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The effects of (n-3) fatty acids on the postprandial state were investigated by monitoring the alimentary responses to identical test meals fed to adults [n = 11; fasting triacylglycerol (TG) 2.55 +/- 0.24 mmol/L; mean +/- SEM] after a self-selected diet baseline period (BLP) and then after a 6-wk (n-3) fatty acid period (FOP) [ approximately 5.2 g (n-3) fatty acids] and a 6-wk control oil period (COP) administered in random order. Samples were drawn immediately prior to the test meal (time 0) and then hourly from 2 to 6 h postmeal. Postprandial plasma triacylglycerol (TG) and TG-rich lipoprotein (TRL) TG apo B48, and B100 absolute concentrations were significantly lower after FOP than after COP or BLP, while plasma cholesterol was unchanged. Normalizing the results as increments over time 0 eliminated the diet effect on all but plasma TG. Time remained a significant effect for plasma TG, TRL TG, and TRL TC. Finally, only absolute TRL B48 and absolute and incremental plasma TG concentrations displayed significant time-diet interactions. These results suggest that postprandial TRL apo B reductions are likely caused by (n-3) fatty acid suppression of both hepatic and intestinal apoB secretion/synthesis. Altered TRL metabolism, i.e. changes in postprandial TG, cholesterol, apo B48, and increase in LDL particle size, may represent an additional mechanism for the reduced heart disease risk associated with fish [(n-3) fatty acid] consumption. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether the addition of soy protein and guar gum to the American Heart Association (AHA) Step I diet would increase its efficacy compared with the typical "Average American Diet" (AAD) in a non-human primate model. Twenty adult female cynomolgus monkeys (Macaca fascicularis) were fed one of three diets for 6 wk. The AAD contained 36% energy from fat; the standard Step I diet contained 30% energy from fat; and the modified AHA Step I diet contained 30% energy from fat with the addition of soy protein isolate (10% of total energy) and guar gum (5.8 g/d). Plasma samples were collected from food-deprived monkeys at 4, 5 and 6 wk of dietary treatment for analyses of plasma total cholesterol (TC), lipoprotein cholesterol and triacylglycerol (TAG) concentrations. Plasma TC, LDL-C, HDL-C and TAG concentrations were not significantly different in wk 4, 5 and 6 within any of the diet periods; thus the three measurements were averaged. After 6 wk of dietary treatment, monkeys fed the standard Step I diet had lower plasma TC (-19%) (P < 0.05) and LDL cholesterol (LDL-C) (-24%) (P < 0.09) than when they were fed the AAD, with no effect on HDL cholesterol (HDL-C), the lipoprotein cholesterol profile or TAG. Beyond the effect of the standard Step I diet, the modified AHA Step I diet further reduced plasma TC and LDL-C (-24% and -40%) (P < 0. 05) and the TC/HDL-C and LDL-C/HDL-C ratios (-37% and -52%) (P < 0. 05) with no significant changes in plasma HDL-C or TAG. The primary conclusions of this study are that the efficacy of the AHA Step I cholesterol-lowering diet can be increased with the addition of soy protein and guar gum and provide a more favorable lipoprotein cholesterol profile. Whether the cholesterol-lowering effect is the result of soy protein or guar gum or a synergistic effect of both remains to be determined. [ABSTRACT FROM AUTHOR]

Chronic diseases develop in susceptible individuals following exposure to environmental conditions including high fat diets. Inbred strains of mice differing in susceptibility to atherosclerosis, diabetes, obesity and certain cancers are models for understanding the genetic basis and molecular mechanisms whereby diet influences these polygenic and multifactorial disorders. Expression sequence tags (EST) and disease quantitative trait loci (QTL) are also being identified with these strains. Reported here are comparisons of food intake, growth, nonfasting serum lipids and expression of mRNA for hepatic apolipoprotein E (ApoE), hepatic stearoyl CoA desaturase (Scd1) and heart lipoprotein lipase (Lpl) in a 2 x 2 x 2 design with C57BL/6J and BALB/cByJ mice fed semipurified diets with 4 or 20% saturated (coconut) or unsaturated (corn) oils for 4 mo. Histological studies of aortas and coronary arteries are also reported for these animals. After 4 mo, BALB/cByJ mice were significantly heavier and had significantly higher total serum cholesterol, HDL cholesterol and triglyceride concentrations in the fed state than C57BL/6J mice. Efficiency of utilizing dietary energy did not differ consistently between strains. Oil level affected serum total cholesterol, triglycerides and HDL cholesterol, which were significantly greater in mice fed high fat diets. Lpl and ApoE mRNA expression levels were not significantly affected by mouse strain, oil source or oil level. Scd1 mRNA expression, however, was significantly higher in C57BL/6J than in BALB/cByJ mice and was lower in all mice fed 20% compared with those fed 4% fat diets. Genes regulated differently by diet among strains with distinct susceptibility to diet-influenced disease may be associated with molecular pathways contributing to incidence or severity. [ABSTRACT FROM AUTHOR]

Background: Liquid-formula diets (LFDs) are useful in metabolic studies of the cholesterolemic effects of dietary lipids because they can be formulated with accuracy, facilitating precise delivery of fatty acids of interest. However, because of differences in composition and nutrient delivery between LFDs and solid-food diets (SFDs), there is a need to determine differences in their effects., Objective: Our objective was to compare lipid and lipoprotein responses to changes in total fat, saturated fatty acids (SFAs), and cholesterol in subjects consuming an SFD or LFD., Design: Twenty-one healthy subjects consumed controlled diets representative of an average American diet [AAD; 37% of energy from fat (15% from SFAs), and <50 mg cholesterol/MJ] or a National Cholesterol Education Program (NCEP) Step II diet [26% fat (5% from SFAs) and <25 mg cholesterol/MJ]. Other nutrients were similar between diets. Diets were consumed for 23 d in a randomized, crossover design., Results: For the AAD and NCEP Step II diet, there were no significant differences in lipids and apolipoproteins when the LFD or SFD versions were consumed. In contrast, consumption of the SFD was associated with significantly lower total cholesterol and triacylglycerols than was consumption of the corresponding AAD or Step II LFD (P < 0.05). Subjective ratings of satiety, hunger, and quality of life between diet forms did not differ significantly., Conclusions: Both LFDs and SFDs yield quantitatively similar cholesterolemic responses to changes in dietary fat, SFAs, and cholesterol. LFDs may offer advantages because they provide easily administered, complete, balanced nutrition without affecting satiety.

During the past few years, considerable attention has been given to the impact of nutrition on kidney disease. The question arises of whether the effect of a moderate dietary protein restriction could be reinforced by enrichment of the diet with fermentable carbohydrates. Feeding fermentable carbohydrates may stimulate the extrarenal route of nitrogen (N) excretion through the fecal route. Such an effect has been reported in several species, including healthy humans and patients with chronic renal failure (CRF). Furthermore, studies of these subjects show that the greater fecal N excretion during the fermentable carbohydrate supplementation period was accompanied by a significant decrease in plasma urea concentration. In animal models of experimental renal failure, the consumption of diets containing fermentable carbohydrates results in a greater rate of urea N transfer from blood to the cecal lumen, where it is hydrolyzed by bacterial urease before subsequent microflora metabolism and proliferation. Therefore, this results in a greater fecal N excretion, coupled with a reduction in urinary N excretion and plasma urea concentration. Because elevated concentrations of serum urea N have been associated with adverse clinical symptoms of CRF, these results suggest a possible usefulness of combining fermentable carbohydrates with a low-protein diet to increase N excretion through the fecal route. Further investigations in this population of patients of whether fermentable carbohydrates in the diet may be beneficial in delaying or treating the symptoms and chronic complications of CRF will certainly emerge in the future. This should be realized without adversely affecting nutritional status and, as far as possible, by optimizing protein intake for the patients without being detrimental to renal function.

Several antioxidants inhibit atherosclerosis. This study investigated the hypothesis that combining vitamin E, a lipophilic antioxidant, with vitamin C, a hydrophilic antioxidant, and/or selenium, a cofactor of peroxidases that detoxify lipid peroxides, would inhibit atherosclerosis more effectively than vitamin E alone. We also considered whether regional variation in inhibition of atherosclerosis by antioxidants would be associated with regional variation in aortic lipophilic antioxidants. Rabbits were fed an atherogenic diet (control) or an atherogenic diet supplemented with vitamin E, vitamins E and C, vitamin E+selenium, vitamins E and C+selenium, or probucol (positive control). Supplements were as follows: vitamin E, 146 IU/d; vitamin C, 791 mg/d; selenium, 22 microg/d; or probucol, 406 mg/d. Vitamin C did not influence atherosclerosis. After 22 weeks of treatment, rank order of aortic atherosclerosis was control>vitamin E (with or without vitamin C)>vitamin E+selenium (with or without vitamin C)>probucol. Antioxidant treatment reduced aortic cholesterol concentrations 21% to 56%, 29% to 86%, and 19% to 75% for the aortic arch, descending thoracic aorta, and abdominal aorta, respectively (P<0.025 to P<0.0003 by ANOVA), with slightly greatly reductions for areas of atherosclerotic lesions. Some treatments reduced plasma cholesterol concentrations, but none altered the distribution of cholesterol among lipoproteins. Corrected for differences in plasma cholesterol concentrations, aortic cholesterol concentrations were reduced up to 72% (P<0.02) by the antioxidant treatments, with equal reductions by vitamin E+selenium and by probucol. Aortic alpha-tocopherol standardized by aortic cholesterol as a measure of aortic lipids was lower in the abdominal aorta than in the aortic arch of rabbits not given alpha-tocopherol and increased relatively more in the abdominal aorta than in the aortic arch with alpha-tocopherol supplementation. The results of this study suggest that vitamin E+ selenium inhibited atherosclerosis as effectively as an equally hypocholesterolemic dose of probucol by a mechanism(s) that is in part independent of effects on plasma and lipoprotein cholesterol concentrations. The tendency for greater efficacy of antioxidant treatments in the abdominal aorta than aortic arch may relate to the lower concentrations of alpha-tocopherol in the abdominal aorta of unsupplemented rabbits.

The effect of dietary guar gum (GG, 7.5%) on lipid metabolism and on bile acid secretion and reabsorption was investigated in rats adapted to cholesterol-free or 0.3% cholesterol diets. Compared with controls (fiber-free/cholesterol-free), rats fed cholesterol had significantly elevated plasma and liver cholesterol and triglyceride. In these rats, GG had a potent plasma cholesterol-lowering effect and also counteracted the liver accumulation of triglyceride and cholesterol esters. Fecal excretion of sterols, the major route of cholesterol elimination, was markedly enhanced by GG, especially in rats fed the cholesterol-containing diet (P < 0.001). The biliary bile acid flux into the small intestine was enhanced by dietary cholesterol (+30%) or GG (+52%) or both (P < 0.001). The fecal excretion of bile acids was significantly elevated by GG alone (+74%) and by dietary cholesterol (+190%). Small intestine reabsorption of bile acids appears to be significantly enhanced by GG, which also enhanced the transfer of bile acids into the large intestine, hence a greater fecal loss of steroids, although bile acid reabsorption was very effective in the cecum. GG feeding induced liver hydroxymethyl-glutaryl coenzyme A (HMG CoA) reductase, even in cholesterol-fed rats, as well as cholesterol 7 alpha-hydroxylase (P < 0.001). The cholesterol-lowering effect of GG thus appears to be mediated by an accelerated fecal excretion of steroids and a rise in the intestinal pool and biliary production of bile acids. Although liver HMG CoA reductase and cholesterol 7 alpha-hydroxylase are induced in parallel, this is not sufficient to compensate for fecal steroid losses.

The effects of consuming a liquid formula containing either fish oil enriched in omega-3 fatty acids or vegetable oil enriched in oleic acid was evaluated in 20 male subjects randomly allocated into two groups over a 42-d period. A decrease in collagen-induced aggregation by using washed platelet suspensions was found in both groups after nutritional supplementation. A considerable rise in omega-3 and a decrease in omega-6 fatty acids occurred in the platelet phospholipid with fish-oil consumption. The degree of eicosapentaenoic acid (EPA, 20:5n-3) enrichment (fish-oil group) was dramatically greater in the ether-containing plasmenylethanolamine (13.5 mol% of fatty acids; mol% of fatty acids = moles per 100 moles of total fatty acids) than in phosphatidylethanolamine (2.8 mol%) or phosphatidylcholine (2.9 mol%). Neither treatment significantly influenced the agonist-induced accumulation of lysoplasmenylethanolamine as derived via phospholipase A2 hydrolysis of plasmenylethanolamine. HPLC measurements of eicosanoid production in A23187-stimulated neutrophils revealed a considerable decrease in the formation of arachidonic acid-derived leukotriene B4 (LTB4), by 41%, and 5-HETE (5-hydroxyeicosatetraenoic acid), by 30%, in the fish-oil group along with the appearance of the corresponding EPA-derived products [LTB5 and 5-HEPE (5-hydroxyeicosapentaenoic acid)]. No such alterations in the formation of lipoxygenase products were found with the vegetable oil treatment.

The effect of different polysaccharides fermented in the large intestine and liable to lower plasma cholesterol was investigated in rats. Male rats were assigned to one of five treatment groups: control diet or a diet containing pectin, guar gum, gum arabic or beta-cyclodextrin. The four compounds were effectively fermented, yielding cecal short-chain fatty acids (SCFA) concentrations in the range of 130 to 170 mmol/L. Relative to controls, the cecal concentration of propionate was significantly higher in rats fed all fibers, especially those fed guar gum (+190%) or beta-cyclodextrin (+385%). All the fermented carbohydrates elicited a significant cholesterol-lowering effect, which was most potent in rats fed guar gum or beta-cyclodextrin, the two fibers that also significantly depressed plasma triglycerides. These two carbohydrates significantly lowered LDL and HDL1 cholesterol, triglyceride-rich lipoprotein triglycerides and apolipoprotein E levels. Apolipoprotein B was lowered only by beta-cyclodextrin. The microsomal activities of hydroxymethylglutaryl (HMG) CoA reductase and of cholesterol 7 alpha-hydroxylase were markedly elevated in rats fed guar gum or beta-cyclodextrin and, to a lesser extent, in those fed pectin compared with controls. Increased bile acid excretion seems to be essential in the cholesterol-lowering effect of soluble fibers and related compounds. This effect is connected to induction of HMG CoA reductase and lowering concentrations of apolipoprotein E-containing particles.

This study was conducted to study digestion in rats of a diet containing soybean fiber (chiefly hemicellulose). The animals were first fed a fiber-free high starch diet for 7 d before receiving a 30% soybean fiber diet. There was a progressive change in the cecal pool of volatile fatty acids (VFA), up to approximately 1000 mumol, due to the enlargement of the cecum in conjunction with the rise of the VFA concentration, and the decrease in the cecal pH to 6. In rats fed the soybean fiber diet, the cecal concentrations of acetate and propionate increased with propionate reaching a very high value (approximately 50 mmol/L) after 22 d of dietary treatment. Butyrate concentrations first increased, then declined to about 10 mmol/L. Absorption of VFA was enhanced fivefold between d 2 and d 21 and was then 10-fold higher than in rats fed the fiber-free diet. The transfer of blood urea to the cecum increased in parallel with the enlargement of the cecum and there was a large rise of ammonia absorption after 8 d. There was a rapid increase in the cecal pool of phosphorus, whereas the cecal pools of calcium and magnesium significantly increased only after 8 d. The cecal absorption of calcium and magnesium increased very early, even when the cecal pool of these cations was not enhanced. The soybean fiber diet also elicited a strong induction of ornithine decarboxylase (ODC) in cecal mucosa, which was attenuated after 21 d of dietary treatment. Thymidine kinase was smaller than for ODC.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of activation on lipid and lipoprotein metabolism were examined in resident murine macrophages, inflammatory cells elicited by thioglycolate, primed cells elicited by pyran copolymer, and activated cells elicited by Corynebacterium parvum. Low density lipoprotein receptors were reduced by 70%, while scavenger receptors were reduced 60% in activated cells. Basal cholesteryl ester and triglyceride synthesis were increased fourfold in activated cells, whereas the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase was high in resident cells and progressively declined by greater than 80% in activated cells. Activities of neutral cholesteryl esterase and neutral triglyceride lipase were increased two- to fourfold in inflammatory, primed, and activated macrophages. These results demonstrate the diverse changes in lipid and lipoprotein metabolism that occur with activation and emphasize how the behavior of macrophages in atherosclerotic lesions can be altered by activation.

The regulation of the secretion of lipoprotein lipase was studied in primary cultures of mouse peritoneal macrophages and in the murine macrophage cell line J774. As previously reported, both cell types secrete a lipase with the characteristics of lipoprotein lipase. Incubation of macrophages with insulin, insulin-like growth factor, and L-thyroxine had no effect on lipoprotein lipase secretion. Incubation with dexamethasone and with several agents which increase intracellular cyclic AMP led to a decrease in lipoprotein lipase secretion by mouse peritoneal macrophages. These results suggest that the hormonal regulation of lipoprotein lipase in macrophages is different from that in adipose tissue and heart muscle. Incubation of the macrophages with heparin caused a marked increase in the secretion of lipoprotein lipase. Short incubations with heparin (5 min) caused a release of the enzyme into the media, while longer incubations caused a 2-8-fold increase in net lipoprotein lipase secretion which was maximal after 2-16 h depending on cell type, and persisted for 24 h. The effect of heparin was dose-dependent and specific (it was not duplicated by other glycosaminoglycans). The mechanism of heparin-induced increase in lipoprotein lipase secretion was explored. The increase was not caused by the release of a presynthesized intracellular pool of lipoprotein lipase or by the stabilization of lipoprotein lipase by heparin after secretion. The heparin-induced increase in lipoprotein lipase secretion was dependent on protein synthesis. The secretion of lipoprotein lipase by macrophages in response to low levels of heparin may be a significant factor in the formation of atherosclerotic lesions.

The effects of ligand binding to the scavenger receptor on the secretion of lipoprotein lipase by murine macrophages were examined. Inflammatory macrophages exposed to acetylated low-density lipoprotein (AcLDL) exhibited a dose-dependent, 40-80% increase in lipoprotein lipase secretion. This stimulation appeared to be unrelated to intracellular cholesterol and triacylglycerol levels and to phagocytosis in general. Resident and inflammatory macrophages treated with maleylated bovine serum albumin (Mal-BSA) showed a 3-fold increase in lipoprotein lipase secretion in a dose-dependent and time-dependent fashion. In contrast, dextran sulfate, which is another ligand recognized by the scavenger receptor, caused a dose-dependent decrease in lipoprotein lipase secretion. Casein, a ligand recognized by the Mal-BSA receptor, did not affect lipoprotein lipase secretion nor the ability of Mal-BSA to stimulate the enzyme, while dextran sulfate abolished the stimulatory effects of Mal-BSA. Since ethylamine, an inhibitor of receptor-mediated endocytosis, attenuated the increase in lipoprotein lipase secretion induced by AcLDL and Mal-BSA, but did not affect the inhibition induced by dextran sulfate, it is suggested that receptor-mediated endocytosis of ligands via the scavenger receptor might play a key role in the stimulation of lipoprotein lipase secretion in macrophages. This study reveals another mechanism for regulation of macrophage lipoprotein lipase secretion.