Increased glucose oxidation in H-FABP null soleus muscle is associated with defective triacylglycerol accumulation and mobilization, but not with the defect of exogenous fatty acid oxidation

2006 ◽  
Vol 296 (1-2) ◽  
pp. 59-67 ◽  
Author(s):  
Sean Adhikari ◽  
Erdal Erol ◽  
Bert Binas
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Soleus Muscle ◽  
Glucose Oxidation ◽  
Acid Oxidation ◽  
Exogenous Fatty Acid ◽  
Triacylglycerol Accumulation

Abstract 12117: The Cardioprotection of Trimetazidine Against Ischemic Injury is Mediated by AMPK and ERK Signaling Pathway

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Zhenling Liu ◽  
Yina Ma ◽  
Michelle Kuznicki ◽  
Xingchi Chen ◽  
Wanqing Sun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Ex Vivo ◽  
Ischemic Injury ◽  
Erk Signaling ◽  
Acid Oxidation ◽  
Ampk Signaling ◽  
Heart Perfusion

Introduction: Trimetazidine (TMZ) is an anti-anginal drug that has been widely used in Europe and Asia. The TMZ can optimize energy metabolism via inhibition of long-chain 3-ketoacyl CoA thiolase (3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. However, the mechanism by which TMZ aids in cardioprotection against ischemic injury has not been characterized. Hypothesis: AMP-activated protein kinase (AMPK) is an energy sensor that control ATP supply from substrate metabolism and protect heart from energy stress. TMZ changes the cardiac AMP/ATP ratio via modulating fatty acid oxidation, thereby it may trigger AMPK signaling cascade that contribute to protection heart from ischemia/reperfusion (I/R) injury. Methods: The mouse in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery (LAD) were used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead (KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. Results: TMZ treatment significantly stimulates cardiac AMPK and extracellular signal-regulated kinase (ERK) signaling pathways (p<0.05 vs. vehicle group). The administration of TMZ reduces myocardial infarction size in WT C57BL/6J hearts, the reduction of myocardial infarction size by TMZ in AMPK KD hearts was significantly impaired versus WT hearts (p<0.05). Intriguingly, the administration of ERK inhibitor, PD 98059, to AMPK KD mice abolished the cardioprotection of TMZ against I/R injury. The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Conclusions: Both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. The metabolic benefits of TMZ for angina patients could be due to the activation of energy sensor AMPK in the heart by TMZ administration.

scholarly journals Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart

2016 ◽  
Vol 311 (2) ◽  
pp. H347-H363 ◽  
Author(s):  
Arata Fukushima ◽  
Osama Abo Alrob ◽  
Liyan Zhang ◽  
Cory S. Wagg ◽  
Tariq Altamimi ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Energy Metabolism ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Acid Oxidation ◽  
Amino Acid Synthesis ◽  
Oxidation Rates ◽  
Cardiac Energy Metabolism ◽  
Cardiac Energy ◽  
The Impact

Dramatic maturational changes in cardiac energy metabolism occur in the newborn period, with a shift from glycolysis to fatty acid oxidation. Acetylation and succinylation of lysyl residues are novel posttranslational modifications involved in the control of cardiac energy metabolism. We investigated the impact of changes in protein acetylation/succinylation on the maturational changes in energy metabolism of 1-, 7-, and 21-day-old rabbit hearts. Cardiac fatty acid β-oxidation rates increased in 21-day vs. 1- and 7-day-old hearts, whereas glycolysis and glucose oxidation rates decreased in 21-day-old hearts. The fatty acid oxidation enzymes, long-chain acyl-CoA dehydrogenase (LCAD) and β-hydroxyacyl-CoA dehydrogenase (β-HAD), were hyperacetylated with maturation, positively correlated with their activities and fatty acid β-oxidation rates. This alteration was associated with increased expression of the mitochondrial acetyltransferase, general control of amino acid synthesis 5 like 1 (GCN5L1), since silencing GCN5L1 mRNA in H9c2 cells significantly reduced acetylation and activity of LCAD and β-HAD. An increase in mitochondrial ATP production rates with maturation was associated with the decreased acetylation of peroxisome proliferator-activated receptor-γ coactivator-1α, a transcriptional regulator for mitochondrial biogenesis. In addition, hypoxia-inducible factor-1α, hexokinase, and phosphoglycerate mutase expression declined postbirth, whereas acetylation of these glycolytic enzymes increased. Phosphorylation rather than acetylation of pyruvate dehydrogenase (PDH) increased in 21-day-old hearts, accounting for the low glucose oxidation postbirth. A maturational increase was also observed in succinylation of PDH and LCAD. Collectively, our data are the first suggesting that acetylation and succinylation of the key metabolic enzymes in newborn hearts play a crucial role in cardiac energy metabolism with maturation. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/acetylation-control-of-energy-metabolism-in-newborn-hearts/ .

Isoproterenol stimulates 5′-AMP-activated protein kinase and fatty acid oxidation in neonatal hearts

2010 ◽  
Vol 299 (4) ◽  
pp. H1135-H1145 ◽  
Author(s):  
Jagdip S. Jaswal ◽  
Chad R. Lund ◽  
Wendy Keung ◽  
Donna L. Beker ◽  
Ivan M. Rebeyka ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Oxidation ◽  
Energy Demand ◽  
Glucose Oxidation ◽  
Acid Oxidation ◽  
Acetyl Coa ◽  
Lactate Oxidation ◽  
Major Energy Source ◽  
Amp Activated Protein Kinase

Isoproterenol increases phosphorylation of LKB, 5′-AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC), enzymes involved in regulating fatty acid oxidation. However, inotropic stimulation selectively increases glucose oxidation in adult hearts. In the neonatal heart, fatty acid oxidation becomes a major energy source, while glucose oxidation remains low. This study tested the hypothesis that increased energy demand imposed by isoproterenol originates from fatty acid oxidation, secondary to increased LKB, AMPK, and ACC phosphorylation. Isolated working hearts from 7-day-old rabbits were perfused with Krebs solution (0.4 mM palmitate, 11 mM glucose, 0.5 mM lactate, and 100 mU/l insulin) with or without isoproterenol (300 nM). Isoproterenol increased myocardial O2 consumption (in J·g dry wt−1·min−1; 11.0 ± 1.4, n = 8 vs. 7.5 ± 0.8, n = 6, P < 0.05), and the phosphorylation of LKB (in arbitrary density units; 0.87 ± 0.09, n = 6 vs. 0.59 ± 0.08, n = 6, P < 0.05), AMPK (0.82 ± 0.08, n = 6 vs. 0.51 ± 0.06, n = 6, P < 0.05), and ACC-β (1.47 ± 0.14, n = 6 vs. 0.97 ± 0.07, n = 6, P < 0.05), with a concomitant decrease in malonyl-CoA levels (in nmol/g dry wt; 0.9 ± 0.9, n = 8 vs. 7.5 ± 1.3, n = 8, P < 0.05) and increase in palmitate oxidation (in nmol·g dry wt−1·min−1; 272 ± 45, n = 8 vs. 114 ± 9, n = 6, P < 0.05). Glucose and lactate oxidation were increased (in nmol·g dry wt−1·min−1; 253 ± 75, n = 8 vs. 63 ± 15, n = 9, P < 0.05 and 246 ± 43, n = 8 vs. 82 ± 11, n = 6, P < 0.05, respectively), independent of alterations in pyruvate dehydrogenase phosphorylation, but occurred secondary to a decrease in acetyl-CoA content and acetyl-CoA-to-free CoA ratio. As acetyl-CoA levels decrease in response to isoproterenol, despite an acceleration of the rates of palmitate and carbohydrate oxidation, these data suggest net rates of acetyl-CoA utilization exceed the net rates of acetyl-CoA generation.

Abstract 653: Muscle Ring Finger-1 (MuRF1) Expression Shifts Cardiomyocyte Substrate Utilization from Fatty Acids to Glucose

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Monte S Willis ◽  
Jon Schisler ◽  
Holly McDonough ◽  
Cam Patterson
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Relative Proportion ◽  
Substrate Utilization ◽  
Acid Oxidation ◽  
Protective Mechanism ◽  
Dependent Manner ◽  
Dose Dependent

Previous work has suggested that MuRF1, a cardiac-specific protein, regulates metabolism by its interactions with proteins that regulate ATP transport, glycolysis, and the electron transport chain. We recently identified that MuRF1 is cardioprotective in ischemia reperfusion injury. In the current study, we investigated the effects of MuRF1 expression on metabolic substrate utilization and found that MuRF1 shifts substrate utilization from fatty acids to glucose in a dose-dependent manner. Isolated neonatal ventricular cardiomyocytes were treated with an adenovirus expressing MuRF1 (Ad.MuRF1) or GFP (Ad.GFP) at a range of 0–25 MOI (Multiplicity Of Infection). 14C-Oleate or 14C-glucose were added to cells for 1 hour and 14C-CO2 release was determined using the CO2-trapping method. Trapped 14CO2 and acid soluble metabolites were used to calculate total fatty acid oxidation. Cardiomyocytes treated with 5–25 MOI Ad.MuRF1 demonstrated a dose dependent decrease in fatty acid oxidation of 10.5 +/− 2.3(5 MOI), 8.5 +/− 1.9 (10 MOI), 6.6 +/− 1.6 (15 MOI), and 5.1 +/− 1.3 (25 MOI) nmol oleate/mg protein/h. Compared with control cardiomyocytes treated with 5–25 MOI Ad.GFP (average of 5–25 MOI=13.5 +/− 0.7 nmol oleate/mg protein/h), this represents a 22.2%– 62.2% decrease in fatty acid oxidation. Inversely, glucose oxidation increased with increasing MuRF1 expression. Cardiomyocytes infected with 25 MOI Ad.MuRF1 oxidized 184% more glucose (28.9 +/− 4.6 nmol glucose/mg protein/h) compared to control cells treated with 25 MOI Ad.GFP (15.7 +/− 1.3 nmol glucose/mg protein/h). Increasing MuRF1 expression resulted in no net gain or loss of calculated ATP production (1699 +/− 157 vs. 1480 +/− 188 nmol ATP/mg protein/h). The co-utilization of glucose and fatty acids as substrates for the production of ATP allows the heart to adapt to both environmental stress and disease. Increasing the relative proportion of glucose oxidation in relationship to fatty acids is a known protective mechanism during cardiac stress, and may represent one mechanism by which MuRF1 is cardioprotective.

scholarly journals Effects of milk diets containing beef tallow or coconut oil on the fatty acid metabolism of liver slices from preruminant calves

2000 ◽  
Vol 84 (3) ◽  
pp. 309-318 ◽  
Author(s):  
Benoît Graulet ◽  
Dominique Gruffat-Mouty ◽  
Denys Durand ◽  
Dominique Bauchart
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Beef Tallow ◽  
Neutral Lipids ◽  
Lipid Production ◽  
Coconut Oil ◽  
Acid Oxidation ◽  
Milk Diet ◽  
Liver Slices ◽  
Triacylglycerol Accumulation

Coconut oil (CO) induces a triacylglycerol infiltration in the hepatocytes of preruminant calves when given as the sole source of fat in the milk diet over a long-term period. Metabolic pathways potentially involved in this hepatic triacylglycerol accumulation were studied by in vitro methods on liver slices from preruminant Holstein × Friesian male calves fed a conventional milk diet containing CO (n 5) or beef tallow (BT, n 5) for 19 d. Liver slices were incubated for 12 h in the presence of 0·8 mM-[14C] oleate or -[14C] laurate added to the medium. Fatty acid oxidation was determined by measuring the production of CO2 (total oxidation) and acid-soluble products (partial oxidation). Production of CO2 was 1·7–3·6-fold lower (P 0·0490) and production of acid-soluble products tended to be lower (P = 0·0625) in liver slices of CO- than BT-fed calves. Fatty acid esterification as neutral lipids was 2·6– to 3·1–fold higher (P = 0·0088) in liver slices prepared from calves fed the CO diet compared with calves fed the BT diet. By contrast with what occurs in the liver of rats fed CO, the increase in neutral lipid production did not stimulate VLDL secretion by the hepatocytes of calves fed with CO, leading to a triacylglycerol accumulation in the cytosol. It could be explained by the reduction of fatty acid oxidation favouring esterification in the form of triacylglycerols, in association with a limited availability of triacylglycerols and/or apolipoprotein B for VLDL packaging and subsequent secretion.

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.

scholarly journals Mitochondrial fission governed by Drp1 regulates exogenous fatty acid usage and storage

2020 ◽  
Author(s):  
Jae Eun Song ◽  
Tiago C. Alves ◽  
Bernardo Stutz ◽  
Matija Sestan-Pesa ◽  
Nicole Kilian ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Lipid Droplets ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Fatty Acid Content ◽  
Acid Oxidation ◽  
Exogenous Fatty Acid ◽  
And Storage

ABSTRACTThe bioenergetic function of mitochondrial fission is associated with uncoupled respiration or elimination of damaged mitochondria to maintain a healthy mitochondrial population. In the presence of a high abundance of exogenous fatty acids, cells can either store fatty acids in lipid droplets or oxidize them in mitochondria. Even though carnitine palmitoyltransferase-1 (CPT1) controls the respiratory capacity of mitochondria in fatty acid oxidation, we observed that it did not dictate the balance of storage and usage of lipids in HeLa cells. On the other hand, inhibition of mitochondrial fission by silencing dynamic-related protein 1 (DRP1) resulted in an increase in fatty acid content of lipid droplets and a decrease in fatty acid oxidation. Mitochondrial fission was not only reflective of the amount of exogenous fatty acid being processed by mitochondria, but also found to be actively involved in the distribution of fatty acids between mitochondria and lipid droplets. Our data reveals a novel function for mitochondrial fission in balancing exogenous fatty acids between usage and storage, assigning a role for mitochondrial dynamics in control of intracellular fuel utilization and partitioning.

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