The effect of malonyl-coa on fatty acid oxidation in rat muscle and liver mitochondria

The effect of malonyl-CoA on palmitate oxidation was compared for skeletal muscle and liver mitochondria from fed rats and rats starved for 18 and 42 h. The nutritional state did not influence the palmitate oxidation rate by both types of mitochondria. Muscle mitochondria are more sensitive to malonyl-CoA inhibition of palmitate oxidation than are liver mitochondria. Their response is not influenced by the nutritional state, in contrast to that of liver mitochondria. The extent of inhibition was not dependent on the carnitine concentration (above 0.5 mM), but higher at lower palmitate:albumin ratio or palmitate concentration.     

Effects of a fatty acid deficiency on lipids of whole brain, microsomes, and myelin in the rat

The lipid compositions of whole brain homogenates and microsomal and myelin fractions isolated from the brains of 6-month-old rats raised on a lab chow diet, a fatty acid-deficient diet, and a deficient diet supplemented with 5% (w/w) corn oil were determined. Brain and body weights were significantly lower in the fatty acid-deficient group. The compositions of alk-1-enyl groups and phospholipids of whole brain homogenates of rats maintained on the three diets were not different. However, marked alterations were found in the acyl group compositions of the major phosphoglycerides from whole brain homogenates and from the myelin and microsomal fractions of rats maintained on the fatty acid-deficient diet. With the deficient diet, 20:3(n - 9) was found in the major phosphoglycerides as well as in the myelin and microsomal fractions. In addition, the levels of 20:4(n - 6) and 22:4(n - 6) were decreased. The levels of 20:4(n - 6), 22:4(n - 6), and 22:5(n - 6) were higher in the brain phosphoglycerides of rats maintained on the corn oil-supplemented diet than on the lab chow control diet, and the elevation in these acyl groups was more evident in the microsomal fraction than in the myelin fraction.     

Effect of diet on fatty acid compositions in Sciaenops ocellatus

The role of dietary polyunsaturated fatty acids (PUFAs) on the fatty acid composition of juvenile red drum Sciaenops ocellatus was investigated. Individuals (n = 435) were fed three natural diets (Gulf menhaden Brevoortia patronus, brown shrimp Farfantapenaeus aztecus and Atlantic brief squid Lolliguncula brevis) that had significantly different proximate composition, energy density and PUFA compositions for 40 days. Diets were characterized as containing: high lipid, high protein, high energy and low PUFA (fish‐based), low lipid, low protein, low energy, moderate PUFA (shrimp‐based), and low lipid, high protein, moderate energy and high PUFA levels (squid‐based), respectively. Specimens were collected at days 0, 5, 10, 20 and 40 to evaluate rate of dietary fatty acid composition in tissues. Two‐source mixing models were used to calculate dietary fatty acid accumulation in consumer tissues. Results indicated that juvenile red drum incorporated an average of 35% dietary PUFAs after 5 days. Although relative biomass and dietary proximate composition had an effect upon the dietary fatty acid contribution, red drum averaged 91% incorporation of the five most prevalent PUFAs [18 : 2 (n ? 6), 20 : 4 (n ? 6), 20 : 5 (n ? 3), 22 : 5 (n ? 3) and 22 : 6 (n ? 3)] across all diets after 40 days. Growth varied as a function of diet and rates were higher for individuals fed the squid diet than those fed shrimp or fish diets primarily due to increased levels of protein and PUFAs [including 22 : 6 (n ? 3); 25·8%] in the diet. Red drum fed squid exhibited the greatest increase in average dietary fatty acid contribution by day 5, a trend that continued for the duration of the experiment. Since PUFA composition in red drum was significantly influenced by diet in as few as 5 days and almost completely incorporated into body tissues after 40 days, results from this study support the premise that fatty acids (especially PUFAs) are promising dietary indicators and may be useful for future studies examining trophic relationships of estuarine and marine fishes.     

Changes in fatty acid compositions of mitochondria during embryonic development

1. A general trend among biomembranes of hepatocytes in the developing avian embryo is to display increasing percentages of unsaturated fatty acids, especially oleic acid (C18:1). 2. However, once increasing amounts of thyroxine appear in the plasma, mitochondria begin to exhibit increasing percentages of saturated fatty acids, primarily stearic acid (C18:0). 3. Increasing saturation of mitochondrial membrane lipids can be inhibited by exposure of embryonated eggs to 500 R of X-irradiation. 4. Injection of embryonated eggs with estrone increases the proportion of oleic acid (C18:1) in mitochondrial membranes but a balancing increase in palmitic acid (C16:0) enables their lipids to remain more saturated than unsaturated.     

Diabetes-induced abnormalities of mitochondrial function in rat brain cortex: the effect of n-3 fatty acid diet

High expression of connexins was found in a variety of cancers, but their role is still controversial. We investigated whether connexin43 (Cx43) contributed to bladder carcinogenesis through MAPK activation. In this study, we found that Cx43 expression was significantly increased in bladder cancer tissues and cell line. Overexpression of Cx43 in bladder cancer 5637 cells increased cell proliferation, promoted cell cycle progression, and inhibited apoptosis. Western blot showed that JNK and ERK pathways were dramatically activated in Cx43-overexpressed cells. Conversely, knockdown of Cx43 inhibited cell proliferation by increasing apoptosis and causing cell cycle arrest, concomitant with inhibition of JNK and ERK signaling. In addition, JNK and ERK pathways were also activated in bladder cancer tissues. In conclusion, abnormal high expression and cytoplasmic localization of Cx43 contributed to bladder cancer. Inhibition of Cx43 activity could be a potential therapeutic strategy for preventing the progression of bladder cancer.     

Phospholipids and their fatty acids in mitochondria, synaptosomes and myelin from the liver and brain of trout and rat: a new view on the role of fatty acids in membranes

The content of different phospholipids (PL) and their fatty acid (FA) composition in subcellular fractions from the liver and brain of rat (Rattus rattus) and trout (Salmo irideus) were estimated. It was shown that despite higher content of unsaturated fatty acids in myelin compared to synaptosomes, the unsaturation index of the latter is equal or higher than that of myelin. The total content of PL polyunsaturated fatty acids (PUFA) was shown to be higher in membrane structures with more active ion transport (mitochondria). This feature seemed to be characteristic of membranes from both representatives of homoiotherms and poikilotherms studied. A possible role for PUFA information within the lipid monolayer of areas with different capacity to accept electrons and transport them along a sort of intermolecular 'tunnel' is discussed. The double bonds of PUFA in this area seem to be able to produce bonds similar to conjugated bonds.     

Regulation of fatty acid beta-oxidation in rat heart mitochondria

In an attempt to elucidate the mechanism by which the rate of fatty acid oxidation is tuned to the energy demand of the heart, the effects of changing intramitochondrial ratios of [acetyl-CoA]/[CoASH] and [NADH]/[NAD+] on the rate of beta-oxidation were studied. When 10 mM L-carnitine was added to coupled rat heart mitochondria to lower the ratio of [acetyl-CoA]/[CoASH], the rate of palmitoylcarnitine beta-oxidation, as measured by the formation of acid-soluble products, was stimulated more than fourfold at state 4 respiration while beta-oxidation at state 3 respiration was hardly affected. Neither oxaloacetate nor acetoacetate, added to mitochondria to lower the [NADH]/[NAD+] ratio, stimulated beta-oxidation. Rates of respiration at states 3 and 4 were unchanged by additions of L-carnitine, oxaloacetate, or acetoacetate. Determinations of intramitochondrial ratios of [acetyl-CoA]/[CoASH] by high performance liquid chromatography yielded values close to 10 for palmitoylcarnitine-supported respiration at state 4 and 2.5 at state 3 respiration. Addition of 10 mM L-carnitine caused a dramatic decrease of these ratios to less than 0.2 at both respiration states. Studies with purified or partially purified enzymes revealed strong inhibitions of 3-ketoacyl-CoA thiolase by acetyl-CoA and of L-3-hydroxyacyl-CoA dehydrogenase by NADH. Moreover, the activity of 3-ketoacyl-CoA thiolase at concentrations of acetyl-CoA and CoASH prevailing at state 3 respiration was 4 times higher than its activity in the presence of acetyl-CoA and CoASH observed at state 4. Altogether, this study leads to the conclusion that the rate of beta-oxidation in heart can be regulated by the intramitochondrial ratio of [acetyl-CoA]/[CoASH] which reflects the energy demand of the tissue. The thiolytic cleavage catalyzed by 3-ketoacyl-CoA thiolase may be the site at which beta-oxidation is controlled by the [acetyl-CoA]/[CoASH] ratio.     

Dexamethasone treatment in the newborn rat: fatty acid profiling of lung, brain, and serum lipids.

Dexamethasone is used as treatment for a variety of neonatal syndromes, including respiratory distress. The present study utilized the power of comprehensive lipid profiling to characterize changes in lipid metabolism in the neonatal lung and brain associated with dexamethasone treatment and also determined the interaction of dexamethasone with hypoxia. A 4-day tapering-dose regimen of dexamethasone was administered at 0800 on postnatal days 3 (0.5 mg/kg), 4 (0.25 mg/kg), 5 (0.125 mg/kg), and 6 (0.05 mg/kg). A subgroup of rats was exposed to hypoxia from birth to 7 days of age. Dexamethasone treatment elicited numerous specific changes in the lipid profile of the normoxic lung, such as increased concentrations of saturated fatty acids in the phosphatidylcholine and cholesterol ester classes. These increases were more profound in the lungs of hypoxic pups. Additional increases in cardiolipin concentrations were also measured in lungs of hypoxic pups treated with dexamethasone. We measured widespread increases in serum lipids after dexamethasone treatment, but the effects were not equivalent between normoxic and hypoxic pups. Dexamethasone treatment in hypoxic pups increased 20:4n6 and 22:6n3 concentrations in the free fatty acid class of the brain. Our results suggest that dexamethasone treatment in neonates elicits specific changes in lung lipid metabolism associated with surfactant production, independent of changes in serum lipids. These findings illustrate the benefits of dexamethasone on lung function but also raise the potential for negative effects due to hyperlipidemia and subtle changes in brain lipid metabolism.     

The effect of essential fatty acid deficiency upon fatty acid uptake by the brain.

Young adult rats, either control or essential fatty acid deficient, were administered either [3-H] oleic acid or [3-H] arachidonic acid by stomach tube. In addition, a group of control rats was given [3-H] palmitic acid. The rats were killed at various times therafter, and the radioactivity of the lipids of brain and plasma was examined. In confirmation of previous work, the blood lipid label was found to rise rapidly and then fall, wheras the activity of brain lipids increased slowly and did not show a decline through the 24-h period studied. Analysis of the brain uptake data according to first-order kinetics confirmed the impressions gained from visual inspection of the data. The initial rate of uptake of arachidonic acid was about 4.5 times that of oleic acid in control animals and in deficient animals. Essential fatty acid deficiency, however, did not induce an altered rate of uptake for either oleic acid or arachidonic acid. The rate of uptake of palmitic acid by control rats was not significantly different from that of oleic acid. Even though the initial rates of incorporation of oleic and arachidonic acids were not changed during essential fatty acid deficiency, the final levels of radioactivity obtained in brain lipids were higher in deficient rats with both fatty acids. The plateau value obtained with oleic acid was 1.5 times higher in deficient animals, while the plateau value for arachidonic acid was 1.7 times higher. An experiment in which deficient animals were allowed access to a control diet for 12 or 24 h prior to the labeling experiment suggested that the higher levels of radioactivity found in brain lipids of deficient animals was not due to an isotope dilution effect. Such animals still displayed the labeling pattern of deficient animals with arachidonic acid, while the results with oleic acid varied somewhat. Our results suggest that essential fatty acid deficiency does not alter the ability of the brain to take up the fatty acids studied. However, the fatty acids, especially arachidonic, are retained in the brain to a greater extent in the deficient animals.     

Changes in fatty acid composition of human brain myelin lipids during maturation

Abstract— The variation with age of the fatty acid composition of the major lipids in human brain myelin was compared with that of cerebral white matter from the same region. The myelin was isolated from the semiovale centre of the cerebrum of 27 subjects neonatal to old aged. The phospholipid, cholesterol and galactolipid concentrations were determined in all the samples, as were the proportions of the major phospholipid classes. The proportions of cholesterol and especially of the galactolipids increased in myelin during the first 6 months, and in cerebral white matter up to 2 years. During this period the individual phospholipids also varied substantially. Serine phosphoglycerides and especially sphingomyelins increased, and choline phosphoglycerides decreased. The fatty acid patterns of ethanolamine phosphoglycerides (EPG) and sphingomyelins underwent the largest changes. The proportions of saturated fatty acids in EPG diminished rapidly, and there was an increase of monoenoic acids. Fatty acids of the linoleic acid series showed a peak between 4 and 12 months, after which time their proportion slowly diminished to old age. The major fatty acid of this series was docosatetraenoic acid, 22:4 (n-6), which constituted more than 25% of total fatty acids at the maximum level. The fatty acid changes were larger in cerebral white matter, but from 2 years of age the EPG fatty acid pattern in myelin was similar to that in white matter. The fatty acid changes in serine and choline phosphoglycerides of myelin with maturation were much less striking than in EPG but of a similar type. In myelin sphingomyelin the proportion of saturated long-chain fatty acids, C₁₆-C₂₂, diminished, while that of monoenoic acids increased and continued to do so up to old age. From 2 years of age the fatty acid patterns in myelin and cerebral white matter were quite similar. Also the fatty acid patterns of cerebrosides and sulphatides in cerebral white matter and myelin were the same except for the first 2 months of life. The same fatty acid changes occurred in cerebrosides and sulphatides as in the sphingomyelins, i.e. increased proportions of unsaturated (monoenoic) acids. The proportions of 24:1 and 24h:1 and of the odd-numbered fatty acids 25:1 and 23h:1 continued to increase to old age. The variations of the individual lipid fatty acid patterns were small except in the youngest age classes, in which the variations were presumably ascribable to the difficulty in determining the gestational age.