Dietary fiber--nostrum or critical nutrient?
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Animals↗
Biomedical subjects
W E Connor
Publications and source records attributed to W E Connor.
The differential effect of eicosapentaenoic acid and oleic acid on lipid synthesis and VLDL secretion in rabbit hepatocytes.
The suppression of plasma very low density lipoprotein (VLDL) triglyceride levels by dietary fish oils rich in polyunsaturated n-3 fatty acids has been attributed to decreased hepatic VLDL secretion. To investigate the effect of n-3 fatty acids on lipid metabolism and VLDL secretion in a tissue culture system, we incubated rabbit hepatocytes with oleic acid and eicosapentaenoic acid (EPA) and examined [3H]glycerol and [14C]fatty acid incorporation into hepatocyte triglyceride and phospholipid and into media VLDL. Glycerol incorporation studies showed that EPA failed to stimulate VLDL triglyceride secretion from hepatocytes as occurred with oleic acid (P less than 0.05). Oleic acid preferentially enhanced hepatocyte triglyceride synthesis while EPA stimulated significantly phospholipid synthesis (P less than 0.01). Varying the relative concentrations of oleic acid and EPA at a constant total fatty acid concentration corroborated preferential triglyceride synthesis from oleic acid. Synthesis shifted predominantly to phospholipids with increasing concentrations of EPA and lower levels of oleic acid. Incorporation of the [14C]fatty acids (800 microM) followed similar patterns: 87% of [14C]oleic acid was incorporated into hepatocyte triglyceride and 44% of [14C]EPA was assimilated in hepatocyte phospholipid (p less than 0.001). Fatty acids at trace concentrations (53 nM) showed a more divergent pattern of lipid incorporation: 60% of [14C]oleic acid was incorporated into triglyceride while 91% of [14C]EPA was incorporated into phospholipid (p less than 0.001). We conclude that in primary rabbit hepatocyte culture, which appears to be a useful model to study lipid metabolism and VLDL secretion, EPA is avidly incorporated into phospholipid while oleic acid predominantly becomes esterified in triglyceride.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Polydipsia in rhesus monkeys deficient in omega-3 fatty acids.
Omega-3 fatty acids are a major component of neural membranes. They are essential nutrients for normal biochemical development of the brain and retina and may affect behavior. In our studies of long-term dietary omega-3 fatty acid deficiency, we have found a new effect of this deficiency in rhesus monkeys. Deficient monkeys visited the home cage drinking spout more frequently than controls (Experiment 1), and drank more water over 24 hours (Experiment 2). The increase in intake was mirrored by increased combined output of urine + feces over 24 hours (Experiment 3), and was not due to spillage (Experiment 4). The dietary deficiency greatly reduced omega-3 fatty acids in red blood cells but did not affect serum electrolyte levels. The changes in fluid intake and output may be related to direct or indirect effects on central or peripheral control mechanisms for drinking or excretion, which may be mediated by altered composition of neural or other membranes or changes in eicosanoid metabolism.
Animals↗
Placental transfer of essential fatty acids in humans: venous-arterial difference for docosahexaenoic acid in fetal umbilical erythrocytes.
Docosahexaenoic acid [22:6(n-3); 22:6(4,-7,10,13,16,19) (DHA)] is required in quantity by the developing nervous system of the fetus. This need could be met through synthesis of DHA from linolenic acid in the fetus or through placental transfer of DHA directly. To study the placental transfer of n-3 fatty acids, we obtained umbilical and maternal blood samples from 26 healthy women and infants at parturition and measured the fatty acid composition and content of both plasma and erythrocytes. A striking finding was a considerable venous-arterial difference for DHA in the umbilical erythrocytes as a proportion of total fatty acids and in absolute concentration. This difference of 2.2 micrograms per billion erythrocytes was 6 times larger than the difference in fetal plasma, when the plasma and erythrocyte concentrations were normalized to whole blood. Most other erythrocyte fatty acids showed a similar trend. In umbilical plasma, significant venous-arterial differences were found for 16:0, 16:1, 18:2, and total saturated fatty acids. There was a similar trend for most other plasma fatty acids. Compared with maternal blood, fetal plasma and erythrocytes had higher levels of 20:4 and DHA and lower levels of 18:2 and 18:3(n - 3) fatty acids as a proportion of total fatty acids. These results suggest that erythrocytes play a major role in the necessary transport of the essential fatty acid DHA into the fetus.
Arachidonic Acid↗
Fish oils in hypertriglyceridemia: a dose-response study.
The effects of three supplemental doses of fish oil on plasma lipids, lipoproteins, and bleeding times were studied in ten hypertriglyceridemic patients. After a 3-wk baseline period each patient was given 15, 25, or 40 mL fish oil/d (containing 4.5, 7.5, and 12 g n-3 fatty acids) for three successive 6-wk periods, each separated by a 4-wk period of no supplementation. Plasma cholesterol concentrations decreased from 7.40 mmol/L to 6.35, 6.55, and 6.40 mmol/L with increasing doses of fish oil (p less than 0.01 vs baseline for each). Plasma triglyceride concentrations decreased from 6.10 mmol/L to 2.90, 2.80, and 2.35 mmol/L (p less than 0.01 vs baseline for each). Low-density-lipoprotein cholesterol concentrations increased significantly (by 23% and 28%) with the two higher doses, respectively. Bleeding times increased only with the largest dose. The lowest dose was the most hypolipidemic per gram n-3 fatty acids.
Adult↗
Effects of dietary n-3 fatty acids on the phospholipid molecular species of monkey brain.
We examined the changes in the molecular species of brain ethanolamine glycerophospholipids of monkeys fed diets containing widely ranging amounts of n-3 fatty acids. Two groups of rhesus monkeys were fed pre- and postnatally either a control diet (soy oil; containing 8% of fatty acids as 18:3n-3) or a deficient diet (safflower oil; containing less than 0.3% 18:3n-3). The brains of these animals were analyzed at 22 months of age. A third group of monkeys was fed the safflower oil diet to 22 months of age and then switched to a fish oil diet (28% long-chain n-3 fatty acids) for 1-2 years before autopsy. The molecular species of the diacyl, alkylacyl, and alkenylacyl ethanolamine glycerophospholipids from frontal cortex were separated by HPLC. A total of 24 molecular species were identified. Fatty acids in the sn-2 position differed markedly among the diet groups, but the sn-1 position always contained only 16:0, 18:0, or 18:1. In the diacyl subclass of the control brain, the n-3 molecular species represented 41% of total and the n-6 species 45%, whereas in the deficient brain the n-3 molecular species decreased to 9% and n-6 molecular species increased to 77%. The fatty acid 22:5n-6 did not replace 22:6n-3 in a symmetrical fashion in the molecular species of the deficient brain. In the brains of the fish oil-fed monkeys, the n-3 molecular species amounted to 61% and n-6 molecular species were reduced to 25%. The species 18:1-22:6, 16:0-22:6, and 18:0-22:6 generally changed proportionally in response to diet.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Increased activity of factor VII and factor VII-phospholipid complex measured using a Normotest system in subjects with hyperlipidemia.
Coagulation factor VII and factor VII-phospholipid complex (factor VIIpl), an activated form of factor VII, were measured using a Normotest system in 128 patients with various types of hyperlipoproteinemias and in 45 control subjects. A positive correlation was found between both factors VII (p less than 0.001) and VIIpl (p less than 0.0001) and serum triglycerides. Similar correlations were established with very low density lipoproteins. A positive correlation was also observed between factor VIIpl and total cholesterol, whereas inverse correlations were found with high-density lipoproteins for both factors VII and VIIpl. No positive correlation could be found between low-density lipoproteins and factors VII and VIIpl. This study has shown that patients with hyperlipoproteinemias associated with high serum triglyceride levels, with or without high cholesterol levels, have increased activity of factors VII and VIIpl, both previously associated with an increased risk of coronary heart disease.
Adult↗
Docosahexaenoic acid is the preferred dietary n-3 fatty acid for the development of the brain and retina.
The metabolism of individual dietary n-3 fatty acids was studied in n-3 fatty acid-deficient newly hatched chicks. Laying hens were fed the n-6 fatty acid, ethyl linoleate, as the only source of polyunsaturated fat. Chicks were then fed the n-3-deficient hens' diet, or one of three other diets supplemented with the ethyl ester of 18:3 n-3, 20:5 n-3 [eicosapentaenoic acid (EPA)], or 22:6 n-3 [docosahexaenoic acid (DHA)] at 0.44% of calories. At the end of 0, 1, 2, and 3 wk, the fatty acid composition of the brain, retina, liver, and serum was determined. Dietary EPA and DHA were equally effective at raising levels of DHA in the brain and retina. Dietary 18:3 was relatively ineffective in restoring brain and retina DHA. In the n-3-deficient chicks fed EPA or DHA, levels of DHA recovered to control values in both the brain and retina by 3 wk. Very little EPA accumulated in the brain or retina of chicks fed EPA. Hepatic synthesis of DHA from EPA appeared low, suggesting that the brain and retina synthesized the DHA that accumulated rapidly in these tissues after the feeding of EPA. The delta-4-desaturase enzyme was apparently very active, then, in the brain and retina. Retroconversion of dietary 22:6 to 22:5 and 20:5 was evident in the serum, liver, and retina but not in the brain. Thus, it was possible to study the relative metabolism and especially the interconversion of n-3 fatty acids in a environment uncomplicated by existing stores of these essential fatty acids. This study would suggest that 18:3 as the sole source of n-3 fatty acids in the diets of animals, including the human infant, may not be adequate for the biochemical development of the brain and retina and that dietary DHA is the preferred fatty acid of the n-3 series.
Animals↗
Dietary effects on brain fatty acid composition: the reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys.
Rhesus monkeys given pre- and postnatal diets deficient in n-3 essential fatty acids develop low levels of docosahexaenoic acid (22:6 n-3, DHA) in the cerebral cortex and retina and impaired visual function. This highly polyunsaturated fatty acid is an important component of retinal photoreceptors and brain synaptic membranes. To study the turnover of polyunsaturated fatty acids in the brain and the reversibility of n-3 fatty acid deficiency, we fed five deficient juvenile rhesus monkeys a fish oil diet rich in DHA and other n-3 fatty acids for up to 129 weeks. The results of serial biopsy samples of the cerebral cortex indicated that the changes of brain fatty acid composition began as early as 1 week after fish oil feeding and stabilized at 12 weeks. The DHA content of the phosphatidylethanolamine of the frontal cortex increased progressively from 3.9 +/- 1.2 to 28.4 +/- 1.7 percent of total fatty acids. The n-6 fatty acid, 22:5, abnormally high in the cerebral cortex of n-3 deficient monkeys, decreased reciprocally from 16.2 +/- 3.1 to 1.6 +/- 0.4%. The half-life (t 1/2) of DHA in brain phosphatidylethanolamine was estimated to be 21 days. The fatty acids of other phospholipids in the brain (phosphatidylcholine, -serine, and -inositol) showed similar changes. The DHA content of plasma and erythrocyte phospholipids also increased greatly, with estimated half-lives of 29 and 21 days, respectively. We conclude that monkey cerebral cortex with an abnormal fatty acid composition produced by dietary n-3 fatty acid deficiency has a remarkable capacity to change its fatty acid content after dietary fish oil, both to increase 22:6 n-3 and to decrease 22:5 n-6 fatty acids. The biochemical evidence of n-3 fatty acid deficiency was completely corrected. These data imply a greater lability of the fatty acids of the phospholipids of the cerebral cortex than has been hitherto appreciated.
Animals↗
Effects of fish oil on VLDL triglyceride kinetics in humans.
Dietary n-3 fatty acids (FAs) found in fish oils markedly lower plasma triglyceride (TG) and very low density lipoprotein (VLDL) levels in both normal and hypertriglyceridemic subjects. The present study examined the mechanism of this effect. Ten subjects with widely different plasma triglyceride levels (82 to 1002 mg/dl) were fed metabolically controlled diets containing 20% fat. The control diet contained a blend of cocoa butter and peanut oil (P/S = 0.8). The test diet contained fish oil (P/S = 1.1) and provided 10-17 g of n-3 FAs per day (depending on calorie intake). After 3 to 5 weeks of each diet, the kinetics of VLDL-TG were determined over a 48-h period after the injection of [3H]glycerol. The fish oil diet reduced the VLDL-TG synthetic rate from 23 +/- 14.3 (mean +/- SD) to 12.6 +/- 7.5 mg/h per kg ideal weight (P less than 0.005) and increased the fractional catabolic rate (FCR) for VLDL-TG from 0.23 +/- 0.12 to 0.38 +/- 0.16 h -1 (P less than 0.005). At the same time, there was a 66% reduction of plasma triglyceride levels, resulting largely from a 78% decrease in VLDL-TG levels (398 +/- 317 to 87 +/- 77 mg/dl; P less than 0.005). There was a strong correlation (r = 0.83; P less than 0.01) between the change in synthetic rates and pool sizes, but there was no correlation (r = 0.24; NS) between changes in FCRs and pool sizes. The VLDL cholesterol: triglyceride ratio increased during the n-3 diet suggesting that smaller VLDL particles were present. These particles would be expected to leave the VLDL fraction more rapidly than larger particles producing a higher FCR. We conclude that the hypotriglyceridemic effect of fish oil appears to be caused primarily by an inhibition of very low density lipoprotein-triglyceride synthesis, but an additional, independent effect upon VLDL catabolism cannot be ruled out.
Dietary Fats, Unsaturated↗
Diet, atherosclerosis, and fish oil.
The principal goal of dietary prevention and treatment of atherosclerotic coronary heart disease is the achievement of physiological levels of the plasma total and LDL cholesterol, triglyceride, and VLDL. These goals have been well delineated by the National Cholesterol Education Program of the National Heart, Lung and Blood Institute and the American Heart Association. Dietary treatment is first accomplished by enhancing LDL receptor activity and at the same time depressing liver synthesis of cholesterol and triglyceride. Both dietary cholesterol and saturated fat decrease LDL receptor activity and inhibit the removal of LDL from the plasma by the liver. Saturated fat decreases LDL receptor activity, especially when cholesterol is concurrently present in the diet. The total amount of dietary fat is of importance also. The greater the flux of chylomicron remnants is into the liver, the greater is the influx of cholesterol ester. In addition, factors that affect VLDL and LDL synthesis could be important. These include excessive calories (obesity), which enhance triglyceride and VLDL and hence LDL synthesis. Weight loss and omega-3 fatty acids from fish oil depress synthesis of both VLDL and triglyceride in the liver. The optimal diet for the treatment of children and adults to prevent coronary disease has the following characteristics: cholesterol (100 mg/day), total fat (20% of calories, 6% saturated with the balance from omega-3 and omega-6 polyunsaturated and monounsaturated fat), carbohydrate (65% of calories, two thirds from starch including 11 to 15 gm of soluble fiber), and protein (15% of calories). This low-fat, high-carbohydrate diet can lower the plasma cholesterol 18% to 21%. This diet is also an antithrombotic diet, thrombosis being another major consideration in preventing coronary heart disease. Dietary therapy is the mainstay of the prevention and treatment of coronary heart disease through the control of plasma lipid and lipoprotein levels. The exact place of the omega-3 fatty acids from fish and fish oil remains to be defined. However, this much seems certain. Fish provides an excellent substitute for meat in the diet. Fish is lower in fat, especially saturated fat, and contains the omega-3 fatty acids. Fish oil may have promise as a therapeutic agent in certain hyperlipidemic states, especially the chylomicronemia of type V hyperlipidemia. Fish oil has logical and well-defined antithrombotic and anti-atherosclerotic activities since it depresses thromboxane A2 production and inhibits cellular proliferation responsible for the progression of atherosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
The hypolipidemic effects of gemfibrozil in type V hyperlipidemia. A double-blind, crossover study.
Thirteen patients with phenotypic type V hyperlipidemia were treated with either gemfibrozil (Lopid) or a placebo in a randomized, double-blind, crossover study for two 8-week periods. A 4-week baseline period of a low-fat diet preceded the study and served as a dietary control period. A 4-week washout period followed the two 8-week periods. Compared with the placebo phase, gemfibrozil produced a significant reduction in the concentrations of total plasma triglycerides (21.03 vs 5.50 mmol/L) and very low-density lipoprotein triglycerides (14.40 vs 4.59 mmol/L) as well as in total plasma cholesterol levels (10.88 vs 5.62 mmol/L) and very low-density lipoprotein cholesterol (6.66 vs 2.15 mmol/L). Chylomicronemia was virtually abolished by the drug treatment. As expected in treated patients with type V hyperlipidemia, concentrations of low-density lipoprotein cholesterol rose after therapy with gemfibrozil (3.08 mmol/L) as compared with placebo (1.84 mmol/L); high-density lipoprotein cholesterol also increased (0.85 mmol/L after therapy with gemfibrozil, 0.62 mmol/L after placebo). The previously very low values for both of these lipoproteins increased at the same time that the total plasma cholesterol value decreased. We conclude that gemfibrozil is a well-tolerated and effective hypolipidemic agent for the treatment of patients with severe hypertriglyceridemia when used in conjunction with a low-fat diet.
Adult↗
On the demonstration of omega-3 essential-fatty-acid deficiency in humans.
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Animals↗
Hypolipidaemic effects of n-3 fatty acids in primary hyperlipoproteinaemia.
The influence of fish oils rich in n-3 fatty acids on plasma lipid and lipoprotein concentrations in patients with primary hyperlipoproteinaemia is reviewed. When used as a dietary supplement, n-3 fatty acids exert their greatest effect on the concentrations of triglyceride-rich lipoproteins and these effects are dose dependent. Low doses of n-3 fatty acids reduce plasma triglyceride concentrations in patients with phenotypic type IV, type V and type IIB hyperlipoproteinaemia, but concurrently result in modest increases in the plasma concentrations of low density lipoprotein (LDL). With very high doses plasma concentrations of LDL cholesterol decrease in patients with the type IIB phenotype. At low doses n-3 fatty acids do not significantly lower concentrations of LDL cholesterol in patients with primary hypercholesterolaemia whereas at higher doses a modest LDL lowering effect is achieved. The results indicate that the therapeutic potential of n-3 fatty acids as hypolipidaemic agents is greatest in patients with hypertriglyceridaemia.
Cholesterol↗
Arguments about the atherogenic potential of foods.
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Arteriosclerosis↗
Rapid modulation of the n-3 docosahexaenoic acid levels in the brain and retina of the newly hatched chick.
The newly hatched chick obtains its fatty acids almost completely from the lipids of the egg yolk as these are transferred to the developing embryo during its 21-day period of incubation. Since the diet of the laying hen greatly influences the fatty acid composition of the egg lipids, and presumably also the fatty acid composition of the resulting chick, we tested how quickly and to what extent varying the amount of n-3 fatty acids in the diet of the hen would modulate the level of n-3 fatty acids in the brain and retina of the newly hatched chick. White Leghorn hens were fed commercial or semi-purified diets supplemented with 10% fish oil, linseed oil, soy oil, or safflower oil. Eggs, together with the brain, retina, and serum of newly hatched chicks, were then analyzed for fatty acid composition. The fatty acids of egg yolk responded quickly to the hen's diet with most of the change occurring by 4 weeks. There was a linear relationship between the linolenic acid content of the diets and levels of this fatty acid in egg yolk and chick serum. In chicks from hens fed the fish oil diet, the total n-3 fatty acids, including 22:6(n-3), were elevated twofold in the brain and retina and sevenfold in serum relative to commercial diet controls. The safflower oil diet led to a very low n-3 fatty acid content in egg yolks and only 25% of the control n-3 fatty acid content in the brain and retina of chicks.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The cholesterol-saturated fat index for coronary prevention: background, use, and a comprehensive table of foods.
The potential of a food or a diet to raise the plasma level of total and low-density-lipoprotein cholesterol and to promote atherosclerosis is directly related to its cholesterol and saturated fat content. A new formula that indicates the concentrations of cholesterol and saturated fat in foods, termed the cholesterol-saturated fat index (CSI), has been devised. A low CSI indicates low saturated fat and/or cholesterol content and thus hypocholesterolemic and low atherogenic potential. Guidelines are provided for using the CSI to evaluate or plan low-fat diets, for comparing a food or a mixed dish with others, and for evaluating a day's food intake. A comprehensive table of foods is presented.
Cholesterol, Dietary↗
Aneurysmal coronary artery disease in cerebrotendinous xanthomatosis.
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Adult↗