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Effects of marine oil diet on peroxisomes and mitochondria of rat liver. A combined biochemical and morphometric study.

Feeding male rats a high cal% partially hydrogenated marine oil diet induced a response in the parenchymal liver cells at the cellular as well as the subcellular level. An adaptation in the lipid metabolism is indicated by an accumulation of triglycerides and a hypertrophy of the liver cells, and a rather selective increase (4.9-fold) in the specific activity of peroxisomal beta-oxidation. In addition, a slight proliferation of peroxisomes was observed; the volume fraction and the total number of peroxisomes increased 1.5-fold. The peroxisomes, however, preserved the biochemical and morphological homogeneity characteristic of peroxisomes in normal controls. At the mitochondrial level, a gradual development of megamitochondria was observed as the principal morphological change, with a 1.6-fold increase in the average size. The functional significance of this change remains to be determined. The effects of a partially hydrogenated marine oil diet on parenchymal liver cells appears to be manifestations with multiple causal factors. The high content of very long-chain trans fatty acids is of particular significance for the peroxisomal changes. An essential fatty acid deficiency, enforced by the presence of trans fatty acids in the diet, is most likely the determining factor for the development of megamitochondria.

3-Hydroxyacyl CoA Dehydrogenases↗

Factors affecting conjugated linoleic acid and trans-C18:1 fatty acid production by mixed ruminal bacteria.

The objective of this study was to identify environmental factors that influence conjugated linoleic acid (CLA) and trans-C18:1 fatty acid production by mixed ruminal bacteria. Ruminal contents were collected from a 600-kg ruminally fistulated Hereford steer maintained on pasture. Mixed ruminal bacteria were obtained by differential centrifugation under anaerobic conditions and added to a basal medium that contained a commercial emulsified preparation of soybean oil and a mixture of soluble carbohydrates (cellobiose, glucose, maltose, and xylose). Culture samples were collected from batch culture incubations at 0, 2, 4, 6, 8, 12, 24, 26, 28, 30, 32, and 48 h. Continuous culture incubations were conducted at dilution rates of 0.05 and 0.10 h(-1) with extracellular pH values of 5.5 and 6.5, and 0.5 and 1.0 g/L of mixed soluble carbohydrates. Culture samples were obtained from the culture vessel once steady-state conditions had been achieved. In batch culture, trans-C18:1 concentrations increased over time and reached a maximum at 48 h. Little CLA was produced during the first 8 h, but cis-9, trans-11 CLA concentrations remained high between 24 and 30 h. When mixed ruminal bacteria were maintained in continuous culture on 0.5 g/L of mixed soluble carbohydrates, concentrations of trans-C18:1 and cis-9, trans-11 CLA were reduced (P < 0.05) at a dilution rate of 0.05 h(-1) and an extracellular pH of 5.5. Similar effects were also observed when 1.0 g/L of mixed soluble carbohydrates was used. When extracellular pH was lowered to 5.0, neither trans-C18:1 or CLA isomers were detected. In conclusion, our results suggest that culture pH appears to have the most influence on the production of trans-C18:1 and CLA isomers by mixed ruminal bacteria.

Animals↗

Isolation and characterization of the cis-trans-unsaturated fatty acid isomerase of Pseudomonas oleovorans GPo12.

Pseudomonas oleovorans contains an isomerase which catalyzes the cis-trans conversion of the abundant unsaturated membrane fatty acids 9-cis-hexadecenoic acid (palmitoleic acid) and 11-cis-octadecenoic acid (vaccenic acid). We purified the isomerase from the periplasmic fraction of Pseudomonas oleovorans. The molecular mass of the enzyme was estimated to be 80 kDa under denaturing conditions and 70 kDa under native conditions, suggesting a monomeric structure of the active enzyme. N-terminal sequencing showed that the isomerase derives from a precursor with a signal sequence which is cleaved from the primary translation product in accord with the periplasmic localization of the enzyme. The purified isomerase acted only on free unsaturated fatty acids and not on esterified fatty acids. In contrast to the in vivo cis-trans conversion of lipids, this in vitro isomerization of free fatty acids did not require the addition of organic solvents. Pure phospholipids, even in the presence of organic solvents, could not serve as substrate for the isomerase. However, when crude membranes from Pseudomonas or Escherichia coli cells were used as phospholipid sources, a cis-trans isomerization was detectable which occurred only in the presence of organic solvents. These results indicate that isolated membranes from Pseudomonas or E. coli cells must contain factors which, activated by the addition of organic solvents, enable and control the cis-trans conversion of unsaturated acyl chains of membrane phospholipids by the periplasmic isomerase.

Alcohols↗

Trans fatty intakes during pregnancy, infancy and early childhood.

All of the essential n-6 and n-3 fatty acids accumulated by the fetus must be derived by transfer from the maternal circulation, and ultimately must originate from the maternal diet. After birth, the breast-fed infant receives essential fatty acids via mother's milk, or human milk substitutes and later complementary foods. Trans fatty acids (TFA) may have adverse effects on growth and development through interfering with essential fatty acid metabolism, direct effects on membrane structures or metabolism, or secondary to reducing the intakes of the cis essential fatty acids in either mother or child. TFA are transported across the placenta and secreted in human milk in amounts that depend on the maternal dietary intake. Inverse associations have been shown between TFA and the essential n-6 and n-3 fatty acids in newborn infants, human milk and preschool children. This support the need to reduce industrially produced trans fatty acids (IP-TFA) and improve dietary fat quality, particularly by increasing intake of n-3 fatty acids.

Biological Transport, Active↗

A comparative study on the effect of cis (oleic, linoleic) and trans (elaidic, linoelaidic) fatty acids on the in vitro prostaglandin biosynthesis in human blood platelets from (1-14C) arachidonic acid.

Dietary fatty acids affect the synthesis and thus ultimate availability of prostaglandin precursors. During processing of edible fats a significant portion of the naturally occurring cis fatty acids is changed to the respective trans isomers. Trans fatty acids could have a wide variety of effects including their effect on prostaglandin synthesis. A comparative study on the effect of cis (oleic and linoleic) fatty acids and their corresponding trans isomers (elaidic and linoelaidic acids) on the in vitro prostaglandin biosynthesis in human blood platelets was made. Linoleic acid (0.5, 1.0 mM) showed the same effect on the various arachidonic acid (AA) metabolites as reported earlier by us, that is, increased generation of prostaglandins and thromboxanes and reduced amounts of HHT and HETE (26). Linoelaidic acid at these two concentrations had the same effect but to a lesser extent. Both linoleic and linoelaidic acids at 0.25 mM concentration reduced TxB2 formation. Oleic and elaidic acids (0.5, 1.0 mM) decreased the formation of TxB2 though not significantly. With oleic acid, the results in respect of other AA metabolites were similar to those reported by us earlier (26). MDA was reduced significantly in the presence of linoleic, linoelaidic and oleic acids; cis isomers being more effective. In the presence of linoleic and linoelaidic acids, prostaglandin endoperoxides were reduced significantly; there was no change in the presence of oleic and elaidic acids. Thus fatty acids seem to affect the platelet cyclo-oxygenase activity; this being more pronounced in the case of cis fatty acids compared to their trans isomers. Reduction in cyclo-oxygenase activity also depends upon the number of double bonds in the acids.

Arachidonic Acids↗

Unsaturated fatty acids and platelet aggregation: in vitro study.

The effects of several cis and two trans fatty acids (elaidic and linoelaidic acids) - sodium salt and also in free acid form - on ADP-induced platelet aggregation were studied. The effects of the cis and trans fatty acids (sod. salt) on collagen-induced aggregation were also examined. Besides, the effects of several cis fatty acids, including dihomo-gamma-linolenic acid, on arachidonic acid induced aggregation were examined. The results indicate that unsaturated fatty acids inhibit platelet aggregation induced by ADP and collagen. The unsaturated fatty acids, however, with most blood samples did not show any antiaggregation effect on arachidonic acid-induced aggregation. While showing an antiaggregation effect on collagen-induced aggregation and failing to do so on arachidonic acid-induced aggregation, this difference in the behaviour of the unsaturated fatty acids in the two aggregations can be explained on the basis of binding of exogenous test fatty acids to plasma proteins. The mechanism(s) by which unsaturated fatty acids, in general, may exert their antiaggregation effect is discussed.

Adenosine Diphosphate↗

Adipose tissue alpha-linolenic acid and nonfatal acute myocardial infarction in Costa Rica.

BACKGROUND: Alpha-linolenic acid may protect against cardiovascular disease. We examined the association between adipose tissue alpha-linolenic acid and nonfatal acute myocardial infarction (MI) in a population-based case-control study in Costa Rica. METHODS AND RESULTS: The 482 case patients with a first nonfatal acute MI and 482 population control subjects were matched by age, sex, and area of residence. Fatty acids were assessed by gas-liquid chromatography in adipose tissue samples collected from all subjects. ORs and 95% CIs were calculated from multivariate conditional logistic regression models. Subjects in the top quintiles of adipose tissue alpha-linolenic acid had a lower risk of MI than those in the lowest quintile: OR (95% CI), 1.00; 0.80 (0.52 to 1.24); 0.53 (0.34 to 0.82); 0.44 (0.28 to 0.67); and 0.37 (0.24 to 0.59); test for trend, P<0.0001. This association was strengthened after adjustment for established MI risk factors, including smoking, physical activity, income, and adipose tissue linoleic acid and trans fatty acids (OR for the top versus lowest quintile, 0.23; 95% CI, 0.10 to 0.50; test for trend, P<0.0001). Further adjustment for the intake of saturated fat, fiber, alcohol, and vitamin E did not change this association (OR for the top versus lowest quintile, 0.23; 95% CI, 0.10 to 0.55; test for trend, P<0.0001). CONCLUSIONS: The inverse association observed between alpha-linolenic acid and nonfatal acute MI suggests that consumption of vegetable oils rich in alpha-linolenic acid confers important protection against cardiovascular disease.

Adipose Tissue↗

Fatty acids and CHD.

During the last century much evidence has accumulated to suggest that from a public health perspective the type of fat is more important than the amount of fat. Saturated and trans-fatty acids increase and both n-6 and n-3 PUFA decrease the risk of CHD. Most of the knowledge about the effects of dietary fatty acids on CHD risk is based on observational studies and controlled dietary experiments with intermediate end points (e.g. blood lipoprotein fractions). Information from high-quality randomised controlled trials on fatty acids and CHD is lacking. The Netherlands Institute for Public Health has calculated the potential health gain that can be achieved if the fatty acid composition of the current Dutch diet is replaced by the recommended fatty acid composition. The recommendations of The Netherlands Health Council are: saturated fatty acids <10% energy intake; trans-fatty acids <1% energy intake; fish consumption (an indicator of n-3 PUFA) once or twice weekly. Implementation of this recommendation could reduce the incidence of CHD in The Netherlands by about 25,000/year and the number of CHD-related deaths by about 6000/year and increase life expectancy from age 40 years onwards by 0.5 year. These projections indicate the public health potential of interventions that modify the fatty acid composition of the diet.

Coronary Disease↗

A stearic acid-rich diet improves thrombogenic and atherogenic risk factor profiles in healthy males.

OBJECTIVE: To determine whether healthy males who consumed increased amounts of dietary stearic acid compared with increased dietary palmitic acid exhibited any changes in their platelet aggregability, platelet fatty acid profiles, platelet morphology, or haemostatic factors. DESIGN: A randomized cross-over dietary intervention. SUBJECTS AND INTERVENTIONS: Thirteen free-living healthy males consumed two experimental diets for 4 weeks with a 7 week washout between the two dietary periods. The diets consisted of approximately 30% of energy as fat (66% of which was the treatment fat) providing approximately 6.6% of energy as stearic acid (diet S) or approximately 7.8% of energy as palmitic acid (diet P). On days 0 and 28 of each dietary period, blood samples were collected and anthropometric and physiological measurements were recorded. RESULTS: Stearic acid was increased significantly in platelet phospholipids on diet S (by 22%), while on diet P palmitic acid levels in platelet phospholipids also increased significantly (8%). Mean platelet volume, coagulation factor FVII activity and plasma lipid concentrations were significantly decreased on diet S, while platelet aggregation was significantly increased on diet P. CONCLUSION: Results from this study indicate that stearic acid (19g/day) in the diet has beneficial effects on thrombogenic and atherogenic risk factors in males. The food industry might wish to consider the enrichment of foods with stearic acid in place of palmitic acid and trans fatty acids.

Adult↗

Comparative evaluation of rumen-protected fat, coconut oil and various oilseeds supplemented to fattening bulls. 2. Effects on composition and oxidative stability of adipose tissues.

The effects of five different dietary fat supplements on fatty acid composition and oxidative stability of subcutaneous and kidney fat were evaluated in 36 Brown Swiss bulls and compared to a low fat diet in a monofactorial design. The following fat supplements were provided as additional fat at 30 g per kg feed dry matter: crystalline rumen-protected fat, coconut oil, and three types of crushed whole oilseeds (rapeseed, sunflower seed and linseed). Adipose tissues reflected differences (P < 0.05) in dietary fatty acid composition although to a lower extent. Using protected fat, which contained elevated levels of trans fatty acids, and sunflower seed, containing a high proportion of linoleic acid, significantly increased C18:1 trans fatty acid proportion in the adipose tissues. The use of sunflower seed increased conjugated linoleic acid. The oilseeds resulted in lower amounts of C16:0 in favour of C18:0. Except for linseed, all fat supplemented groups improved oxidative stability of adipose tissues as compared with control. This was explained by lower proportions of unsaturated fatty acids in adipose tissue (protected fat), by elevated alpha-tocopherol contents (rapeseed, sunflower seed) or by a combination of both (coconut oil). Fat colour remained unaffected by treatments. Compared to other fat supplements oilseeds, especially sunflower seed and rapeseed, can therefore be recommended to be fed to bulls in order to increase the proportions of C18 unsaturated fatty acids in adipose tissues and to maintain or improve oxidative stability.

Adipose Tissue↗

Adipose fatty acids and cancers of the breast, prostate and colon: an ecological study. EURAMIC Study Group.

Animal and ecological studies suggest that linoleic acid intake is related to breast-cancer incidence. Analytical epidemiologic studies, however, do not support such findings. The primary objective of our ecological study was to investigate the association between breast-cancer incidence and linoleic acid status across European countries. In addition, other fatty acids and cancer sites were studied. Mean fatty acid composition of adipose tissue samples in 11 centres from 8 European countries and Israel served as indicators of exposure of the population. Figures on cancer incidence for the respective or comparable regions were obtained from published data. N-6 fatty acids in adipose tissue ranged from 10.4 in Helsinki to 24.6 g/100 g fatty acids in Jerusalem. N-6 fatty acids were not associated significantly with breast, colon or prostate cancer. Cancers of the breast and colon were associated negatively with cis-mono-unsaturated fatty acids and positively with trans fatty acids. Despite a large range in intake, we found no evidence of a positive association between n-6 fatty acid status and breast cancer, but associations were observed between other fatty acids and cancer. Differences in linoleic acid intake cannot explain risk differences in breast-cancer incidence between affluent countries, while associations of other fatty acids with cancer rates may reflect cultural differences.

Adipose Tissue↗

Evolutionary aspects of omega-3 fatty acids in the food supply.

Information from archaeological findings and studies from modern day hunter-gatherers suggest that the Paleolithic diet is the diet we evolved on and for which our genetic profile was programmed. The Paleolithic diet is characterized by lower fat and lower saturated fat intake than Western diets; a balanced intake of omega-6 and omega-3 essential fatty acids; small amounts of trans fatty acids, contributing less than 2% of dietary energy; more green leafy vegetables and fruits providing higher levels of vitamin E and vitamin C and other antioxidants than today's diet and higher amounts of calcium and potassium but lower sodium intake. Studies on the traditional Greek diet (diet of Crete) indicate an omega-6/omega-3 ratio of about 1/1. The importance of a balanced ratio of omega-6:omega-3, a lower saturated fatty acid and lower total fat intake (30-33%), along with higher intakes of fruits and vegetables leading to increases in vitamin E and C, was tested in the Lyon Heart study. The Lyon study, based on a modified diet of Crete, confirmed the importance of omega-3 fatty acids from marine and terrestrial sources, and vitamin E and vitamin C, in the secondary prevention of coronary heart disease, and cancer mortality.

Animals↗

Some Food and Drug Administration perspectives of fat and fatty acids.

Because of public health concerns about the amount of fat in the American diet, the Food and Drug Administration and the US Department of Agriculture have emphasized use of the recently reformed food label to inform consumers about the fat and fatty acid contents of foods. The health effects of specific fatty acids continue to be the subject of much research, discussion, and debate. Issues that must be addressed to further improve the communication effectiveness of the food label include health effects of n-3 and n-6 fatty acids; appropriate labeling of trans fatty acids, stearic acid, and other non-cholesterol-raising fatty acids; partially absorbed fats; and label claims, especially health claims, for specific fatty acids and fatty acids of biotechnologically altered foods.

Diet↗

Dietary stearic acid alters gallbladder bile acid composition in hamsters fed cereal-based diets.

Dietary stearic acid (18:0) lowers plasma and liver cholesterol concentration by reducing intestinal cholesterol absorption. We tested the hypothesis that dietary 18:0 reduces cholesterol absorption by altering hepatic bile acid synthesis and gallbladder bile acid composition. Male Syrian hamsters were fed modified NIH-07 open formula diets, enriched (5 g/100 g diet) in one of the following fatty acids: 18:0, palmitic acid (16:0), trans fatty acids (18:1t), oleic acid (18:1c) or linoleic acid (18:2). After 18 wk, gallbladders were removed and bile acid composition determined by HPLC. The distribution of primary bile acids (mol/100 mol) was unaffected by treatment. In contrast, dietary 18:0 significantly reduced the proportion of hydrophobic secondary bile acids, resulting in a lower hydrophobicity index of the bile. These data suggest that reduced cholesterol absorption by dietary 18:0 is due, at least in part, to reduced cholesterol solubility. The data further suggest that 18:0 may have altered the microflora populations that synthesize secondary bile acids. Although cholesterol 7alpha-hydroxylase (CYP7A1) activity was significantly higher in hamsters fed 18:0 compared with 16:0, this finding is most likely due to increased fecal bile acid output in the 18:0 group rather than transcriptional regulation of CYP7A1 by 18:0 or specific bile acids.

Animals↗

Antagonistic action of lipid components of membranes from Candida albicans and various other lipids on two imidazole antimycotics, clotrimazole and miconazole.

The growth-inhibitory activity of two imidazole antimycotics, clotrimazole and miconazole, against Candida albicans was significantly reversed when lipid extracts from protoplast membranes of the same organism were added to the assay medium together with the drugs. Of four major classes of lipids further separated from them, viz., phospholipids, triglycerides, sterol esters, and free sterols, the former two were capable of counteracting both drugs, whereas the latter two were not. However, even with phospholipids or triglycerides, no antagonism was noted when they were saturated by catalytic hydrogenation before use. The antagonistic effect of varying classes of commercial lipids, including phospholipids, acylglycerides, sterols, and fatty acids, was also studied by means of the agar diffusion technique. Significant antagonism to both drugs was observed with: (i) phospholipids with an unsaturated acyl group; (ii) acylglycerides, the ester portion of which consists of unsaturated fatty acid; (iii) ultraviolet-activated sterols; and (iv) unsaturated fatty acids of cis-configuration. By contrast, none of the saturated phospholipids and acylglycerides nor sterols was effective as an antagonist. With the exception only of lauric acid, all of a series of saturated fatty acids and unsaturated trans-fatty acids ranging from C(8) to C(18) in chain length were either minimally effective or completely ineffective. Essentially, there was no qualitative difference between clotrimazole and miconazole in the response to these various lipids.

Candida albicans↗

Dietary fat and incidence of type 2 diabetes in older Iowa women.

OBJECTIVE: To examine the associations between reported intakes of dietary fat and incident type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied the relation between dietary fatty acids and diabetes in a prospective cohort study of 35,988 older women who initially did not have diabetes. Diet was assessed with a food frequency questionnaire at baseline, and 1,890 incident cases of diabetes occurred during 11 years of follow-up. RESULTS: After adjusting for age, smoking, alcohol consumption, BMI, waist-to-hip ratio, physical activity, demographic factors, and dietary magnesium and cereal fiber, diabetes incidence was negatively associated with dietary polyunsaturated fatty acids, vegetable fat, and trans fatty acids and positively associated with omega-3 fatty acids, cholesterol, and the Keys score. After simultaneous adjustment for other dietary fat, only vegetable fat remained clearly related to diabetes risk. Relative risks across quintiles of vegetable fat intake were 1.00, 0.90, 0.87, 0.84, and 0.82 (P = 0.02). Diabetes risk was also inversely related to substituting polyunsaturated fatty acids for saturated fatty acids and positively correlated to the Keys dietary score. CONCLUSIONS: These data support an inverse relation between incident type 2 diabetes and vegetable fat and substituting polyunsaturated fatty acids for saturated fatty acids and cholesterol.

Age Factors↗

Dietary studies on two rural Italian population groups of the Seven Countries Study. 2. Concurrent validation of protein, fat and carbohydrate intake.

On 18 subjects from two rural areas in Italy which were part of the Seven Countries Study (Crevalcore and Montegiorgio), we carried out the concurrent validation of protein, fat, fatty acid and carbohydrate intake in the diet at the thirty-first year follow-up in 1991. The values of the above nutrients obtained using food composition tables from the weighted record method for dietary surveys were compared with the values from chemical analysis of food composites. In both areas for protein, fat and carbohydrate intake the inter-individual variation was large. For protein intake the mean difference was statistically significant but not for fat intake. From 1960 to 1991 protein and fat intake tended to decrease and for protein the means of differences between analysis and calculation were, in general, statistically different. For dietary saturated and polyunsaturated fatty acids, the means of differences were statistically significant in Crevalcore, but this was not the case in Montegiorgio for polyunsaturated fatty acids. The intake of trans fatty acids in both areas was rather low. Available and unavailable carbohydrate intake of both areas showed no statistically significant difference. The mean differences between analysis and calculation for both areas were statistically significant with the exception of cellulose in Crevalcore and sugars in Montegiorgio.

Adult↗

Production of butter fat rich in trans10-C18:1 for use in biomedical studies in rodents.

Trans fatty acids are suspected to be detrimental to health, particularly to cardiovascular function. Trans fatty acids include a wide range of fatty acids, with isomers of C18:1, conjugated and non-conjugated C18:2 as major components. A vaccenic acid (trans11-C18:1) + rumenic acid (cis9,trans11-CLA)-rich butter has been shown previously to exhibit health beneficial effects, but less is known concerning another trans-C18:1 present in hydrogenated vegetable oil-based products and sometimes in milk fat, the trans10-isomer. The present experiment was conducted to produce butters from milk of variable fatty acid composition for use in biomedical studies with rodents, with the overall aim of evaluating the specific effect of trans10-C18:1 and trans11-C18:1 + cis9,trans11-CLA on cardiovascular function. Milks from lactating dairy cows fed two types of maize-based diets supplemented (5% of dry matter)--or not--with sunflower oil were collected, and used to manufacture butters either rich in trans10-C18:1 (14% of total fatty acids, 64.5% of fat content) or rich in trans11-C18:1 + cis9,trans11-CLA (7.4 and 3.1% of total fatty acids, respectively, 68.5% of fat content), or with standard fatty acid composition (70% of fat content). Additionally, total saturated fatty acid percentage was reduced by more than one third in the enriched butters compared with the standard butter. An understanding of the role of nutrition on milk fatty acid composition in cows allows for the production of dairy products of variable lipid content and composition for use in biomedical studies in animal models and human subjects.

Animal Feed↗