4.8 g docosahexaenoic acid), 4.7 g (n-3) polyunsaturated fatty acids and 147 mg cholesterol. The corn oil diet provided 22.7 g (n-6) polyunsaturated fatty acids per kg diet and no (n-3) polyunsaturated fatty acids; cholesterol was added to equal the amount in the MaxEPA. After overnight withdrawal of food, intravenous glucose tolerance tests were conducted in conscious pigs by using previously placed jugular vein catheters. Plasma glucose responses and the areas under the plasma glucose curves were similar in seven MaxEPA- and five corn oil-fed pigs. However, the incremental areas under the insulin curves were significantly lower for the pigs fed MaxEPA. Thus values for insulin sensitivity (SI), determined with Bergman's minimal model, were significantly higher for MaxEPA than for corn oil-fed pigs, whereas the rate of glucose disappearance (KG), did not differ between the two groups. Therefore, substitution of (n-3) for (n-6) polyunsaturated fatty acids in dietary lipids is associated with enhanced insulin sensitivity in male pigs.     

Effects of dietary fatty acids on eicosanoid-generating capacity, fatty acid composition and chemotactic activity of rainbow trout (Oncorhynchus mykiss) leucocytes

Rainbow trout, Oncorhynchus mykiss, were maintained on isocalorific diets in which either sunflower, menhaden or Fosol oils were used as the dietary source of fatty acids. At intervals over a period of 6 months, head kidney leucocytes were isolated and used for the analysis of their fatty acid composition and eicosanoid-generating capacity. Major changes in fatty acid composition were apparent within 4 weeks on the diets, with fish fed sunflower oil diets showing a 2.1-fold increase in total n-6 fatty acids and a 2.3-fold decrease in n-3 fatty acids, compared with the original basal levels. By week 8 the fatty acid composition changes were greater in the sunflower-fed fish, but thereafter remained relatively stable to the end of the experiment at week 24. Leucocytes from the fish maintained for > 8 weeks on the sunflower oil containing diet produced significantly lower percentages of 5-series lipoxygenase products derived from eicosapentaenoic acid including 12-hydroxyeicosapentaenoic acid, leukotriene B5 and lipoxin A5 compared with those cells from fish fed either menhaden or Fosol based diets. Unlike the fatty acid composition, differences in lipoxygenase product profiles between the dietary groups increased throughout the experiment and by week 24 the arachidonic acid/eicosapentaenoic acid derived product ratios were approx. 14:1 in the sunflower oil-fed fish compared with approx. 1:1.5 in the menhaden oil-fed fish. A functional consequence of these differing ratios was seen in the ability of supernatants containing these products to cause the in vitro locomotion of trout neutrophils. Supernatants from sunflower oil-fed fish were less chemo-attractive than supernatants from menhaden or Fosol oil-fed fish.     

Low levels of eicosapentaenoic and docosahexaenoic acids mimic the effects of fish oil upon rat lymphocytes

Fish oil is rich in the long chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); typically these fatty acids constitute 20 to 25 g/100 g total fatty acids in fish oil. Feeding rodents diets rich in fish oil has been shown to decrease lymphocyte proliferation and natural killer cell activity. It is not known what level of EPA + DHA is required in the diet to exert these effects. This question was addressed in the current study. Weanling rats were fed on high fat (178 g/kg) diets which contained 4.4 g alpha-linolenic acid (control) or 4.4 g EPA + DHA (4.4 EPA + DHA) or 6.6 g EPA + DHA (6.6 EPA + DHA)/100 g total fatty acids. The n-6 to n-3 polyunsaturated fatty acid ratio was maintained at approximately 7. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Spleen lymphocyte proliferation in response to concanavalin A, spleen natural killer cell activity and PGE2 production by spleen leukocytes were reduced by feeding the EPA + DHA diets compared with feeding the control diet; the 4.4 and 6.6 EPA + DHA diets caused very similar reductions. The 4.4 EPA + DHA diet reduced popliteal lymph node weight following a localised graft versus host response; this response was not investigated in rats fed the 6.6 EPA + DHA diet. The reductions in lymphocyte functions and in the in vivo graft versus host response caused by the EPA + DHA diets were similar to those previously reported following the feeding of diets rich in fish oil. Thus, this study shows that diets containing relatively low levels of EPA + DHA (20 to 25% of the level found in fish oil) exert immunomodulatory effects. Furthermore, this study suggests that the maximal effect of EPA + DHA is exerted when these fatty acids constitute a level of less than or equal to 4.4 g/100 g total dietary fatty acids.     

Loss of substance of the lateral region of the face

The cardiovascular effects of a partially purified extract of fish oil, enriched in the n-3 series fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were studied in stroke-prone spontaneously hypertensive rats (SHR-SP) fed with high- and low-sodium diets during 5 weeks. Addition of salt to the low-salt control diet at a level commonly found in human food items (6% NaCl of the dry weight of the diet) produced a remarkable rise in blood pressure, an increase in left ventricular weight-to-body weight ratio (LVH-index) and an increase in kidney weight-to-body weight ratio (RH-index). Fish oil (20% of the dry weight of the diet) did not significantly influence the blood pressure or LVH-index or RH-index during the low-salt control diet. However, fish oil completely prevented the remarkable rise in blood pressure and clearly antagonized the rise of both LVH- and RH-indices, induced by the high-salt diet. The fish oil supplementation increased the levels of the polyunsaturated fatty acids of the n-3 series and decreased those of the n-6 series in plasma and kidney, irrespective of the salt content of the diet. Fish oil lowered serum thromboxane B2 concentration by approximately 75%. During the high-salt diet, fish oil markedly decreased water intake and urine volume, and increased urinary sodium concentration by about 60%. Our findings show that, in addition to an antihypertensive effect, fish oil also decreases LVH and RH. These effects appear to be due to an improved ability to excrete sodium and could be explained by the observed changes in the fatty acid composition and metabolism.     

Simultaneous measurement of [18F]FDOPA metabolism and cerebral blood flow in newborn piglets

Three diets containing either borage oil (BO) and southern hemisphere fish oil Marinol (MO), or BO and tuna orbital oil (TO), or a northern hemisphere fish oil (FO) were fed to duplicate groups of turbot (Scophthalmus maximus) of initial mean weight 1.2 g for a period of 12 weeks. The BO/MO and BO/TO diets were enriched in gamma-linolenic (18:3n-6, GLA) and eicosapentaenoic (20:5n-3, EPA) acids, and GLA and docosahexaenoic acid (22:6n-3, DHA), respectively. No differences were observed in final weights or growth rates, either between duplicate tanks or between dietary treatments. Half of the FO-fed fish sampled showed a histopathological lesion indicative of lipoid liver degeneration while the other treatments only showed a slight incidence of the same pathology. The fatty acid compositions of carcass and tissues broadly reflected the dietary input. In general, fish fed the BO/MO diet had increased levels of 18:2n-6, 18:3n-6, 20:3n-6 and 20:5n-3, but a lower level of 22:6n-3, compared to fish fed FO. In fish fed the BO/TO diet, levels of 18:2n-6, 18:3n-6, 20:3n-6 and 20:4n-6 were increased while levels of 20:5n-3 and 22:5n-3 were reduced, compared to fish fed FO. Concentrations of thromboxanes B (TXB) and leukotrienes B (LTB), derived from 20:4n-6 and 20:5n-3, were measured in plasma and stimulated blood cells. Levels of TXB2 were greatest in fish fed the BO/TO diet compared to both other treatments, while LTB4 was decreased in fish fed the BO/MO diet compared to both other treatments. In a stress test which involved anaesthesia followed by measurement of recovery times, fish fed the BO/MO diet had significantly lower recovery times compared to fish fed the FO diet.     

Incorporation of n-3 fatty acids into plasma lipid fractions, and erythrocyte membranes and platelets during dietary supplementation with fish, fish oil, and docosahexaenoic acid-rich oil among healthy young men

The effects of n-3 fatty acid supplementation in the form of fresh fish, fish oil, and docosahexaenoic acid (DHA) oil on the fatty acid composition of plasma lipid fractions, and platelets and erythrocyte membranes of young healthy male students were examined. Altogether 59 subjects (aged 19-32 yr, body mass index 16.8-31.3 kg/m2) were randomized into the following diet groups: (i) control group; (ii) fish diet group eating fish meals five times per week [0.38 +/- 0.04 g elcosapentaenoic acid (EPA) and 0.67 +/- 0.09 g DHA per day]; (iii) DHA oil group taking algae-derived DHA oil capsules (1.68 g/d DHA in triglyceride form); and (iv) fish oil group (1.33 g EPA and 0.95 g DHA/d as free fatty acids) for 14 wk. The fatty acid composition of plasma lipids, platelets, and erythrocyte membranes was analyzed by gas chromatography. The subjects kept 4-d food records four times during the study to estimate the intake of nutrients. In the fish diet, in DHA oil, and in fish oil groups, the amounts of n-3 fatty acids increased and those of n-6 fatty acids decreased significantly in plasma lipid fractions and in platelets and erythrocyte membranes. A positive relationship was shown between the total n-3 polyunsaturated fatty acids (PUFA) and EPA and DHA intake and the increase in total n-3 PUFA and EPA and DHA in all lipid fractions analyzed. DHA was preferentially incorporated into phospholipid (PL) and triglyceride (TG) and there was very little uptake in cholesterol ester (CE), while EPA was preferentially incorporated into PL. and CE. The proportion of EPA in plasma lipids and platelets and erythrocyte membranes increased also by DHA supplementation, and the proportion of linoleic acid increased in platelets and erythrocyte membranes in the DHA oil group as well. These results suggest retroconversion of DHA to EPA and that DHA also interferes with linoleic acid metabolism.     

The influence of dietary fatty acid composition on N-ethyl-N-nitrosourea-induced mammary tumour incidence in the rat and on the composition of inositol- and ethanolamine-phospholipids of normal and tumour mammary tissue

This study has investigated the influence of dietary fatty acid composition on mammary tumour incidence in N-ethyl-N-nitrosourea (ENU)-treated rats and has compared the susceptibility to dietary fatty acid modification of the membrane phospholipids phosphatidylinositol (PI) and phosphatidylethanolamine (PE) from normal and tumour tissue of rat mammary gland. The incidence of mammary tumours was significantly lower in fish oil--(29%), compared with olive oil--(75%; P < 0.04) but not maize oil--(63%; P < 0.1) fed animals. No differences in PI fatty acid composition were found in normal or tumour tissue between rats fed on maize oil, olive oil or fish oil in diets from weaning. When normal and tumour tissue PI fatty acids were compared, significantly higher amounts of stearic acid (18:0) were found in tumour than normal tissue in rats given olive oil (P < 0.05). A similar trend was found in animals fed on maize oil, although differences between normal and tumour tissue did not reach a level of statistical significance (P < 0.1). In mammary PE, maize oil-fed control animals had significantly higher levels of linoleic acid (18:2n-6) than either olive oil- or fish oil-fed animals (P < 0.05, both cases) and levels of arachidonic acid were also higher in maize oil- compared with fish oil-fed animals (P < 0.05). In tumour-bearing animals no differences in PE fatty acid composition were found between the three dietary groups. When normal and tumour tissue PE fatty acids were compared, significantly lower amounts of linoleic acid (18:2n-6; P < 0.01) and significantly greater amounts of arachidonic acid (20:4n-6; P < 0.05) were found in tumour than normal tissue of rats fed on maize oil. The present study shows that the fatty acid composition of PI from both normal and tumour tissue of the mammary gland is resistant to dietary fatty acid modification. The PE fraction is more susceptible to dietary modification and in this fraction there is evidence of increased conversion of linoleic acid to arachidonic acid in tumour compared with normal tissue. Lower tumour incidence rates in rats given fish oils may in part be due to alteration in prostanoid metabolism secondary to displacement of arachidonic acid by eicosapentaenoic acid, but PE rather than PI would appear to be the most likely locus for diet-induced alteration in prostanoid synthesis in this tissue. Effects of dietary fatty acids other than on the balance of n-6 and n-3 fatty acids, and on prostanoid metabolism, should also be considered. The significance of increased stearic acid content of PI in tumours of olive oil-fed animals and the possible influence of dietary fatty acids on the capacity for stearic acid accumulation requires further study.     

The influence of gastric juice acidity on the occurrence of esophageal reflux]

Protective properties of n-3 and n-6 polyunsaturated, monosaturated and saturated fatty acids (respectively, n-3 PUFA, n-6 PUFA, MUFA and SFA) against ethanol induced hemorrhagic gastric mucosal lesions were compared. Female Wistar rats (90-100 g) were fed to four weeks semisyntethic diets containing 9% butter (SFA-diet), 6% butter and 3% olive oil (MUFA-diet), 6% butter and 3% sunflower oil (n-6 PUFA-diet) or 6% butter and 3% concentrate of n-3 PUFA ethyl esters (n-3 PUFA-diet). One group of rats received a non-lipid diet. Under all types of lipid containing diets, development of ethanol-induced hemorrhagic gastric mucosal lesions was reduced in compared with non-lipid diet. Cytoprotective effect of n-3 PUFA-E was greater than MUFA and SFA, but smaller than n-6 PUFA.     

Dietary (n-3) and (n-6) polyunsaturated fatty acids rapidly modify fatty acid composition and insulin effects in rat adipocytes

The influence of dietary (n-3) compared with (n-6) polyunsatured fatty acids (PUFA) on the lipid composition and metabolism of adipocytes was evaluated in rats over a period of 1 week. Isocaloric diets comprised 16.3 g/100 g protein, 53.8 g/100 g carbohydrate and 21.4 g/100 g lipids, the latter containing either (n-3) PUFA (32.4 mol/100 mol) or (n-6) PUFA (37.8 mol/100 mol) but having identical contents of saturated, monounsaturated and total unsaturated fatty acids and identical polyunsaturated to saturated fatty acid ratios and double bond indexes. Despite comparable food intake, significantly smaller body weight increments and adipocyte size were observed in rats of the (n-3) diet group after feeding for 1 wk. Rats fed the (n-3) diet also had significantly lower concentrations of serum triglycerides, cholesterol and insulin compared with those fed the (n-6) diet, although levels of serum glucose and free fatty acids did not differ in the two dietary groups. In the (n-6) diet group, the (n-6) and (n-3) PUFA contents of plasma triglycerides, free fatty acids and phospholipids were 30-60% higher and 60-80% lower, respectively, than in the (n-3) diet group, whereas adipocyte plasma membrane phospholipids showed a significantly higher unsaturated to saturated fatty acid ratio and greater fluidity. Glycerol release in response to noradrenaline was significantly higher in the adipocytes of rats fed the (n-3) diet, whereas the antilipolytic effect of insulin generally did not differ in the two groups. Finally, insulin stimulated the transport of glucose and its incorporation into fatty acids to a lesser extent in adipocytes of (n-3) diet fed rats compared with (n-6) diet fed rats. This reduction in the metabolic effects of insulin in rats fed a (n-3) diet for 1 wk could be related to smaller numbers and a lower binding capacity of the insulin receptors on adipocytes and/or to a lesser degree of phosphorylation of the 95 kDa beta subunit of the receptor. In conclusion, dietary intake for 1 wk of (n-3) rather than (n-6) PUFA is sufficient to induce significant differences in the lipid composition and metabolic responses to insulin of rat adipocytes.     

Dietary fish oil (4 g daily) and cardiovascular risk markers in healthy men

Some epidemiological observations indicate that 1 to 2 weekly servings of fish prevent ischemic heart disease (IHD). This might be explained by an effect of the very-long-chain n-3 polyunsaturated fatty acids (n-3 VLCPUFA) of fish oil on lipid metabolism and/or the hemostatic system, both involved in IHD development. We studied the effect of incorporating natural fish oil (4 g daily equivalent to 0.91 g n-3 VLCPUFA and corresponding to one to two weekly servings of fatty fish) into the diet in a 4-week parallel, randomized, and double-blind trial of 47 healthy males aged 29 to 60 years. Sunflower oil was used as placebo. The fish oil had no significant effect on plasma lipids, apolipoproteins, lipoprotein(a), blood coagulation FVII, fibrinogen, endogenous fibrinolysis, beta-thromboglobulin, von Willebrand factor, glucose, or insulin in fasting blood samples. In nonfasting samples (n = 19), fish oil was associated with an approximately 30% decline in plasma triglycerides (P < .02) and a 9% decline in FVII protein (P < .05), whereas FVII coagulant activity and fibrinolysis were unaffected. In conclusion, our findings indicate that lowering of postprandial triglycerides is the only n-3 VLCPUFA effect that could contribute to primary prevention of IHD in healthy middle-aged men as assessed by currently measurable lipid and hemostatic risk markers.     

Molecular characterization of a single mitochondria-associated double-stranded RNA in the green alga Bryopsis

OBJECTIVE: To evaluate the effect of a moderate dose of fish oil on glycemic control and in vivo insulin action in type 2 diabetic men with elevated plasma triacylglycerols and to determine the effect of the same treatment on gene expression of GLUT4, lipoprotein lipase (LPL), and hormone-sensitive lipase (HSL) in the abdominal adipose tissue. RESEARCH DESIGN AND METHODS: A total of 12 type 2 diabetic men were randomly allocated to 2 months of 6 g daily of either fish oil or sunflower oil, separated by a 2-month washout interval, in a double-blind crossover design. RESULTS: For glucose metabolism, 2 months of fish oil supplementation compared with sunflower oil led to similar fasting plasma insulin, glucose, and HbA1c. Basal hepatic glucose production did not increase after fish oil. There was no difference in insulin suppression of hepatic glucose production nor in insulin stimulation of whole-body glucose disposal measured by the euglycemic-hyperinsulinemic clamp. Fish oil did not ameliorate the low mRNA level of GLUT4 in adipose tissue of these patients. For lipid profile, fish oil lowered plasma triacylglycerol more than sunflower oil (P < 0.05) and tended to increase the amount of mRNA of both LPL and HSL in adipose tissue. CONCLUSIONS: A moderate dose of fish oil did not lead to deleterious effects on glycemic control or whole-body insulin sensitivity in type 2 diabetic men, with preserved triacylglycerol-lowering capacities.     

Effect of diet on the rate of depletion of n-3 fatty acids in the retina of the guinea pig

This study has assessed the influence of maternal n-3 long chain polyunsaturated fatty acid supply and dietary manipulation after weaning on the retinal polyunsaturated fatty acid profile. Infant guinea pigs born of dams fed one of two commercial chow diets (differing in the amount of eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids) were raised in two separate experiments, and subsequently partitioned into two diet groups, one supplied with a high level of alpha-linolenic acid (canola oil supplemented), the other with a very low level of alpha-linolenic acid (safflower oil supplemented). Guinea pigs born of dams supplied with the longer chain n-3 fatty acids in the commercial pellets (experiment 2) showed higher levels of retinal docosahexaenoic acid at weaning compared with those born to dams fed chow containing only alpha-linolenic acid (experiment 1). The rate of depletion of retinal docosahexaenoic acid after weaning onto the safflower oil diet was described by a two-stage exponential decay, possibly reflecting systemic and local conservation mechanisms, in conditions of dietary n-3 fatty acid deprivation. The rate of docosahexaenoic acid depletion in the group with the lower retinal docosahexaenoic acid at weaning was more than double the rate of depletion in the group with the higher weaning docosahexaenoic acid value. The endpoint retinal docosahexaenoic acid level at 16 weeks post-weaning after dietary n-3 fatty acid depletion on the safflower oil diet in the group, which started with the lower retinal docosahexaenoic acid level, was approximately half that compared with the group from the dams fed long chain n-3 fatty acids (experiment 1, 5% (interpolated), experiment 2, 9%). These results suggest that an adequately supplied mother is capable of providing an infant with enough n-3 fatty acids to withstand a longer period of dietary deprivation imposed after weaning.     

Alpha-linolenic acid and marine long-chain n-3 fatty acids differ only slightly in their effects on hemostatic factors in healthy subjects

The effects of alpha-linolenic acid (ALA, 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3), and docosahexaenoic acid (DHA, 22:6n-3) on hemostatic factors were compared. Healthy subjects (29 women and 17 men aged 20-44 y) received either linseed oil (average ALA intake: 5.9 g/d) or fish oil plus sunflower oil (average EPA + DHA intake: 5.2 g/d) for 4 wk. The supplemented amount of fat was 1.19 mg/kJ (1 g/200 kcal) calculated energy expenditure. Stability of habitual diets was monitored. Blood samples were collected at baseline, at the end of the experimental period, and after a 12-wk follow-up period. Different changes in the study groups were seen only in serum cholesterol and triacylglycerols, platelet fatty acid composition, and ADP-induced platelet aggregation. The treatments did not differ in their effects on collagen-induced platelet aggregation and thromboxane production, aggregation to the thromboxane A2 mimic I-BOP, urinary excretion of 11-dehydro-thromboxane B2 and beta-thromboglobulin, bleeding time, plasma fibrinogen concentration, antithrombin III activity, factor VII coagulant activity, or activity of plasminogen activator inhibitor 1. The results indicate that supplemented ALA from vegetable oil and EPA and DHA from a marine source have largely parallel effects on hemostatic factors.     

Dietary fat type and energy restriction interactively influence plasma leptin concentration in rats

To investigate whether dietary fat source and energy restriction interactively influence plasma leptin levels and its association of leptin with insulin action, rats were fed diets containing either fish, safflower oil, or beef tallow (20% wt/wt) for 10 weeks. Groups of rats consumed each diet ad libitum or at 85% or 70% of ad libitum energy intake in a design that held fat intake constant. Graded levels of energy restriction caused body weight to decrease (P < 0.001) differently according to the dietary fat provided. Plasma leptin concentrations were 60% higher (P < 0.05) in the groups fed fish oil and safflower oil ad libitum compared with those in the beef tallow group, despite smaller perirenal fat mass and fat cell size in the fish oil-fed animals. Energy restriction resulted in a 62% decrease (P < 0.05) in leptin levels in fish oil- and safflower oil-fed rats, whereas no changes were observed in beef tallow-fed animals. Plasma insulin levels were lower (P < 0.05) in the fish oil group fed ad libitum compared with those in the two other diet groups. These data demonstrate a hyperleptinemic effect in animals consuming diets rich in polyunsaturated fatty acid, which can be normalized to the level of saturated fat consumption by mild energy restriction. Thus, dietary fatty acid composition, independent of adipose tissue mass, is an important determinant of circulating leptin level in diet-induced obesity.     

Quality of care in outpatient clinic for female diseases. A study of the perception of patients with infertility problems

Influence of dietary w-6 and w-3 polyunsaturated fatty acids (PUFA), monounsaturated fatty acids (MUFA) and saturated fatty acids (SFA) on development of rat paw edema induced by dextran subplantar injection was studied. Female Wistar rats the initial weight 150-160 g were bed fo four weeks diets containing as lioid components 6% butter and 3% sunflower oil (w-6 PUFA-diet), 6% butter and 3% fish oil (w-3 PUFA-diet), 6% butter and 3% olive oil (MUFA-diet) or butter (SFA-diet). One group of rats received a non-lipid diet. The development of rat paw edema was reduced under the w-3 PUFA-diet in comparison with the w-6 PUFA-diet, but more intensive then under the non-lipid diet. No differences were detected in effects on inflammation induced w-3 PUFA-, MUFA-, and SFA-diets.     

Alteration in 5'-nucleotidase activities and composition of liver and brain microsomes of developing rats fed different dietary fats

Four groups of male weanling rats were fed during three months, diets different in the nature of fats and the activity of 5' nucleotidase and fatty acid composition of brain and liver microsomes were studied. Group A were fed a standard commercial diet, group B a fat free-diet and group C and D a fat free-diet, containing respectively 10% of peanut-rapeseed oil and 10% of salmon oil. In brain and liver microsomes, 5'-nucleotidase activity increased throughout the development for all diets (except for the fat-free diet). Slight differences were found in rats fed the peanut-rapeseed oil diet compared to controls estimated at the same time. However, in animals fed the fish-oil diet, 5' nucleotidase had the highest activity in both brain and liver microsomes. Marked changes occurred in the fatty acid patterns of brain and liver microsomes among the various groups. The greatest alterations were found in the liver microsomes. In brain and liver microsomal membranes the fat-free diet induced an increase in monounsaturated fatty acids, an synthesis of eicosatrienoic acid, and a decrease in (n-6) and (n-3) polyunsaturated fatty acids. Animals fed a peanut-rapeseed oil and control diet showed similar fatty acid patterns in liver and brain microsomes. However, when rats were fed a fish-oil diet, the liver microsomal membranes were highly enriched in eicosapentaenoic and docosahexaenoic acids, and simultaneously there was a decrease in arachidonic acid. These results suggest that manipulation of the lipid environment influences 5'-nucleotidase activity by the interaction of the enzyme with specific membrane lipids.     

Monosodium glutamate (MSG)-obese rats develop glucose intolerance and insulin resistance to peripheral glucose uptake

Different levels of insulin sensitivity have been described in several animal models of obesity as well as in humans. Monosodium glutamate (MSG)-obese mice were considered not to be insulin resistant from data obtained in oral glucose tolerance tests. To reevaluate insulin resistance by the intravenous glucose tolerance test (IVGTT) and by the clamp technique, newborn male Wistar rats (N = 20) were injected 5 times, every other day, with 4 g/kg MSG (N = 10) or saline (control; N = 10) during the first 10 days of age. At 3 months, the IVGTT was performed by injecting glucose (0.75 g/kg) through the jugular vein into freely moving rats. During euglycemic clamping plasma insulin levels were increased by infusing 3 mU.kg-1.min-1 of regular insulin until a steady-state plateau was achieved. The basal blood glucose concentration did not differ between the two experimental groups. After the glucose load, increased values of glycemia (P < 0.001) in MSG-obese rats occurred at minute 4 and from minute 16 to minute 32. These results indicate impaired glucose tolerance. Basal plasma insulin levels were 39.9 +/- 4 microU/ml in control and 66.4 +/- 5.3 microU/ml in MSG-obese rats. The mean post-glucose area increase of insulin was 111% higher in MSG-obese than in control rats. When insulinemia was clamped at 102 or 133 microU/ml in control and MSG rats, respectively, the corresponding glucose infusion rate necessary to maintain euglycemia was 17.3 +/- 0.8 mg.kg-1.min-1 for control rats while 2.1 +/- 0.3 mg.kg-1.min-1 was sufficient for MSG-obese rats. The 2-h integrated area for total glucose metabolized, in mg.min.dl-1, was 13.7 +/- 2.3 vs 3.3 +/- 0.5 for control and MSG rats, respectively. These data demonstrate that MSG-obese rats develop insulin resistance to peripheral glucose uptake.     

Immunoregulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids

1. Fish oils are rich in the long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids. Linseed oil and green plant tissues are rich in the precursor fatty acid, alpha-linolenic acid (18:3n-3). Most vegetable oils are rich in the n-6 PUFA linoleic acid (18:2n-6), the precursor of arachidonic acid (20:4n-6). 2. Arachidonic acid-derived eicosanoids such as prostaglandin E2 are pro-inflammatory and regulate the functions of cells of the immune system. Consumption of fish oils leads to replacement of arachidonic acid in cell membranes by eicosapentaenoic acid. This changes the amount and alters the balance of eicosanoids produced. 3. Consumption of fish oils diminishes lymphocyte proliferation, T-cell-mediated cytotoxicity, natural killer cell activity, macrophage-mediated cytotoxicity, monocyte and neutrophil chemotaxis, major histocompatibility class II expression and antigen presentation, production of pro-inflammatory cytokines (interleukins 1 and 6, tumour necrosis factor) and adhesion molecule expression. 4. Feeding laboratory animals fish oil reduces acute and chronic inflammatory responses, improves survival to endotoxin and in models of autoimmunity and prolongs the survival of grafted organs. 5. Feeding fish oil reduces cell-mediated immune responses. 6. Fish oil supplementation may be clinically useful in acute and chronic inflammatory conditions and following transplantation. 7. n-3 PUFAs may exert their effects by modulating signal transduction and/or gene expression within inflammatory and immune cells.     

A study of laboratory based faecal occult blood testing in Melbourne, Australia. The Faecal Occult Blood Testing Study Group

The effects of chromium (Cr) supplementation on diet-induced insulin resistance produced by feeding a high-fat, low-Cr diet were studied in rats to ascertain the role of Cr in insulin resistance. Wistar male rats were maintained for 16 weeks after weaning on a basal diet containing 40% lard, 30% sucrose, and 25% casein by weight and adequate vitamins and minerals without added Cr (-Cr). Fasting levels of insulin, glucose, and triglycerides and the responses during an intravenous glucose tolerance test (IVGTT) were compared as indices of insulin resistance and the effectiveness of dietary Cr. IVGTTs and blood sampling for data analyses were performed over a 40-minute period after IV glucose injection (1.25 g/kg body weight) in overnight-fasted animals under pentobarbital anesthesia (40 mg/kg body weight). All animals were normoglycemic (-Cr, 109 +/- 3 mg/dL; +Cr, 119 +/- 5), with fasting insulin levels elevated in the -Cr group (65 +/- 10 microU/mL) versus the +Cr group (31 +/- 4 microU/mL). Increases in plasma triglycerides in the -Cr group were not significant. Following glucose injection, the rate of glucose clearance was lower in the -Cr group (1.74 +/- 0.22 v2.39 +/- 0.11%/min), and 40-minute glucose areas in the -Cr group tended to be higher than in the +Cr group. The insulin response to glucose injection was 20% higher in the -Cr group. Forty-minute plasma triglyceride areas were lower in +Cr rats (875 +/- 62 v 1,143 +/- 97 mg/dL.min in -Cr rats). These data demonstrate that the insulin resistance induced by feeding a high-fat, nutrient-stressed diet is improved by Cr.     

Fatty acid composition in maternal milk and plasma during supplementation with cod liver oil

OBJECTIVE: We investigated how cod liver oil influences the amount of essential fatty acids in mothers' breast milk. DESIGN AND INTERVENTION: Lactating mothers (n =22) were randomized into four groups 3-8 weeks after parturition. They were supplemented for 14 days with 0, 2.5, 5 and 10 ml cod liver oil (7.7 g eicosapentaenoic acid (EPA, 20:5n-3), 10.2 g docosahexaenoic acid (DHA, 22:6n-3) and 22.9 g n-3 fatty acids in total per 100 ml). RESULTS: In maternal plasma phospholipids there was an increase in the content of EPA and DHA in the group supplemented with 10 ml cod liver oil daily (P < or = 0.05). DHA concentrations in breast milk pre-supplementation ranged from 0.15 to 1.56 wt% and increased in all supplemented groups (P< or =0.05). The concentration of EPA in breast milk increased in the groups supplemented with 5 or 10 ml cod liver oil (P< or =0.05), whereas the concentration of arachidonic acid (AA, 20:4n-6) did not change in any of the supplemented groups. Total intake of DHA adjusted to body mass index (BMI), correlated to DHA concentrations in plasma (r = 0.49, P = 0.02) and breast milk (r = 0.45, P = 0.04). The concentration of tocopherol did not change during the supplementation period, neither in plasma nor in breast milk. CONCLUSION: Dietary intake of DHA is reflected in the concentration of DHA in breast milk, without affecting the concentration of AA or tocopherol.