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PubMed2002

Mitochondrial factors in the pathogenesis of diabetes: a hypothesis for treatment.

A growing body of evidence has demonstrated a link between various disturbances in mitochondrial functioning and type 2 diabetes. This review focuses on a range of mitochondrial factors important in the pathogenesis of this disease. The mitochondrion is an integral part of the insulin system found in the islet cells of the pancreas. Because of the systemic complexity of mitochondrial functioning in terms of tissue and energetic thresholds, details of structure and function are reviewed. The expression of type 2 diabetes can be ascribed to a number of qualitative or quantitative changes in the mitochondria. Qualitative changes refer to genetic disturbances in mitochondrial DNA (mtDNA). Heteroplasmic as well as homoplasmic mutations of mtDNA can lead to the development of a number of genetic disorders that express the phenotype of type 2 diabetes. Quantitative decreases in mtDNA copy number have also been linked to the pathogenesis of diabetes. The study of the relationship of mtDNA to type 2 diabetes has revealed the influence of the mitochondria on nuclear-encoded glucose transporters and the influence of nuclear encoded uncoupling proteins on the mitochondria. This basic research into the pathogenesis of diabetes has led to the awareness of natural therapeutics (such as coenzyme Q10) that increase mitochondrial functioning and avoidance of trans-fatty acids that decrease mitochondrial functioning.

Adenosine Triphosphate↗
PubMedDate not supplied

[New Nordic nutrition recommendations 2004. Physical activity as important as good nourishing food].

The 4th edition of the Nordic Nutrition Recommendations (NNR 2004) now includes detailed recommendations on daily physical activity. For adults a minimum of 30 minutes of daily physical activity of moderate intensity and/or vigorous intensity is recommended. More physical activity (about 60 minutes daily) may be needed for prevention of weight gain. For children a minimum of 60 minutes of physical activity every day is recommended. As in the 3rd edition, a limitation of the intake of saturated plus trans fatty acids to about 10 % of the total energy intake (E%) and of the total fat intake to 30 E% is recommended. The intake of carbohydrates and dietary fibre should increase, while the intake of refined sugars should not exceed 10 E%. The 4th edition includes changes in the recommended intakes for e.g. vitamin A, D and C and for folate.

Adolescent↗
PubMed2006

[Lifestyle to prevent cardiovascular disease in NIDDM].

Major risk factors for cardiovascular diseases (myocardial infarction, angina pectoris, brain infarction) are age, male, smoking, high LDL-cholesterol, low HDL-cholesterol, high blood pressure, and diabetes mellitus. In Japanese population at large, healthy life-style to prevent cardiovascular diseases are; quit smoking, walking faster, saturated fat intake ranging 4.5-7 en%, lesser intake of trans fatty acids, cholesterol intake less 750 mg/day (male) and 600 mg/day (female), eat fish everyday, eat more folic acid, B6, and B12, eat grain, eat soybean products. However, it is not known whether this recommendation is also applied to NIDDM to prevent cardiovascular diseases. Based on reported evidences, to prevent cardiovascular diseases, NIDDM should quit smoking, eat fish everyday, and increase physical activity.

Arteriosclerosis↗
PubMed1987

Dietary fat and breast cancer.

This paper reviews the relationship between dietary fat and breast cancer. The incidence of breast cancer is discussed with regard to dietary habits, geographic location, and economic status. The roles of Trans-fatty acids and urinary as well as plasma estrone, estradiol (E2), estriol (E3), and estrogen are reviewed. Specific hypotheses are proposed to explain the relationship between fatty acid intake and breast cancer.

Breast Neoplasms↗
PubMed1995

Optimal diet for reducing the risk of arteriosclerosis.

The primary objectives of current dietary advice for those at risk from coronary artery disease (CAD) focus on progressive restriction of dietary saturated (and trans) fatty acids and cholesterol intake, combined with exercise and achievement of ideal body weight. These principles are endorsed by the official bodies of most western nations concerned with reducing CAD mortality and have recently been reaffirmed by the Adult Treatment Panel of the National Cholesterol Education Program. There has been concern, however, in view of the increasing use of drug therapy, that additional strategies should supplement the primary goals to increase the palatability and effectiveness of the diet. These additional strategies include increased intake of foods high in soluble viscous fibres, vegetable proteins, possibly antioxidants such as vitamin E and the isoflavonoids, increased intake of alpha-linolenic acid and, for those with low high density lipoprotein cholesterol levels, increased monounsaturated fat intake. These strategies translate into advice to significantly increase consumption of specific plant foods such as green leafy vegetables, nuts and seeds, and dried legumes, all of which improve the overall nutritional quality of the diet and contain specific active ingredients. These changes represent a regression to a more primitive diet on the evolutionary scale.

Adult↗
PubMedDate not supplied

Optimizing lipid levels through diet.

Medical nutrition therapy, consisting of a diet low in saturated fat, has an important role in reducing risks for cardiovascular disease and hyperlipidemia. Dietary factors that have a negative effect on blood lipid levels include dietary cholesterol, saturated fat, and trans fatty acids, whereas unsaturated fats, omega-3 fatty acids, and soluble fiber may help lower blood lipid levels. A two-step approach to medical nutrition therapy can help health professionals counsel people with high lipid levels to change their food choices and eating behaviors to lower their risk of heart disease. This approach involves teaching the patient how to substitute lower-fat foods, read labels, control portions, and use healthier cooking techniques. Medical nutrition therapy needs to be individualized to help lower the risk of heart disease.

Cardiovascular Diseases↗
PubMed1998

[Hyperlipidemia in children and adolescents: diagnosis and therapy].

Severe hyperlipidemias should be diagnosed and treated even in childhood and adolescence, because vascular lipid deposition in the form of fatty streaks and progressive atherosclerotic lesions start to develop early in life. The heterozygous form of familial hypercholesterolemia found in about 1 of 500 newborn infants, and polygenic forms of hypercholesterolemia, are the most frequent forms of primary genetic hypercholesterolemia found in children. Secondary hyperlipidemias, e.g. in diabetes mellitus, hypothyroidism and renal disease, are relatively frequent in children and adolescents and need to be searched for in the diagnostic evaluation, because they can be influenced by treatment of the underlying disorder. Children and adolescents with severe forms of hyperlipidemias should be diagnosed and treated early in life. Dietary modification is the basis of treatment of affected children and can lower LDL cholesterol by about 15-20%. In patients with severe hypercholesterolemia, dietary cholesterol intake should not exceed 150 mg/day in children or 250-300 mg/day in adolescents. Even more important is a reduction of the intake of saturated fats and trans fatty acids and their replacement by polyunsaturated and particularly monounsaturated fats. Some additional lowering of LDL cholesterol may be achieved by the preferential use of vegetable over animal proteins and of complex carbohydrates over sugars. Repeated motivation, counseling and intensive practical training of the patient and family, supported by appropriate teaching materials, are essential for effective dietary treatment. Additional drug treatment is considered in children from the age of 8-9 years of age onwards if, in spite of adequate dietary modification, LDL cholesterol remains above 190 mg/dl (4.9 mmol/l), or above 160 mg/dl (3.9 mmol/l) in the presence of additional risk factors. The drugs of first choice are anion exchange resins (colestyramine or colestipol) because of their well documented efficacy and safety. More convenient to take but often somewhat less effective is beta-sitosterol. If efficacy or compliance with resins or sitosterin is unsatisfactory, fibrates (e.g. bezafibrate, fenofibrate) may be considered as a drug of second choice. Cholesterol synthesis inhibitors are not recommended for general use in children at this time.

Adolescent↗
PubMed2004

Carbon isotope fractionation during cis-trans isomerization of unsaturated fatty acids in Pseudomonas putida.

The molecular mechanism of the unique cis to trans isomerization of unsaturated fatty acids in the solvent-tolerant bacterium Pseudomonas putida S12 was studied. For this purpose, the carbon isotope fractionation of the cis-trans isomerase was estimated. In resting cell experiments, addition of 3-nitrotoluene for activation of the cis-trans isomerase resulted in the conversion of the cis-unsaturated fatty acids into the corresponding trans isomers. For the conversion of C16:1 cis to its corresponding trans isomer, a significant fractionation was measured. The intensity of this fractionation strongly depended on the rate of cis-trans isomerization and the added concentration of 3-nitrotoluene, respectively. The presence of a significant fractionation provides additional indication for a transition from the sp carbon linkage of the cis-double bond to an intermediate sp3 within an enzyme-substrate complex. The sp2 linkage is reconstituted after rotation to the trans configuration has occurred. As cytochrome c plays a major role in the catabolism of Cti polypeptide, these findings favour a mechanism for the enzyme in which electrophilic iron (Fe(3+)), provided by a heme domain, removes an electron of the cis double bond thereby transferring the sp2 linkage into sp3.

Binding Sites↗
PubMed1999

The effect of palm oil, lard, and puff-pastry margarine on postprandial lipid and hormone responses in normal-weight and obese young women.

Only a few studies have been published on the postprandial effects of different fatty acids in obese subjects. Therefore, the present study investigated the effects of three test meals containing palm oil (PO), lard (LD), or puff-pastry margarine (PPM), all normal dietary ingredients, on postprandial lipid and hormone responses in normal-weight and obese young women. The study was performed as a randomized, crossover design. The fats differed in the content of palmitic acid, stearic acid, and trans monounsaturated fatty acids allowing a dietary comparison of different 'solid' fatty acids. The obese women had significantly higher fasting concentrations and postprandial responses of plasma total triacylglycerol (TAG), chylomicron-TAG, and insulin compared with the normal-weight women but there was no significant difference in the postprandial responses between the three test meals. The obese women had fasting concentrations of leptin four times greater than the normal-weight women. There were no postprandial changes in the concentrations of leptin. The fasting concentrations of HDL-cholesterol were significantly lower in the obese women than in the normal-weight women, whereas there was no significant difference between the two groups in the concentrations of total cholesterol or LDL-cholesterol. These results provide evidence that obese women have exaggerated lipid and hormone responses compared with normal-weight women but the different contents of saturated and trans monounsaturated fatty acids provided by PO, LD, and PPM have no effect in either group.

Adult↗
PubMed1994

Dietary and ruminally derived trans-18:1 fatty acids alter bovine milk lipids.

The objectives of this study were to determine whether dietary fish oil enhances production of trans-18:1 isomers in the bovine rumen and whether flow of ruminally derived and/or dietary trans-18:1 to the small intestine is correlated with milk fat production. Four lactating Holstein cows with cannulas in the rumen and proximal duodenum were fed diets with 0% supplemental fat (control diet), 3% hydrogenated tallow fatty acids (HTFA diet), 1.5% menhaden oil plus 1.5% stearic acid (MO+SA diet), or 1.5% soybean oil plus 1.5% partially hydrogenated soybean oil (SBO+HSBO diet) in a 4 x 4 Latin square design. Intakes of trans-18:1 were 0, 12, 0 and 69 g/d when cows were fed the control, HTFA, MO+SA and SBO+HSBO diets, respectively. However, the extent of 18:1 + 18:2(n-6) + 18: 3(n-3) biohydrogenation in the rumen was reduced by consumption of the MO+SA and SBO+HSBO diets. As a result, flow of trans-18:1 to the duodenum was 163 g/d for MO+SA-fed cows and 152 g/d for SBO+HSBO-fed cows compared with 38 g/d for cows fed the HTFA and control diets. Incomplete biohydrogenation accounted for all of the trans-18:1 flow when the MO+SA diet was fed. Compared with results when the HTFA and control diets were fed, milk fat percentage was lower and concentration of trans-18:1 in milk fat was higher when the MO+SA and SBO+HSBO diets were fed. Across all treatments, milk fat percentage decreased linearly with the amount of trans-18:1 flowing to the duodenum and the concentration of trans-18:1 in milk fat. Results indicate that bovine milk fat percentage is depressed by trans-18:1, whether derived from the diet or from incomplete biohydrogenation of unsaturated fatty acids.

Animals↗
PubMed1997

Linoleic and alpha-linolenic acids differently modify the effects of elaidic acid on polyunsaturated fatty acid metabolism and some immune indices in rats.

To explore whether the metabolic responses to trans, compared with cis, fatty acids depend on the source of dietary polyunsaturated fatty acids (PUFA), male Sprague-Dawley rats, 5 weeks old, were fed on diets containing 30 g oleic (cis) or elaidic (trans) acids/kg in combination with either 70 g perilla oil (alpha-linolenic acid) or safflowerseed oil (linoleic acid)/kg for 3 weeks in separate experiments. The dietary fats were adjusted to have the same level of total PUFA. The dietary manipulation did not influence the growth indices, but spleen weight was greater when the dietary PUFA source was perilla oil. The incorporation of trans fatty acid into liver phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine and adipose tissue lipids, particularly phospholipids, was significantly higher when rats were fed on safflowerseed oil compared with perilla oil. However, only limited differences were observed in the effects of cis and trans fatty acids on the proportions of PUFA in liver phospholipids. Splenic production of prostaglandin E2 was reduced by trans fatty acid when safflowerseed oil was the PUFA source, but no trans effect was observed on leukotriene C4 production. Dietary PUFA significantly influenced the concentration of plasma immunoglobulins (Ig) but the effect of geometry was only seen in IgG which was increased by trans acid. Dietary trans fatty acid increased the CD4+:CD8+ T-lymphocyte ratio in the spleen, reflecting a decreasing trend of the proportion of CD8+, when combined with perilla oil. These observations indicate that the type of PUFA simultaneously ingested specifically influences the effect that trans acid exerts on PUFA metabolism, eicosanoid production and some immune indices.

Animals↗
PubMedDate not supplied

Determination of trans unsaturation by infrared spectrophotometry and determination of fatty acid composition of partially hydrogenated vegetable oils and animal fats by gas chromatography/infrared spectrophotometry: collaborative study.

An infrared spectrophotometric (IR) method for the determination of total trans unsaturated fatty acid (trans) content and a combined gas-liquid chromatographic/infrared spectrophotometric (GC/IR) method for determination of fatty acid composition of partially hydrogenated vegetable oils (PHVO) were studied collaboratively in 12 laboratories using 7 PHVO samples, including 1 pair of blind duplicates. The test samples were methylated and analyzed for total trans content by IR and for fatty acid composition by GC/IR using a capillary column coated with SP-2560 or another suitable cyanoalkylsiloxane stationary phase. From the measured IR absorption, the isolated trans content was calculated using a calibration curve of absorption versus trans content developed with 2-component calibration standard mixtures of methyl elaidate and oleate. The GC provided the levels of mono-trans-octadecadienoates (18:2t), di-trans-octadecadienoates (18:2tt) and mono-trans-octadecatrienoates (18:3t). The trans-octadecenoate (18:1t) content was calculated with the formula: 18:1t = IR trans-0.84 x (18:2t + 18:3t) - 1.74 x 18:2tt. The cis-octadecenoate (18:1c) content was obtained as the difference between total octadecenoates (18:1) and 18:1t. Reproducibility relative standard deviations (RSDR) for 15 to 35% trans content determined by IR were in the range of 8.8-11.7%, whereas RSDR for the test sample with 5% trans content was 34.6%. RSDR values for 18:1t by the GC/IR followed the same pattern as that of IR trans values: 36.4% for the test sample with 4.9% 18:1t versus 7.8-12.5% for test samples with 14.9 to 32.6% 18:1t. The content of 18:1c in the test samples varied from 24.7 to 34.5% and their RSDR values ranged from 3.8 to 10.5%. The mean values for 18:1t and 18:1c compared favorably with the absolute levels determined by a silver nitrate-thin layer chromatography/GC procedure. The IR and GC/IR methods are recommended for determination of trans content and fatty acid composition, respectively, of partially hydrogenated fats derived from vegetable oils, terrestrial animal fats or such oils and fats isolated from food products containing > 5% trans fatty acids. For samples containing < or = 5% trans fatty acids, a direct GC method (American Oil Chemists' Society Official Method Ce 1c-89) is available for determination of both trans content and fatty acid composition, because at lower trans levels, overlap of 18:1 cis and trans isomers on GC with very polar capillary columns is negligible.(ABSTRACT TRUNCATED AT 400 WORDS)

Chromatography, Gas↗
PubMed2003

Mechanism of cis-trans isomerization of unsaturated fatty acids in Pseudomonas putida.

We studied the pattern of the cis-trans isomerization of unsaturated fatty acids in cells of Pseudomonas putida S12 grown in a medium supplemented with oleic acid which was deuterated at both of the C atoms of its double bond. Direct evidence that isomerization does not include a transient saturation of the double bond was obtained. In addition, analysis of the amino acid sequences of the seven known Cti proteins identified them as heme-containing proteins of the cytochrome c type.

Bacterial Proteins↗
PubMed1988

The role of unnatural dietary trans and cis unsaturated fatty acids in the epidemiology of coronary artery disease.

During 1956 the first report on the hypocholesterolemic effect of unsaturated fatty acids of plant and marine origin was published in The Lancet. Consequently it was stated in a Lancet Editorial that hydrogenation of vegetable oils could have contributed to the causation of coronary artery disease and predicted that a decade would probably be required to resolve this question. However, after the lapse of three decades this issue would appear to be no nearer to a clear answer now than it was then. During 1956 hydrogenation was assumed to effect only a reduction in the level of unsaturated fatty acids in the products produced from hydrogenated oils. However, since that time essential fatty acid metabolic pathways to eicosanoids were discovered and described. Also large quantities of unnatural trans and cis unsaturated fatty acids have been shown to form during hydrogenation and these occur in margarines and many other common foods in high concentrations. It has also been shown that these unnatural trans and cis fatty acids block essential fatty acid metabolism by the competitive inhibition of the desaturase enzyme delta-6-desaturase. Therefore some of the possible metabolic mechanisms whereby "hydrogenation plants could have contributed to the causation of a major disease" have become clearer during the last three decades. Despite a recent conclusion by an ad hoc FDA panel that there need be little concern about the effects of trans fatty acids in the American diet on health, it is nevertheless proposed that on the basis of available evidence, unnatural dietary trans and cis unsaturated fatty acid isomers should be regarded as a definite risk factor in the etiology of coronary artery disease.

Coronary Disease↗
PubMed1985

The effects of exposure to exogenous fatty acids and membrane fatty acid modification on the electrical properties of NG108-15 cells.

The role of membrane lipid composition in determining the electrical properties of neuronal cells was investigated by altering the available fatty acids in the growth medium of cultured neuroblastoma X glioma hybrid cells, clone NG108-15. Growth of the cells for several days in the presence of polyunsaturated fatty acids (linoleic, linolenic, and arachidonic) caused a pronounced decrease in the Na+ action-potential rate of rise (dV/dt) and smaller decreases in the amplitude, measured by intracellular recording. Oleic acid had no effect on the action potentials generated by the cells. In contrast, a saturated fatty acid (palmitate) and a trans monounsaturated fatty acid (elaidate) caused increases in both the rate of rise and the amplitude. No changes in the resting membrane potentials or Ca2+ action potentials of fatty acid-treated cells were observed. The membrane capacitance and time constant were not altered by exposure to arachidonate, oleate, or elaidate, whereas arachidonate caused a small increase in membrane resistance. Examination of the membrane phospholipid fatty acid composition of cells grown with various fatty acids revealed no consistent alterations which could explain these results. To examine the mechanism for arachidonate-induced decreases in dV/dt, the binding of 3H-saxitoxin (known to interact with voltage-sensitive Na+) channels was measured. Membranes from cells grown with arachidonate contained fewer saxitoxin binding sites, suggesting fewer Na+ channels in these cells. We conclude that conditions which lead to major changes in the membrane fatty acid composition have no effect on the resting membrane potential, membrane capacitance, time constant, or Ca2+ action potentials in NG108-15 cells. Membrane resistance also does not appear to be very sensitive to membrane fatty acid composition. However, changes in the availability of fatty acids and/or changes in the subsequent membrane fatty acid composition lead to altered Na+ action potentials. The primary mechanism for this alteration appears to be through changes in the number of Na+ channels in the cells.

Action Potentials↗
PubMed1998

Modulation of K+ channels by arachidonic acid in T84 cells. I. Inhibition of the Ca(2+)-dependent K+ channel.

The Cl- secretory response of colonic cells to Ca(2+)-mediated agonists is transient despite a sustained elevation of intracellular Ca2+. We evaluated the effects of second messengers proposed to limit Ca(2+)-mediated Cl- secretion on the basolateral membrane, Ca(2+)-dependent K+ channel (Kca) in colonic secretory cells, T84. Neither protein kinase C (PKC) nor inositol tetrakisphosphate (1,3,4,5 or 3,4,5,6 form) affected Kca in excised inside-out patches. In contrast, arachidonic acid (AA; 3 microM) potently inhibited Kca, reducing NP0, the product of number of channels and channel open probability, by 95%. The apparent inhibition constant for this AA effect was 425 nM. AA inhibited Kca in the presence of both indomethacin and nordihydroguaiaretic acid, blockers of the cyclooxygenase and lipoxygenase pathways. In the presence of albumin, the effect of AA on Kca was reversed. A similar effect of AA was observed on Kca during outside-out recording. We determined also the effect of the cis-unsaturated fatty acid linoleate, the trans-unsaturated fatty acid elaidate, and the saturated fatty acid myristate. At 3 microM, all of these fatty acids inhibited Kca, reducing NP0 by 72-86%. Finally, the effect of the cytosolic phospholipase A2 inhibitor arachidonyltrifluoromethyl ketone (AACOCF3) on the carbachol-induced short-circuit current (Isc) response was determined. In the presence of AACOCF3, the peak carbachol-induced Isc response was increased approximately 2.5-fold. Our results suggest that AA generation induced by Ca(2+)-mediated agonists may contribute to the dissociation observed between the rise in intracellular Ca2+ evoked by these agonists and the associated Cl- secretory response.

Arachidonic Acid↗