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.

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.

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.

scholarly journals Isocitrate Dehydrogenase of Bradyrhizobium japonicum Is Not Required for Symbiotic Nitrogen Fixation with Soybean

2006 ◽  
Vol 188 (21) ◽  
pp. 7600-7608 ◽  
Author(s):  
Ritu Shah ◽  
David W. Emerich
Keyword(s):  
Nitrogen Fixation ◽  
Citric Acid ◽  
Dehydrogenase Activity ◽  
Mutant Strain ◽  
Isocitrate Dehydrogenase ◽  
Bradyrhizobium Japonicum ◽  
Citric Acid Cycle ◽  
Symbiotic Nitrogen Fixation ◽  
Nodule Development ◽  
Acid Cycle

ABSTRACT A mutant strain of Bradyrhizobium japonicum USDA110 lacking isocitrate dehydrogenase activity was created to determine whether this enzyme was required for symbiotic nitrogen fixation with soybean (Glycine max cv. Williams 82). The isocitrate dehydrogenase mutant, strain 5051, was constructed by insertion of a streptomycin resistance gene cassette. The mutant was devoid of isocitrate dehydrogenase activity and of immunologically detectable protein, indicating there is only one copy in the genome. Strain 5051 grew well on a variety of carbon sources, including arabinose, pyruvate, succinate, and malate, but, unlike many microorganisms, was a glutamate auxotroph. Although the formation of nodules was slightly delayed, the mutant was able to form nodules on soybean and reduce atmospheric dinitrogen as well as the wild type, indicating that the plant was able to supply sufficient glutamate to permit infection. Combined with the results of other citric acid cycle mutants, these results suggest a role for the citric acid cycle in the infection and colonization stage of nodule development but not in the actual fixation of atmospheric dinitrogen.

scholarly journals 2-Mercaptoacetate administration depresses the β-oxidation pathway through an inhibition of long-chain acyl-CoA dehydrogenase activity

1981 ◽  
Vol 196 (3) ◽  
pp. 803-809 ◽  
Author(s):  
F Bauché ◽  
D Sabourault ◽  
Y Giudicelli ◽  
J Nordmann ◽  
R Nordmann
Keyword(s):  
Fatty Acid ◽  
Dehydrogenase Activity ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Beta Oxidation ◽  
Oxidation Pathway ◽  
Respiration Rates ◽  
Chain Acyl ◽  
The One ◽  
Mitochondrial Defect

To elucidate the mechanisms through which 2-mercaptoacetate administration inhibits fatty acid oxidation in the liver, the respiration rates induced by different substrates were studied polarographically in rat hepatic mitochondria isolated 3 h after 2-mercaptoacetate administration. Palmitoyl-L-carnitine oxidation was almost completely inhibited in either the absence or presence of malonate. Octanoate oxidation was also inhibited, and the intramitochondrial acyl-CoA content was markedly increased. The oxidation rate of pyruvate and 2-oxoglutarate on the one hand and of 3-hydroxybutyrate, succinate and glutamate on the other was either normal or only slightly decreased. In the presence of 2,4-dinitrophenol, the extent of the inhibition of palmitoyl-L-carnitine oxidation was unchanged. All these results are consistent with the hypothesis that the 2-mercaptoacetate inhibition of fatty acid oxidation is due to an inhibition of the beta-oxidation pathway itself. Finally, the mitochondrial defect responsible for this inhibition was shown to be an inhibition of palmitoyl-CoA dehydrogenase activity (EC 1.3.99.3).

scholarly journals MON-672 Progesterone Receptor Membrane Component 1 Suppresses Lipid Accumulation and Lipotoxicity in Animal Model of Diabetic Cardiomyopathy (DCM)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sang R Lee ◽  
Eui-ju Hong
Keyword(s):  
Fatty Acid ◽  
Progesterone Receptor ◽  
Fatty Acid Oxidation ◽  
Diabetic Cardiomyopathy ◽  
Mitochondrial Respiration ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Acid Oxidation ◽  
High Fat ◽  
Membrane Component

Abstract Diabetic cardiomyopathy (DCM) is one of the complications triggered by type II diabetes (T2D) (1). When free fatty acids (FFA) are abundant in insulin resistant pre-diabetic patients because of adipose lipolysis, FFA tends to move toward heart (2). Lipid accumulation can cause cardiac lipotoxicity and exacerbate DCM (3). In previous study, Pgrmc1 has been identified to associate with fatty acid synthesis (4). Therefore, we assumed that Pgrmc1 will associate with DCM. By feeding high-fat diet for 8 weeks and injecting streptozotocin (30mg/kg), T2D and DCM were induced. The lipid accumulation was exacerbated in T2D-induced Pgrmc1 KO heart, and FFA level was also high. Levels of lipid metabolic genes showed the tendency for lipid accumulation and lipotoxicity, and glycolysis was induced in T2D-induced Pgrmc1 KO heart. Though glycolysis presents higher efficiency for energy production in cardiomyopathy (5), it did not compensate the impairment of mitochondrial respiration in Pgrmc1 KO heart. High-fat diet and streptozotocin could not be the interfering factors, because suppression of fatty acid oxidation, induction of glycolysis, and impairment of mitochondrial respiration were observed similarly in post-prandial mice which were fed with normal chow. Insulin was excluded for interfering factor as cell line with serum starvation showed mitochondrial suppression and glycolytic induction in flux analyzer analysis in Pgrmc1 knockdown. Conversely, induction of fatty acid oxidation and suppression of glycolysis were observed in 72 h fasting of Pgrmc1 KO heart, suggesting the nutrition is closely associated with the metabolic modulation of Pgrmc1 on heart. This metabolic phenotype of Pgrmc1 KO heart consequently exacerbated DCM by showing high levels of fibrosis, inflammation, endoplasmic reticulum stress, and oxidative stress. References: (1) Jia G, Hill MA, Sowers JR. Diabetic Cardiomyopathy: An Update of Mechanisms Contributing to This Clinical Entity. Circulation research. 2018;122:624-38. (2) Noll C, Carpentier AC. Dietary fatty acid metabolism in prediabetes. Current opinion in lipidology. 2017;28:1-10. (3) Goldberg IJ, Trent CM, Schulze PC. Lipid metabolism and toxicity in the heart. Cell metabolism. 2012;15:805-12. (4) Lee SR, Kwon SW, Kaya P, Lee YH, Lee JG, Kim G, et al. Loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis. Scientific reports. 2018;8:15711. (5) Nagoshi T, Yoshimura M, Rosano GM, Lopaschuk GD, Mochizuki S. Optimization of cardiac metabolism in heart failure. Current pharmaceutical design. 2011;17:3846-53.

scholarly journals Detection of myocardial medium‐chain fatty acid oxidation and tricarboxylic acid cycle activity with hyperpolarized [1– 13 C]octanoate

2020 ◽  
Vol 33 (3) ◽  
Author(s):  
Hikari A.I. Yoshihara ◽  
Jessica A.M. Bastiaansen ◽  
Magnus Karlsson ◽  
Mathilde H. Lerche ◽  
Arnaud Comment ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Chain Fatty Acid ◽  
Medium Chain Fatty Acid ◽  
Acid Oxidation ◽  
Acid Cycle ◽  
Medium Chain
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