Dichloroacetate improves cardiac efficiency after ischemia independent of changes in mitochondrial proton leak.

Dichloroacetate (DCA) is a pyruvate dehydrogenase activator that increases cardiac efficiency during reperfusion of ischemic hearts. We determined whether DCA increases efficiency of mitochondrial ATP production by measuring proton leak in mitochondria from isolated working rat hearts subjected to 30 min of ischemia and 60 min of reperfusion. In untreated hearts, cardiac work and efficiency decreased during reperfusion to 26% and 40% of preischemic values, respectively. Membrane potential was significantly lower in mitochondria from reperfused (175.6 +/- 2.2 mV) versus aerobic (185.8 +/- 3.1 mV) hearts. DCA (1 mM added at reperfusion) improved recovery of cardiac work (1.9-fold) and efficiency (1.5-fold) but had no effect on mitochondrial membrane potential (170.6 +/- 2.9 mV). At the maximal attainable membrane potential, O(2) consumption (nmol O(2) x mg(-1) x min(-1)) did not differ between untreated or DCA-treated hearts (128.3 +/- 7.5 and 120.6 +/- 7.6, respectively) but was significantly greater than aerobic hearts (76.6 +/- 7.6). During reperfusion, DCA increased glucose oxidation 2.5-fold and decreased H(+) production from glucose metabolism to 53% of untreated hearts. Because H(+) production decreases cardiac efficiency, we suggest that DCA increases cardiac efficiency during reperfusion of ischemic hearts by increasing the efficiency of ATP use and not by increasing the efficiency of ATP production.

Fatty acid composition and possible health effects of coconut constituents.

The link between excessive consumption of dietary saturated fats and coronary heart disease (CHD) is now well established. Because of its high content of saturated fatty acids, the consumption of foods containing coconut oil may therefore be a risk factor for CHD. While the fatty acid composition of coconut oil is well established, relatively little is known about the other constituents of coconut: the milk, water, cream and meat fractions. In this study, we show that while the water fraction is low in lipid content, the milk contains about 24% of the fat content of oil and the cream and meat fractions about 34%. The other coconut constituents contain significant amounts of medium-chain triglycerides that are formed from fatty acids of chain length 8:0 to 14:0. It is these fatty acids, primarily 14:0, that are thought to be atherogenic. On the other hand, medium-chain triglycerides may be advantageous under some circumstances in that they are absorbed intact and do not undergo degradation and re-esterification processes. As a result, medium-chain triglycerides provide a ready source of energy and may be useful in baby foods or in diet therapy. Nevertheless, the possible negative effects of the saturated fatty acids and the absence of the essential fatty acid linolenic acid from all coconut constituents suggest that the coconut milk, oil and cream should not be used on a regular basis in adults.

Fatty acid composition and possible health care effects of coconut constituents

The link between excessive composition of dietary saturated fats and coronary heart disease (CHD) is now well established. Because of its high content of saturated fatty acids, the composition of foods containing coconut oil may therefore be a risk factor for CHD. While the fatty acid composition of coconut oil is well established, relatively little is known about the other constituents of coconut: the milk, water, cream and meat fractions. In this study, we show that while the water fraction is low in lipid content, the milk contains about 24 percent of the fat content of oil and the cream and meat fractions about 34 percent. The other coconut constituents contain significant amounts of medium-chain triglycerides that are formed from fatty acids of chain length 8:0 to 14:0. It is these fatty acids, primarily 14:0, that are thought to be atherogenic. On the other hand, medium-chain triglycerides provide a ready source of energy and may be useful in baby foods or in diet therapy. Nevertheless, the possible negative effects of the saturated acids and the absence of the essential fatty acid linolenic acid from all coconut constituents suggest that the coconut milk, oil and cream should not be used on a regular basis in adults. (AU)

Fatty acid composition and possible health care effects of coconut constituents

The link between excessive composition of dietary saturated fats and coronary heart disease (CHD) is now well established. Because of its high content of saturated fatty acids, the composition of foods containing coconut oil may therefore be a risk factor for CHD. While the fatty acid composition of coconut oil is well established, relatively little is known about the other constituents of coconut: the milk, water, cream and meat fractions. In this study, we show that while the water fraction is low in lipid content, the milk contains about 24 percent of the fat content of oil and the cream and meat fractions about 34 percent. The other coconut constituents contain significant amounts of medium-chain triglycerides that are formed from fatty acids of chain length 8:0 to 14:0. It is these fatty acids, primarily 14:0, that are thought to be atherogenic. On the other hand, medium-chain triglycerides provide a ready source of energy and may be useful in baby foods or in diet therapy. Nevertheless, the possible negative effects of the saturated acids and the absence of the essential fatty acid linolenic acid from all coconut constituents suggest that the coconut milk, oil and cream should not be used on a regular basis in adults.

Thyroid hormone status and membrane n-3 fatty acid content influence mitochondrial proton leak.

Proton leak, as determined by the relationship between respiration rate and membrane potential, was lower in mitochondria from hypothyroid rats compared to euthyroid controls. Moreover, proton leak rates diminished even more when hypothyroid rats were fed a diet containing 5% of the lipid content as n-3 fatty acids. Similarly, proton leak was lower in euthyroid rats fed the 5% n-3 diet compared to one containing only 1% n-3 fatty acids. Lower proton leaks rates were associated with increased inner mitochondrial membrane levels of n-3 fatty acids and a decrease in the ratio of n-6/n-3 fatty acids. This trend was evident in the phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and cardiolipin phospholipid fractions. These results suggest that a significant portion of the effect of thyroid hormone status on proton leak is due to alterations in membrane fatty acid composition, primarily changes in n-3 content. Both the hypothyroid state and dietary effects appear to be mediated in part by inhibition of the Delta6- and Delta5-desaturase pathways.

Dietary n-3 fatty acids alter angiotensin-induced contraction and 1,2-diacylglycerol fatty acid composition in thoracic aortas from diabetic rats.

The effect of diabetes on the incorporation of long-chain n-3 fatty acids into thoracic aorta smooth muscle phospholipids and 1,2-diacylglycerol, and on the contractile response of aortic rings to angiotensin II, was examined in streptozotocin-induced diabetic rats. In diabetic animals fed a diet containing 1% of fatty acids as n-3 fatty acids, smooth muscle membrane levels of 18:2n-6 were elevated in phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, whereas 20:4n-6 was depleted. The resultant decreased ratios of 20:3/18:2 and 20:4/20:3 indicate inhibition of delta6- and delta5-desaturase activity in the diabetic state. A diet containing 5% of fatty acids as n-3 fatty acids increased phospholipid levels of eicospentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) several-fold, but with a further reduction in 20:4n-6. Similarly, 1,2-diacylglycerol from rats fed the high n-3 diet was enriched in EPA, DPA and DHA. When incubated with 10(-8) M angiotensin II, the contractile response of intact aortic rings from diabetic animals fed the high n-3 diet was only 60.8+/-9.3% that of controls fed the same diet. However, contractile response was not significantly different from control animals fed the low n-3 diet (55.6+/-7.9%). The results indicate that vascular smooth muscle phospholipid n-6 and n-3 fatty acid metabolism is altered in diabetes, resulting in changes to the fatty acid profile of 1,2-diacylglycerol. Moreover, elevating membrane phospholipid and 1,2-diacylglycerol content of EPA, DPA and DHA partially ameliorates the depressed response to angiotensin II seen in the diabetic state.

Hypothyroid state and membrane fatty acid composition influence cardiac mitochondrial pyruvate oxidation.

Pyruvate oxidation was measured in cardiac mitochondria from euthyroid and hypothyroid rats fed diets enriched with either omega-6 or omega-3 fatty acids. Both State 4 and State 3 rates of pyruvate-dependent respiration were markedly reduced in hypothyroid mitochondria, regardless of diet consumed, compared to euthyroid controls. Respiratory control ratios and ADP/O ratios were the same under all treatments. While there was no significant effect of diet on respiration in euthyroid mitochondria, pyruvate oxidation was 28% higher in hypothyroid mitochondria from animals fed the omega-3 diet compared to those fed the omega-6 diet. Depressed respiration in the hypothyroid state was correlated with 18% more phosphatidylcholine in the inner mitochondrial membrane whereas phosphatidylethanolamine was 17% lower and cardiolipin 32% lower compared to controls. The total phospholipid fatty acid composition was not affected by the hypothyroid state. However, enhanced respiration in hypothyroid animals fed the omega-3 diet was associated with a 3-fold increase in monounsaturated fatty acids in the cardiolipin fraction, and a 12-fold increase in omega-3 fatty acids, primarily 22:5(omega-3) and 22:6(omega-3). The data suggest that membrane levels of cardiolipin and its omega-3 fatty acid content modulate pyruvate transport in hypothyroid mitochondria.

Thyroid status and dietary fatty acids affect beta-adrenoceptor agonist stimulation of tension development in rat myocardium.

1. The inotropic responses to the beta-adrenoceptor agonists adrenaline, noradrenaline and isoprenaline were examined in papillary muscles isolated from hypothyroid rats and euthyroid controls that had been fed diets enriched in either n-6 or n-3 fatty acids. 2. In hypothyroid animals fed the n-6 diet, the maximum developed tension in the presence of isoprenaline was only 54% greater than resting tension compared to 160% in euthyroid animals. Maximum tension was 105% greater than resting in hypothyroid animals fed the n-3 diet compared to 399% in controls. Similar responses to adrenaline and noradrenaline were seen, i.e. maximum tension was significantly greater in both hypothyroid and euthyroid animals fed the n-3 diet, but tension was depressed in the hypothyroid state. 3. Binding of the beta-adrenoceptor antagonist [3H]-dihydroalprenolol to ventricular membranes was saturable and of high affinity, irrespective of thyroid state and diet. While binding site density (Bmax) was not affected by the hypothyroid state or diet, binding affinity (Kd) was higher in hypothyroid animals fed the n-6 diet. 4. The inotropic response to forskolin was the same in hypothyroid animals, irrespective of diet, but maximum developed tension was significantly greater in euthyroid animals fed the n-6 compared to the n-3 diet. The dose-response curve for forskolin was shifted to the right in hypothyroid animals fed the n-3 diet indicating a decrease in sensitivity. 5. These results indicate that the depressed contractility in the hypothyroid heart may be due in part to an altered lipid environment of the beta-adrenoceptor complex and that n-3 fatty acids can significantly increase maximum developed tension in the hypothyLroid state.

N-3 and N-6 fatty acids modulate the inotropic response to calcium in hypothyroid rat papillary muscle.

The calcium sensitivity of papillary muscles was enhanced at low [Ca2+] in euthyroid rats fed a diet enriched in n-3 fatty acids compared to rats fed diets high in n-6 and saturated (SAT) fatty acids. At the same time, the maximum developed tension was 44% lower in animals fed the n-3 diet compared to those fed the n-6 diet and 62% lower than the rats fed the SAT diet. In hypothyroid animals fed the n-3 diet, the inotropic response to added Ca2+ was only 60% of that in euthyroid controls and 50 and 65% of euthyroid controls in n-6 and SAT diet-fed animals, respectively. Although the response was again lower in n-3-fed animals, the differences among the diet treatments were not as great as those seen in euthyroid animals, and there were no apparent diet-dependent differences in sensitivity to Ca2+ in hypothyroid animals. The potency of the calcium-channel blocker nifedipine was diet-dependent in euthyroid animals, with the order of decreasing sensitivity being n-3 > n-6 > SAT. Papillary muscles were not as sensitive to nifedipine in hypothyroid animals, although n-3-fed animals again showed the greatest inhibition of tension development. On the other hand, nitrendipine-binding affinity was not different among euthyroid and hypothyroid animals fed the n-6 diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dietary lipid composition on rat liver microsomal phosphatidylcholine synthesis.

Effects of dietary lipid on microsomal membrane fatty acid composition and phosphatidylcholine synthesis were examined with respect to the degree of saturation and chain length of dietary fatty acids. Diets containing 20% fat (wt/wt), primarily in the form of coconut oil, beef tallow, or soybean oil were fed to weanling rats for 28 d. All diets were adequate in essential fatty acids. Feeding the coconut oil diet, containing more than 50% saturated medium-chain fatty acids, increased the long-chain omega 3 fatty acid levels and altered the ratio of omega 6 to omega 3 fatty acids in membrane phosphatidylcholine and phosphatidylethanolamine compared to that in animals fed diets containing a saturated tallow or polyunsaturated soybean oil diet. Change in membrane fatty acid composition in response to the coconut oil diet was accompanied by decreased synthesis of phosphatidylcholine via the cytidine diphosphate choline (CDP-choline) pathway, and increased synthesis via the phosphatidylethanolamine methyltransferase (PEMT) pathway. An overall decrease in phosphatidylcholine production was reflected in a lower ratio of phosphatidylcholine to phosphatidylethanolamine in the membrane. Modulation of hepatic phosphatidylcholine synthesis during early growth thus appears to be in response to the ratio of long-chain omega 6 fatty acids to omega 3 fatty acids in membrane phospholipid rather than levels of specific fatty acids or the relative degree of saturation of fatty acids in the diet.

Calorimetric and spectroscopic studies of lipid thermotropic phase behavior in liver inner mitochondrial membranes from a mammalian hibernator.

Arrhenius plots of various enzyme and transport systems associated with the liver mitochondrial inner membranes of ground squirrels exhibit changes in slope at temperatures of 20-25 degrees C in nonhibernating but not in hibernating animals. It has been proposed that the Arrhenius breaks observed in nonhibernating animals are the result of a gel to liquid-crystalline phase transition of the mitochondrial membrane lipids, which also occurs at 20-25 degrees C, and that the absence of such breaks in hibernating animals is due to a major depression of this lipid phase transition to temperatures below 4 degrees C. In order to test this hypothesis, we have examined the thermotropic phase behavior of liver inner mitochondrial membranes from hibernating and nonhibernating Richardson's ground squirrels, Spermophilus richardsonii, by differential scanning calorimetry and by 19F nuclear magnetic resonance and fluorescence polarization spectroscopy. Each of these techniques indicates that no lipid phase transition occurs in the membranes of either hibernating or nonhibernating ground squirrels within the physiological temperature range of this animal (4-37 degrees C). Moreover, differential scanning calorimetric measurements indicate that only a small depression of the lipid gel to liquid-crystalline phase transition, which is centered at about -5 degrees C in nonhibernating animals and at about -9 degrees C in hibernators, occurs. We thus conclude that the Arrhenius plot breaks observed in some membrane-associated enzymatic and transport activities of nonhibernating animals are not the result of a lipid phase transition and that a major shift in the gel to liquid-crystalline lipid phase transition temperature is not responsible for seasonal changes in the thermal behavior of these inner mitochondrial membrane proteins.

Characterization of the phospholipid and fatty acid composition of Sendai virus.

The lipid composition of Sendai virus, propagated in chicken eggs, was analyzed by high performance liquid chromatography (HPLC), thin-layer chromatography (TLC), and gas-liquid chromatography (GLC). Phosphatidylcholine was found to be the dominant phospholipid (37.3%) with phosphatidylethanolamine (26.8%) and phosphatidylserine (12.0%) also present in significant amounts. Analysis of the fatty acid methyl esters revealed that the dominant fatty acids in total phospholipid were: C16:0 (17.6%), C18:0 (15.4%), C18:1 (n-9) (22.0%), and C24:0 (6.0%). Cardiolipin, phosphatidylserine, and sphingomyelin contained higher levels of saturated fatty acids relative to phosphatidylinositol, phosphatidylethanolamine, and phosphatidylcholine.