Fatty Acid Oxidation, Citric Acid Cycle Activity, and Morphology of Mitochondria in Diabetic Rat Liver

1969 ◽  
Vol 131 (3) ◽  
pp. 913-917 ◽  
Author(s):  
Y. Harano ◽  
R. G. DePalma ◽  
M. Miller
Keyword(s):  
Fatty Acid ◽  
Citric Acid ◽  
Fatty Acid Oxidation ◽  
Rat Liver ◽  
Citric Acid Cycle ◽  
Diabetic Rat ◽  
Acid Oxidation ◽  
Acid Cycle

scholarly journals Citrus Flavanones Affect Hepatic Fatty Acid Oxidation in Rats by Acting as Prooxidant Agents

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Rodrigo Polimeni Constantin ◽  
Gilson Soares do Nascimento ◽  
Renato Polimeni Constantin ◽  
Clairce Luzia Salgueiro ◽  
Adelar Bracht ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Citric Acid ◽  
Oxygen Uptake ◽  
Fatty Acid Oxidation ◽  
Citric Acid Cycle ◽  
Acid Oxidation ◽  
Acid Cycle ◽  
Hepatic Fatty Acid ◽  
Wide Range ◽  
Hepatic Fatty Acid Oxidation

Citrus flavonoids have a wide range of biological activities and positive health effects on mammalian cells because of their antioxidant properties. However, they also act as prooxidants and thus may interfere with metabolic pathways. The purpose of this work was to evaluate the effects of three citrus flavanones, hesperidin, hesperetin, and naringenin, on several parameters linked to fatty acid oxidation in mitochondria, peroxisomes, and perfused livers of rats. When exogenous octanoate was used as substrate, hesperetin and naringenin reduced the mitochondrial NADH/NAD+ratio and stimulated the citric acid cycle without significant changes on oxygen uptake or ketogenesis. When fatty acid oxidation from endogenous sources was evaluated, hesperetin and naringenin strongly reduced the mitochondrial NADH/NAD+ratio. They also inhibited both oxygen uptake and ketogenesis and stimulated the citric acid cycle. Hesperidin, on the other hand, had little to no effect on these parameters. These results confirm the hypothesis that citrus flavanones are able to induce a more oxidised state in liver cells, altering parameters related to hepatic fatty acid oxidation. The prooxidant effect is most likely a consequence of the ability of these substances to oxidise NADH upon production of phenoxyl radicals in the presence of peroxidases and hydrogen peroxide.

scholarly journals Lipotoxic Palmitate Impairs the Rate of β-Oxidation and Citric Acid Cycle Flux in Rat Neonatal Cardiomyocytes

2016 ◽  
Vol 40 (5) ◽  
pp. 969-981 ◽  
Author(s):  
Taha Haffar ◽  
Ali Akoumi ◽  
Nicolas Bousette
Keyword(s):  
Fatty Acid ◽  
Citric Acid ◽  
Dehydrogenase Activity ◽  
Fatty Acid Oxidation ◽  
Isocitrate Dehydrogenase ◽  
Lipid Accumulation ◽  
Citric Acid Cycle ◽  
Acid Oxidation ◽  
Acid Cycle ◽  
Neonatal Cardiomyocytes

Background/Aims: Diabetic hearts exhibit intracellular lipid accumulation. This suggests that the degree of fatty acid oxidation (FAO) in these hearts is insufficient to handle the elevated lipid uptake. We previously showed that palmitate impaired the rate of FAO in primary rat neonatal cardiomyocytes. Here we were interested in characterizing the site of FAO impairment induced by palmitate since it may shed light on the metabolic dysfunction that leads to lipid accumulation in diabetic hearts. Methods: We measured fatty acid oxidation, acetyl-CoA oxidation, and carnitine palmitoyl transferase (Cpt1b) activity. We measured both forward and reverse aconitase activity, as well as NAD+ dependent isocitrate dehydrogenase activity. We also measured reactive oxygen species using the 2', 7'-Dichlorofluorescin Diacetate (DCFDA) assay. Finally we used thin layer chromatography to assess diacylglycerol (DAG) levels. Results: We found that palmitate significantly impaired mitochondrial β-oxidation as well as citric acid cycle flux, but not Cpt1b activity. Palmitate negatively affected net aconitase activity and isocitrate dehydrogenase activity. The impaired enzyme activities were not due to oxidative stress but may be due to DAG mediated PKC activation. Conclusion: This work demonstrates that palmitate, a highly abundant fatty acid in human diets, causes impaired β-oxidation and citric acid cycle flux in primary neonatal cardiomyocytes. This metabolic defect occurs prior to cell death suggesting that it is a cause, rather than a consequence of palmitate mediated lipotoxicity. This impaired mitochondrial metabolism can have important implications for metabolic diseases such as diabetes and obesity.

The Role of Lipid in Adult Development and Flight-Muscle Metabolism in Hyalophora Cecropia

1964 ◽  
Vol 41 (3) ◽  
pp. 573-590
Author(s):  
LAWRENCE A. DOMROESE ◽  
LAWRENCE I. GILBERT
Keyword(s):  
Fatty Acid ◽  
Citric Acid ◽  
Fatty Acid Oxidation ◽  
Adult Development ◽  
Citric Acid Cycle ◽  
Flight Muscle ◽  
Muscle Metabolism ◽  
Metabolic Inhibitors ◽  
Acid Oxidation ◽  
Acid Cycle

1. Changes in total lipid and R.Q. show that female pupae of H. cecropia begin to catabolize lipid early in adult development. In males there is a conservation of lipid during adult development resulting in the male moth having about three times the lipid content of the female. In the adult moth both sexes utilize lipid as the major energy source. 2. Lipid is the available substrate as well as the preferred substrate in flight-muscle metabolism in male moths. 3. Flight-muscle homogenates show greater oxidative activity with fatty acids and citric acid cycle intermediates than with glucose or glycolytic intermediates, indicating that carbohydrate pathways are not prominent. 4. A fatty acid oxidizing system has been identified in flight muscle which requires ATP, magnesium and a citric acid cycle intermediate for optimum activity. 5. Experiments with radiotracers and metabolic inhibitors reveal that fatty acid oxidation in flight muscle proceeds via the citric acid cycle and the cytochrome chain. 6. Active fatty acid activating enzymes are present in flight muscle, and fatty acid oxidation in H. cecropia is discussed in relation to vertebrate and other invertebrate systems.

scholarly journals Effects of pent-4-enoate on cellular redox state, glycolysis and fatty acid oxidation in isolated perfused rat heart

1978 ◽  
Vol 170 (2) ◽  
pp. 235-240 ◽  
Author(s):  
J. Kalervo Hiltunen ◽  
V. Pekka Jauhonen ◽  
Markku J. Savolainen ◽  
Ilmo E. Hassinen
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Citric Acid ◽  
Redox State ◽  
Citric Acid Cycle ◽  
Beating Heart ◽  
Acid Oxidation ◽  
O2 Consumption ◽  
Cellular Redox ◽  
Acid Cycle

The metabolic effects of pent-4-enoate were studied in beating and potassium-arrested perfused rat hearts. The addition of 0.8mm-pent-4-enoate to the fluid used to perfuse a potassium-arrested heart resulted in a 70% increase in the O2 consumption and a 66% decrease in the glycolytic flux as measured in terms of the de-tritiation of [3-3H]glucose, although the proportion of the O2 consumption attributable to glucose oxidation decreased from an initial 30% to 10%. The pent-4-enoate-induced increase in O2 consumption was only 15% in the beating heart. In the potassium-arrested heart, pent-4-enoate stimulated palmitate oxidation by more than 100% when measured in terms of the production of 14CO2 from [1-14C]palmitate, but in the beating heart palmitate oxidation was inhibited. Perfusion of the heart with pent-4-enoate had no effect on the proportion of pyruvate dehydrogenase found in the active form, in spite of large changes in the CoASH and acetyl-CoA concentrations and changes in their concentration ratios. The effects of pent-4-enoate on the cellular redox state were dependent on the ATP consumption of the heart. In the beating heart, pent-4-enoate caused a rapid mitochondrial NAD+ reduction that subsequently faded out, so that the final state was more oxidized than the initial state. The arrested heart, however, remained in a more reduced state than initially, even after the partial re-oxidation that followed the initial rapid NAD+ reduction. The ability of pent-4-enoate to increase or decrease fatty acid oxidation can be explained on the basis of the differential effects of pent-4-enoate on the concentration of citric acid-cycle intermediates under conditions of high or low ATP consumption of the myocardial cell. The proportion of the fatty acids in the fuel consumed by the heart is probably primarily determined by the regulatory mechanisms of glycolysis. When pent-4-enoate causes an increase in the citric acid-cycle intermediates, feedback inhibition of glycolysis results in an increase in the oxidation of fatty acids.

An explanation for decreased ketogenesis in the liver of the obese Zucker rat

1989 ◽  
Vol 257 (4) ◽  
pp. R822-R828 ◽  
Author(s):  
M. J. Azain ◽  
J. A. Ontko
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Rat Liver ◽  
Intact Cell ◽  
Zucker Rats ◽  
Acid Oxidation ◽  
Palmitate Oxidation ◽  
Malonyl Coa ◽  
Obese Zucker Rats ◽  
Rat Livers

These studies were undertaken to further characterize and explain the differences in hepatic fatty acid metabolism between lean and obese Zucker rats. It was shown that the rate of palmitate or octanoate oxidation and the inhibition of palmitate oxidation by malonyl CoA in mitochondria isolated from lean and obese Zucker rats were similar. Cytochrome oxidase activity was similar in lean and obese rat livers. It was found that the addition of cytosol from the obese rat liver inhibited palmitate oxidation by 20-30% in mitochondria isolated from lean or obese rat livers and thus reproduced the conditions observed in the intact cell. Increased concentrations of metabolites such as malonyl CoA and glycerophosphate in the liver of the obese rat are likely contributors to this inhibitory effect. These results are extrapolated to the intact cell and suggest that decreased hepatic fatty acid oxidation in the obese rat can be accounted for by cytosolic influences on the mitochondria. The decreased rate of fatty acid oxidation observed in the intact hepatocyte or perfused liver cannot be explained by a defect in the capacity of mitochondria to oxidize substrate or by a decrease in mitochondrial number in the obese rat liver.

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