scholarly journals Microcytophotometric analysis of human osteoclast metabolism: lack of activity in certain oxidative pathways indicates inability to sustain biosynthesis during resorption.

1994 ◽  
Vol 42 (5) ◽  
pp. 599-606 ◽  
Author(s):  
R A Dodds ◽  
M Gowen ◽  
J N Bradbeer
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
De Novo ◽  
Krebs Cycle ◽  
Maximal Activity ◽  
Good Evidence ◽  
Acid Oxidation ◽  
Atp Production ◽  
Metabolic Characteristics

It has been proposed that highly biosynthetic cells oxidize fatty acids to generate ATP while maintaining high levels of glucose metabolism through the glycolytic and pentose shunt systems to supply biosynthetic intermediates. We investigated the metabolic strategies and substrate for ATP production in the osteoclast. We used in situ quantitative microcytophotometric techniques to determine the maximal activity of the pentose shunt (glucose-6-phosphate dehydrogenase; G6PD), the glycolytic pathway (glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase; G3PD and LDH), fatty acid oxidation (beta-hydroxyacyl dehydrogenase; HOAD), and the Krebs cycle (succinate dehydrogenase; SDH) in human osteoclasts in situ, and related these enzyme activities to the degree of involvement of the cells in resorption. Unlike other highly biosynthetic cells, such as chondrocytes and macrophage polykaryons, osteoclasts associated with bone resorption were deficient in G3PD, LDH, and G6PD activity. However, osteoclasts did demonstrate a capacity for fatty acid oxidation which increased in cells apposed to the bone surface. The lack of significant glycolytic and pentose shunt activity in the osteoclast provides good evidence that resorbing osteoclasts, unlike phagocytosing macrophage polykaryons, have the metabolic characteristics of cells with greatly reduced capabilities of de novo mRNA synthesis but which do maintain high rates of ATP production. The possibility that the loss of glycolytic activity is a prelude to cell death is discussed.

scholarly journals EFFECTS OF CORTISOL ON CULTURED RAT HEART CELLS

1973 ◽  
Vol 57 (1) ◽  
pp. 109-116 ◽  
Author(s):  
J. V. Anastasia ◽  
R. L. McCarl
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Fatty Acid Oxidation ◽  
Growth Medium ◽  
Rat Heart ◽  
Acid Oxidation ◽  
Heart Cells ◽  
Atp Production ◽  
Rat Heart Cells

This paper reports the determination of the ability of rat heart cells in culture to release [14C]palmitate from its triglyceride and to oxidize this fatty acid and free [14C]palmitate to 14CO2 when the cells are actively beating and when they stop beating after aging in culture. In addition, the levels of glucose, glycogen, and ATP were determined to relate the concentration of these metabolites with beating and with cessation of beating. When young rat heart cells in culture are actively beating, they oxidize free fatty acids at a rate parallel with cellular ATP production. Both fatty acid oxidation and ATP production remain constant while the cells continue to beat. Furthermore, glucose is removed from the growth medium by the cells and stored as glycogen. When cultured cells stop beating, a decrease is seen in their ability to oxidize free fatty acids and to release them from their corresponding triglycerides. Concomitant with decreased fatty acid oxidation is a decrease in cellular levels of ATP until beating ceases. Midway between initiation of cultures and cessation of beating the cells begin to mobilize the stored glycogen. When the growth medium is supplemented with cortisol acetate and given to cultures which have ceased to beat, reinitiation of beating occurs. Furthermore, all decreases previously observed in ATP levels, fatty acid oxidation, and esterase activity are restored.

scholarly journals Nrf2 affects the efficiency of mitochondrial fatty acid oxidation

2014 ◽  
Vol 457 (3) ◽  
pp. 415-424 ◽  
Author(s):  
Marthe H. R. Ludtmann ◽  
Plamena R. Angelova ◽  
Ying Zhang ◽  
Andrey Y. Abramov ◽  
Albena T. Dinkova-Kostova
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Saturated Fatty Acids ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Atp Production ◽  
Mitochondrial Fatty Acid ◽  
Mitochondrial Oxidation ◽  
Long Chain

Transcription factor Nrf2 affects fatty acid oxidation; the mitochondrial oxidation of long-chain (palmitic) and short-chain (hexanoic) saturated fatty acids is depressed in the absence of Nrf2 and accelerated when Nrf2 is constitutively activated, affecting ATP production and FADH2 utilization.

Glucose and Fatty Acid Oxidation by the In Situ Dog Heart During Experimental Cooling and Rewarming

1998 ◽  
Vol 65 (5) ◽  
pp. 1235-1240 ◽  
Author(s):  
Terje K. Steigen ◽  
Torkjel Tveita ◽  
Olav Hevrøy ◽  
Thomas V. Andreasen ◽  
Terje S. Larsen
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Dog Heart

Epinephrine increases ATP production in hearts by preferentially increasing glucose metabolism

1994 ◽  
Vol 267 (5) ◽  
pp. H1862-H1871 ◽  
Author(s):  
R. L. Collins-Nakai ◽  
D. Noseworthy ◽  
G. D. Lopaschuk
Keyword(s):  
Fatty Acid ◽  
Glucose Metabolism ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Contractile Function ◽  
Pyruvate Dehydrogenase Complex ◽  
Active Form ◽  
Acid Oxidation ◽  
Complex Activity ◽  
Atp Production

Although epinephrine is widely used clinically, its effect on myocardial energy substrate preference in the intact heart has yet to be clearly defined. We determined the effects of epinephrine on glucose and fatty acid metabolism in isolated working rat hearts perfused with 11 mM glucose, 0.4 mM palmitate, and 100 muU/ml insulin at an 11.5-mmHg left atrial preload and a 60-mmHg aortic afterload. Glycolysis and glucose oxidation were measured in hearts perfused with [5–3H]glucose and [U-14C]glucose, whereas fatty acid oxidation was measured in hearts perfused with [1–14C]palmitate. Addition of 1 microM epinephrine resulted in a 53% increase in the heart rate-developed pressure product. Glycolysis increased dramatically following addition of epinephrine (a 272% increase), as did glucose oxidation (a 410% increase). In contrast, fatty acid oxidation increased by only 10%. Epinephrine treatment did not increase the amount of oxygen required to produce an equivalent amount of ATP; however, epinephrine did increase the uncoupling between glycolysis and glucose oxidation in these fatty acid-perfused hearts, resulting in a significant increase in H+ production from glucose metabolism. Overall ATP production in epinephrine-treated hearts increased 59%. The contribution of glucose (glycolysis and glucose oxidation) to ATP production increased from 13 to 36%, which was accompanied by a reciprocal decrease in the contribution of fatty acid oxidation to ATP production from 83 to 63%. The increase in glucose oxidation was accompanied by a significant increase in pyruvate dehydrogenase complex activity in the active form. We conclude that the increase in ATP required for contractile function following epinephrine treatment occurs through a preferential increase in glucose use.

Abstract 17036: Cardiomyocyte Krüppel-Like Factor 5 Regulates Ceramide Biosynthesis and Promotes Systolic Dysfunction in Ischemic Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Matthew K Hoffman ◽  
Ioannis Kyriazis ◽  
Dimitra Palioura ◽  
Maria Cimini ◽  
Sudarsan Rajan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
De Novo ◽  
Systolic Dysfunction ◽  
Ischemic Heart ◽  
Acid Oxidation ◽  
Ischemic Heart Failure ◽  
Specific Expression ◽  
Protein Levels

Introduction: Our lab previously showed that cardiomyocyte Krüppel-like factor (KLF)-5 regulates cardiac fatty acid oxidation. Various studies have associated heart failure with altered cardiac fatty acid oxidation and lipotoxicity. Hypothesis: Aberrant regulation of KLF5 contributes to pathophysiology and metabolic perturbations in ischemic heart failure. Methods and Results: Analysis of KLF5 mRNA and protein levels in human ischemic heart failure samples and in rodent models 2- and 4-weeks post-myocardial infarction (MI) showed significantly increased KLF5 expression. To investigate the involvement of KLF5 in the pathophysiology of ischemic heart failure, we treated mice that were subjected to MI with a pharmacological KLF5 inhibitor (ML264). ML264 increased ejection fraction and reduced diastolic volume. Likewise, mice with cardiomyocyte-specific KLF5 deletion (αMHC-KLF5 -/- mice) were protected from ischemic heart failure. Lipidomic analysis by LC-MS/MS showed that αMHC-KLF5 -/- mice after MI had lower myocardial ceramide levels compared with control mice with MI. Accordingly, the expression of cardiac SPTLC1 and SPTLC2, which regulate de novo ceramide biosynthesis, was higher in control mice with MI and lower in αMHC-KLF5 -/- mice with MI. KLF5 overexpression in HL1 cardiomyocytes increased SPTLC1 and SPTLC2 mRNA and protein levels. ChIP-qPCR and luciferase promoter assays showed that KLF5 activates the promoters of these genes via direct binding. To assess the transcriptional effects of KLF5 independent from other changes that occur with MI, we generated a mouse model of inducible (Dox-ON), cardiomyocyte-specific expression of KLF5 (αMHC-rtTA-KLF5). Systolic dysfunction was evident 2-weeks following KLF5 induction. Heart tissue from these mice exhibited increased SPTLC1 and SPTLC2 mRNA and protein levels, and inhibition of SPT using myriocin suppressed myocardial ceramide levels and alleviated systolic dysfunction. Conclusions: KLF5 is induced during the development of ischemic heart failure in humans and mice, and stimulates expression of SPTLC1 and SPTLC2 that promote ceramide biosynthesis. KLF5 inhibition emerges as a novel therapeutic target to protect against ischemic heart failure.

Triacylglycerol turnover in isolated working hearts of acutely diabetic rats

1994 ◽  
Vol 72 (10) ◽  
pp. 1110-1119 ◽  
Author(s):  
Maruf Saddik ◽  
Gary D. Lopaschuk
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Acid Oxidation ◽  
Atp Production ◽  
Oxidation Rates ◽  
Rat Hearts

Although myocardial triacylglycerol may be a potentially important source of fatty acids for β-oxidation in diabetes, few studies have measured triacylglycerol turnover directly in hearts from diabetic animals. In this study, myocardial triacylglycerol turnover was directly measured in isolated working hearts from streptozotocin-induced acutely diabetic rats. Hearts were initially perfused in the presence of 1.2 mM [14C]palmitate and 11 mM glucose for 1 h (pulse) to label the endogenous lipid pools, followed by a 10-min washout perfusion. Hearts were then perfused for another hour (chase) with buffer containing 11 mM glucose ± 1.2 mM [3H]palmitate. During the chase, both 14CO2 and 3H2O production (measures of endogenous and exogenous fatty acid oxidation, respectively) were determined. A second series of hearts were perfused using the same protocol, except that unlabeled palmitate was used during the pulse and 11 mM [14C(U),5-3H]glucose ± unlabeled palmitate was present during the chase. Both glycolysis (3H2O production) and glucose oxidation (14CO2 production) rates were measured in this series. Myocardial triacylglycerol levels were significantly higher in the diabetic rat hearts (77.5 ± 4.6 vs. 33.7 ± 4.1 μmol fatty acid/g dry mass in control hearts). In diabetic rat hearts chased with 1.2 mM palmitate, triacylglycerol lipolysis was increased, although endogenous [14C]palmitate oxidation rates were similar to control hearts and contributed 10.1% of overall ATP production. The majority of fatty acids derived from triacylglycerol lipolysis were released into the perfusate. In the absence of palmitate, both triacylglycerol lipolysis and endogenous [14C]palmitate oxidation rates were significantly increased in diabetic rat hearts, compared with control. Under these conditions, triacylglycerol fatty acid oxidation contributed 70% of steady-state ATP production in diabetic rat hearts, compared with 34% in control hearts. These results demonstrate that in diabetic rat hearts myocardial triacylglycerol lipolysis is significantly increased and can readily be used as a source of fatty acids for mitochondrial β-oxidation.Key words: heart, triacylglycerols, fatty acid oxidation, glucose oxidation, glycolysis.

scholarly journals Alteration of Energy Substrates and ROS Production in Diabetic Cardiomyopathy

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
O. Lorenzo ◽  
E. Ramírez ◽  
B. Picatoste ◽  
J. Egido ◽  
J. Tuñón
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Diabetic Cardiomyopathy ◽  
Receptor Interaction ◽  
Acid Oxidation ◽  
Mitochondrial Uncoupling ◽  
Energy Substrates ◽  
Atp Production ◽  
Fatty Acid Derivatives ◽  
Or Gene

Diabetic cardiomyopathy is initiated by alterations in energy substrates. Despite excess of plasma glucose and lipids, the diabetic heart almost exclusively depends on fatty acid degradation. Glycolytic enzymes and transporters are impaired by fatty acid metabolism, leading to accumulation of glucose derivatives. However, fatty acid oxidation yields lower ATP production per mole of oxygen than glucose, causing mitochondrial uncoupling and decreased energy efficiency. In addition, the oxidation of fatty acids can saturate and cause their deposition in the cytosol, where they deviate to induce toxic metabolites or gene expression by nuclear-receptor interaction. Hyperglycemia, the fatty acid oxidation pathway, and the cytosolic storage of fatty acid and glucose/fatty acid derivatives are major inducers of reactive oxygen species. However, the presence of these species can be essential for physiological responses in the diabetic myocardium.

scholarly journals Vitamin B12 Induces Hepatic Fatty Infiltration through Altered Fatty Acid Metabolism

2021 ◽  
Vol 55 (3) ◽  
pp. 241-255
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Vitamin B12 ◽  
Fatty Acid Oxidation ◽  
Lipid Droplets ◽  
De Novo ◽  
Quantitative Polymerase Chain Reaction ◽  
Saturated Fatty Acids ◽  
Fatty Infiltration ◽  
Acid Oxidation

Background/Aims: Rise in global incidence of obesity impacts metabolic health. Evidence from human and animal models show association of vitamin B12 (B12) deficiency with elevated BMI and lipids. Human adipocytes demonstrated dysregulation of lipogenesis by low B12 via hypomethylation and altered microRNAs. It is known de novo hepatic lipogenesis plays a key role towards dyslipidaemia, however, whether low B12 affects hepatic metabolism of lipids is not explored. Methods: HepG2 was cultured in B12-deficient EMEM medium and seeded in different B12 media: 500nM(control), 1000pM(1nM), 100pM and 25pM(low) B12. Lipid droplets were examined by Oil Red O (ORO) staining using microscopy and then quantified by elution assay. Gene expression were assessed with real-time quantitative polymerase chain reaction (qRT-PCR) and intracellular triglycerides were quantified using commercial kit (Abcam, UK) and radiochemical assay. Fatty acid composition was measured by gas chromatography and mitochondrial function by seahorse XF24 flux assay. Results: HepG2 cells in low B12 had more lipid droplets that were intensely stained with ORO compared with control. The total intracellular triglyceride and incorporation of radio-labelled-fatty acid in triglyceride synthesis were increased. Expression of genes regulating fatty acid, triglyceride and cholesterol biosynthesis were upregulated. Absolute concentrations of total fatty acids, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), trans-fatty acids and individual even-chain and odd-chain fatty acids were significantly increased. Also, low B12 impaired fatty acid oxidation and mitochondrial functional integrity in HepG2 compared with control. Conclusion: Our data provide novel evidence that low B12 increases fatty acid synthesis and levels of individual fatty acids, and decreases fatty acid oxidation and mitochondrial respiration, thus resulting in dysregulation of lipid metabolism in HepG2. This highlights the potential significance of de novo lipogenesis and warrants possible epigenetic mechanisms of low B12.

Abstract 328: Med13 regulates cardiac metabolism

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Kedryn K Baskin ◽  
Chad E Grueter ◽  
Christine M Kusminski ◽  
Philipp E Scherer ◽  
Rhonda Bassel-Duby ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Fatty Acid ◽  
Glucose Uptake ◽  
Fatty Acid Oxidation ◽  
Electron Flow ◽  
Krebs Cycle ◽  
Cardiac Metabolism ◽  
Acid Oxidation ◽  
Intermediary Metabolites ◽  
Consumption Rates

Background: The heart is a metabolic organ that primarily utilizes fatty acids as energy substrate. While it is well established that the heart is metabolically flexible, the transcriptional network regulating cardiac metabolism is only partially understood. We have previously demonstrated that cardiac overexpression of Med13, a component of the Mediator Complex that regulates transcription, results in a lean phenotype with enhanced basal metabolic rates. We now investigate the mechanisms contributing to metabolic changes in mice with cardiac over-expression of Med13(Med13cTg). Methods and Results: Cardiac fludeoxyglucose (18F-FDG)-PET imaging analysis revealed that Med13cTg hearts take up more glucose than wild type littermates. To determine pathways responsible for enhanced glucose uptake, ventricles from Med13cTg mice were subjected to RNA-seq and metabolomic analysis. The expression of fatty acid oxidation genes was decreased in Med13cTg hearts, accompanied by an increase in acyl CoA and a decrease in acetyl CoA. These data suggest that beta oxidation is decreased in Med13cTg hearts. Mitochondria function was therefore determined in Med13cTg hearts by performing electron-flow analyses and assessing oxygen consumption rates. Indeed, oxygen consumption rates were decreased in mitochondria isolated from Med13cTg hearts. Expression of Krebs Cycle genes and corresponding intermediary metabolites were also decreased in Med13cTg hearts, suggesting decreased flux through this pathway as well. Conclusions: Overexpression of Med13 in the heart increases glucose uptake and decreases fatty acid oxidation in the heart. We speculate that Med13 transcriptionally regulates key mediators of cardiac metabolism. The mechanisms by which this occurs are currently under investigation.

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