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Dependence with nutritional status of the ethanol effects on fatty acid metabolism in rat hepatocytes.

1. The effects of ethanol on fatty acid synthesis, esterification and oxidation were studied in hepatocytes isolated from fed and 24 hr fasted rats. 2. [3H]H2O was preferentially incorporated into the glycerol backbone of triglycerides and phospholipids. Addition of ethanol markedly increased the incorporation of this label in both classes of glycerolipids; the increase was higher in fasted rat hepatocytes, both in the glycerol backbone and acyl groups of glycerolipids. 3. Ethanol increased [U-14C]palmitate incorporation into triglycerides only in hepatocytes from fasted rats. 4. [14C]CO2 and total acid soluble product formation from [1-14C]palmitate resulted inhibited by ethanol both in the fed and the fasted state.

Animals↗

Discrepancies between myocardial perfusion and free fatty acid metabolism in patients with hypertrophic cardiomyopathy.

To test the hypothesis that there are discrepancies between 201Tl- and 123I-beta-methylpentadecanoic acid (BMIPP) distribution in the left ventricular myocardium and to assess whether BMIPP is a useful tracer agent for the assessment of left ventricular function in hypertrophic cardiomyopathy (HCM), myocardial single photon emission computed tomography (SPECT) was performed with 201Tl and BMIPP in five normal subjects and 12 patients with asymmetric septal hypertrophy. Tracer uptake in the left ventricular myocardium was scored using a four-point grading system. A homogenous distribution of the tracer with no discrepancy between 201Tl and BMIPP uptake in the left ventricular myocardium was observed in each normal subject. In contrast, BMIPP uptake was reduced compared to 201Tl in 58 segments (40%) of the 144 myocardial segments in patients with HCM. Such discordant BMIPP uptake was observed in 15 segments (42%) of the septal segments, in 19 segments (53%) of the anterior segments, in eight segments (22%) of the lateral segments, and in 16 segments (44%) of the inferior segments. There was no significant correlation between 201Tl perfusion score and left ventricular ejection fraction, whereas there was a significant correlation between BMIPP perfusion score and left ventricular ejection fraction (r = 0.748; P < 0.01). The results indicated that there were discrepancies between 201Tl and BMIPP uptake in a significant proportion of myocardial segments, suggesting the impairment of fatty acid metabolism and that BMIPP is a useful tracer agent for the assessment of left ventricular function in hypertrophic cardiomyopathy.

Cardiomyopathy, Hypertrophic↗

CO2-mediated control of fatty acid metabolism in isolated hamster brown-fat cells during norepinephrine stimulation.

1. Addition of norepinephrine to isolated hamster brown-fat cells suspended in Krebs-Ringer phosphate buffer induces a pronounced, but temporary increase in respiratory rate. 2. If Krebs-Ringer phosphate buffer is bubbled with CO2 prior to the addition of cells and norepinephrine, the respiratory capacity of the cells is further potentiated and most important, the respiration is maintained at a high rate until the medium becomes depleted of oxygen. 3. This respiratory pattern cannot be obtained in CO2-bubbled Krebs-Ringer bicarbonate buffer. 4. The results indicate that CO2 has a regulatory effect on fatty acid metabolism in isolated hamster brown-fat cells.

Adenosine Diphosphate↗

Effect of hippurate on tissue fatty acid metabolism.

The authors studied 1-14C-palmitate metabolism in rat muscle, renal cortex and liver incubated with synthetic hippurate in vitro (1 mmol/l). a) Hippurate did not affect 1-14C-palmitate uptake and utilization in the muscle (hemidiaphragm). b) In the renal cortex it stimulated only the incorporation into total lipids and from the individual lipid fractions into mono- and diglycerides and free fatty acids (FFA). c) In the liver it stimulated the uptake, oxidation to 14CO2 and incorporation into total lipids and, out of the individual lipid fractions, into phospholipids, triacylglycerols and free fatty acids. d) Hippurate already had a significant effect in the concentration of 0.5 mmol/l, i.e. during the development of the disturbance and not just as a supplementary factor in advanced renal insufficiency. It is concluded that, by interfering with fatty acid metabolism, the hippurate present in the serum of patients with renal insufficiency plays an active role in the development of dyslipoproteinaemia in such patients.

Animals↗

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↗

No indications for altered essential fatty acid metabolism in two murine models for cystic fibrosis.

A deficiency of essential fatty acids (EFA) is frequently described in cystic fibrosis (CF), but whether this is a primary consequence of altered EFA metabolism or a secondary phenomenon is unclear. It was suggested that defective long-chain polyunsaturated fatty acid (LCPUFA) synthesis contributes to the CF phenotype. To establish whether cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction affects LCPUFA synthesis, we quantified EFA metabolism in cftr-/-CAM and cftr+/+CAM mice. Effects of intestinal phenotype, diet, age, and genetic background on EFA status were evaluated in cftr-/-CAM mice, DeltaF508/DeltaF508 mice, and littermate controls. EFA metabolism was measured by 13C stable isotope methodology in vivo. EFA status was determined by gas chromatography in tissues of cftr-/-CAM mice, DeltaF508/DeltaF508 mice, littermate controls, and C57Bl/6 wild types fed chow or liquid diet. After enteral administration of [13C]EFA, arachidonic acid (AA) and docosahexaenoic acid (DHA) were equally 13C-enriched in cftr-/-CAM and cftr+/+CAM mice, indicating similar EFA elongation/desaturation rates. LA, ALA, AA, and DHA concentrations were equal in pancreas, lung, and jejunum of chow-fed cftr-/-CAM and DeltaF508/DeltaF508 mice and controls. LCPUFA levels were also equal in liquid diet-weaned cftr-/-CAM mice and littermate controls, but consistently higher than in age- and diet-matched C57Bl/6 wild types. We conclude that cftr-/-CAM mice adequately absorb and metabolize EFA, indicating that CFTR dysfunction does not impair LCPUFA synthesis. A membrane EFA imbalance is not inextricably linked to the CF genotype. EFA status in murine CF models is strongly determined by genetic background.

Animals↗

Training and fatty acid metabolism.

Older studies in humans seem to suggest a correlation between plasma long chain fatty acid (LCFA) turnover and oxidation on the one hand and plasma LCFA concentration on the other hand during submaximal exercise. However, recent studies in man, in which higher concentrations of plasma LCFA have been reached during prolonged submaximal exercise, have revealed a levelling off in net uptake in spite of increasing plasma LCFA concentrations. Furthermore, this relationship between plasma LCFA concentration and plasma LCFA uptake and oxidation was altered by endurance training such that levelling off was not apparent in the trained state. These recent findings in man give support to the notion from other cell types that transport of fatty acids from the vascular compartment to the cytosolic space in the muscle cell is not only due to simple diffusion, but is predominantly carrier-mediated. During prolonged submaximal knee-extension exercise it has been demonstrated that the total oxidation of LCFA was approximately 60% higher in trained compared to nontrained subjects. The training-induced adaptations responsible for this increased utilization of plasma fatty acids by the muscle could be located at several steps from the mobilization of fatty acids to skeletal muscle metabolism in the mitochondria. To what extent triacylglycerol located in the muscle cell contribute to the overall lipid utilisation during exercise is still not clear. However, due to underestimation of the contribution of plasma LCFA and fatty acids liberated from the circulating VLDL-triacylglycerols to the overall fatty acid oxidation during exercise there is increasing understanding that muscle triacylglycerol contributes to a lesser extent as fuel during exercise in man than mostly stated.

Exercise↗

A study of the fatty acid metabolism of the yeast Pityrosporum ovale.

The yeast Pityrosporum ovale, a skin saprophyte, will only grow if fatty acids of chain length greater than C(10) are added to the culture medium. 9-Hydroxypalmitic acid is the major product of metabolism of even-carbon-number fatty acids; 9-hydroxystearic acid is also found. The optimum pH for this conversion is pH4.5. The hydroxy fatty acids produced are found bound in a polar form in the aqueous phase of the culture medium. Growth of the organisms is facilitated by presentation of the substrate as a two-phase liquid system.

Chromatography, Gas↗

Metabolic changes in hibernating myocardium after percutaneous transluminal coronary angioplasty and the relation between recovery in left ventricular function and free fatty acid metabolism.

To elucidate the changes in oxidative metabolism in hibernating myocardium after coronary revascularization, we performed myocardial single-photon emission computed tomography with a free fatty acid analog, I-123 beta-methyliodophenylpentadecanoic acid (BMIPP), and thallium-201 before and 1 month after percutaneous transluminal coronary angioplasty (PTCA) in 11 patients with angina pectoris caused by single artery stenosis. All patients had improvement in wall motion after PTCA at the region with coronary stenosis; the wall motion abnormality score evaluated by left ventriculography decreased from 5.5+/-0.8 (mean +/- SE) to 2.1+/-0.9, p <0.01) after PTCA. The defect score of I-123 BMIPP images was significantly larger than that of thallium-201 images either before (14+/-1.3 vs 8.9+/-1.1, p <0.01) or 1 month after (7.4+/-1.5 vs 3.7+/-0.8, p <0.01) PTCA. The decrease in the defect score of both images was significant (p <0.01). Changes in the wall motion abnormality score showed a significant correlation with both the change in the defect score of thallium-201 images (r = 0.58, p < 0.01) and that of I-123 BMIPP images (r = 0.75, p <0.01). These results indicate that the metabolism of free fatty acid is impaired in hibernating myocardium, and that improvement in left ventricular function after successful PTCA is strongly associated with the recovery of oxidative metabolism.

Adult↗

Interactions between plasticizers and fatty acid metabolism in the perfused rat liver and in vivo. Inhibition of ketogenesis by 2-ethylhexanol.

Rates of ketone body (beta-hydroxybutyrate plus acetoacetate) production by perfused livers from starved rats were decreased about 60% from 39 +/- 2 to 17 +/- 3 mumol/g/hr by 2-ethylhexanol (200 microM), a primary metabolite of the plasticizer diethylhexyl phthalate. Inhibition of ketogenesis by ethylhexanol was dose dependent (half-maximal inhibition occurred with 25 microM) in the presence or absence of 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. Concentrations of beta-hydroxybutyrate relative to acetoacetate (B/A) increased in a step-wise manner from 0.32 to 0.75 in the effluent perfusate when ethylhexanol was infused. In contrast, the B/A ratio decreased in parallel with inhibition of ketone body production when alcohol dehydrogenase was inhibited. Pretreatment of rats with phenobarbital, an inducer of omega and omega-1 hydroxylases, diminished inhibition of ketone body production by low (less than 50 microM) of ethylhexanol. Thus, ethylhexanol is oxidized via phenobarbital-inducible pathways to metabolites which do not inhibit ketogenesis. Studies were conducted to determine the site of inhibition of fatty acid oxidation by ethylhexanol. Rates of ketone body production in the presence of oleate (250 microM), which requires transport of the corresponding CoA compound into mitochondria, were reduced from 80 +/- 6 to 58 +/- 8 mumol/g/hr by ethylhexanol. In contrast, ketone body production from hexanoate, which is activated in the mitochondria, was not affected by ethylhexanol. Basal and oleate-stimulated rates of H2O2 production were not affected by ethylhexanol, indicating that peroxisomal beta-oxidation was not altered by the compound. Based on these data it is concluded that 2-ethylhexanol inhibits beta-oxidation of fatty acids in mitochondria but not in peroxisomes. Treatment of rats with ethylhexanol (0.32 g/kg, i.p.) decreased plasma ketone bodies from 1.6 to 0.8 mM, increased hepatic triglycerides and increased lipid predominantly in periportal regions of the liver lobule. These data indicate that alterations in hepatic fatty acid metabolism in periportal regions of the liver lobule may be early events in peroxisome proliferation.

Animals↗

Lipid metabolism of the yellow clam, Mesodesma mactroides: 2-polyunsaturated fatty acid metabolism.

The fate of labeled linoleic, alpha-linolenic, and higher homologs of alpha-linolenic acid administered to the yellow clam, Mesodesma mactroides, was investigated. It was found that the clam incorporated the acids dissolved in sea water and converted 18:2 (n-6) into 20:2 (n-6) and 18:3 (n-3) into 18:4 (n-3) and 20:3 (n-3). The addition of casein hydrolysate to the sea water increased the desaturation capacity of the calm and allowed the conversion of 18:2 (n-6) into 18:3 (n-6) to be demonstrated. An enhanced desaturation of 18:3 (n-3) into 18:4 (n-3) was also demonstrated. After 12 hr admininistration of the acid, no radioactivity was found in arachidonic, 20:5 (n-3), or 22:6 (n-3). Feeding the clams a culture of Phaeodactylun tricornutum previously incubated with 1-14C-alph-linolenic acid demonstrated that all the homologs of the alpha-linolenic series were found in the clam without any important changes. Six hour administration of labled linolenic acid resulted in the incorporation of the acid into diglycerides and phospholipids.

Animals↗

Fatty acid metabolism in fasting elephant seal pups.

The turnover of two plasma free fatty acids (FFA) were measured in 5 northern elephant seal pups (Mirounga angustirostris) after approximately 2 months of post-weaning fasting. Turnover was determined using simultaneous bolus injections of 14C-palmitate, 3H-oleate and Evans blue (EB) administered via an indwelling extradural intravertebral catheter. At this time in their natural fast, the seals exhibited plasma FFA levels and turnover values higher than reported for other marine mammals and most terrestrial carnivores. There was no consistent difference between plasma FFA turnover measured by palmitate or oleate tracers. The results imply that FFA metabolism is the primary source of energy during fasting. This is interesting in light of previous observations of minimal ketoacid accumulation and low levels of glucose and protein energy production during fasting in these juvenile seals.

Animals↗

Influence of body fat distribution on free fatty acid metabolism in obesity.

UNLABELLED: In order to determine whether differences in body fat distribution result in specific abnormalities of free fatty acid (FFA) metabolism, palmitate turnover, a measure of systemic adipose tissue lipolysis, was measured in 10 women with upper body obesity, 9 women with lower body obesity, and 8 nonobese women under overnight postabsorptive (basal), epinephrine stimulated and insulin suppressed conditions. RESULTS: Upper body obese women had greater (P less than 0.005) basal palmitate turnover than lower body obese or nonobese women (2.8 +/- 0.2 vs. 2.1 +/- 0.2 vs. 1.8 +/- 0.2 mumol.kg lean body mass (LBM)-1.min-1, respectively), but a reduced (P less than 0.05) net lipolytic response to epinephrine (59 +/- 7 vs. 79 +/- 5 vs. 81 +/- 7 mumol palmitate/kg LBM, respectively). Both types of obesity were associated with impaired suppression of FFA turnover in response to euglycemic hyperinsulinemia compared to nonobese women (P less than 0.005). These specific differences in FFA metabolism may reflect adipocyte heterogeneity, which may in turn affect the metabolic aberrations associated with different types of obesity. These findings emphasize the need to characterize obese subjects before studies.

Adipose Tissue↗