scholarly journals LPL/AQP7/GPD2 promotes glycerol metabolism under hypoxia and prevents cardiac dysfunction during ischemia.

2020 ◽  
Author(s):  
Sohta Ishihama ◽  
Tatsuya Yoshida ◽  
Satoya Yoshida ◽  
Noriyuki Ouchi ◽  
Yu Mori ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cardiac Dysfunction ◽  
Myocardial Infarct ◽  
Atp Synthesis ◽  
Glycerol Metabolism ◽  
Dihydroxyacetone Phosphate ◽  
Myocardial Infarct Size ◽  
Glucose And Lipid Metabolism ◽  
Acute Mi ◽  
Glycerol 3 Phosphate Dehydrogenase

Abstract Fatty acid constitutes a major energy substrate in the heart to fuel contraction under aerobic conditions. Ischemia downregulates fatty acid metabolism to adapt to the limited oxygen supply and makes glucose the preferred substrate. However, the mechanism of the myocardial metabolic shift during ischemia remains unknown. Here, we show that cardiomyocyte secretion of lipoprotein lipase (LPL), a principal enzyme that converts triglycerides to free fatty acids and glycerol, increased during myocardial infarction (MI). Cardiomyocyte-specific LPL deficiency enhanced cardiac dysfunction and apoptosis following MI. Deficiency of aquaporin 7 (AQP7), a glycerol channel in cardiomyocytes, increased the myocardial infarct size and apoptosis in response to ischemia. Ischemic conditions activated glycerol-3-phosphate dehydrogenase 2 (GPD2), which converts glycerol-3-phosphate into dihydroxyacetone phosphate to facilitate ATP synthesis from glycerol. Conversely, GPD2 deficiency exacerbated cardiac dysfunction after acute MI. Together, these results identify that LPL/AQP7/GPD2-mediated glycerol metabolism plays an important role to bridge glucose and lipid metabolism in MI and prevent myocardial ischemia-related damage.

scholarly journals Fatty-acid-binding protein as a plasma marker for the estimation of myocardial infarct size in humans.

Heart ◽  
1994 ◽  
Vol 71 (2) ◽  
pp. 135-140 ◽  
Author(s):  
J. F. Glatz ◽  
A. H. Kleine ◽  
F. A. van Nieuwenhoven ◽  
W. T. Hermens ◽  
M. P. van Dieijen-Visser ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Infarct Size ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Plasma Marker

scholarly journals Uncoupling effect of polyunsaturated fatty acid deficiency in isolated rat hepatocytes:effect on glycerol metabolism

1996 ◽  
Vol 317 (3) ◽  
pp. 667-674 ◽  
Author(s):  
Marie-Astrid PIQUET ◽  
Eric FONTAINE ◽  
Brigitte SIBILLE ◽  
Céline FILIPPI ◽  
Christiane KERIEL ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Dehydrogenase Activity ◽  
Potassium Cyanide ◽  
Glycerol Metabolism ◽  
Glycolytic Flux ◽  
Isolated Rat Hepatocytes ◽  
Intact Cells ◽  
Glycerol 3 Phosphate Dehydrogenase ◽  
Isolated Rat ◽  
Deficient Group

The effects of a 4-week deficiency in polyunsaturated fatty acids (PUFA) in isolated rat hepatocytes have been investigated for oxidative phosphorylation and fatty acid, dihydroxyacetone (DHA) or glycerol metabolism. Oxygen uptake was significantly increased (by 20%) with or without fatty acid addition (octanoate or oleate) in the PUFA-deficient group compared with controls. The effect persisted after oligomycin addition but not after that of potassium cyanide, leading to the conclusion that, in these intact cells, the mitochondria were uncoupled. The PUFA-deficient group exhibited a significant decrease in the cytosolic ATP/ADP ratio, whereas the mitochondrial ratio was not affected. PUFA deficiency led to a 16% decrease in DHA metabolism owing to a 34% decrease in glycerol kinase activity; the significant decrease in the ATP/ADP ratio was accompanied by an increase in the fractional glycolytic flux. In contrast, glycerol metabolism was significantly enhanced in the PUFA-deficient group. The role of the glycerol 3-phosphate dehydrogenase step in this stimulation was evidenced in hepatocytes perifused with glycerol and octanoate in the presence of increased concentrations of 2,4-dinitrophenol (Dnp): uncoupling with Dnp led to an enhancement of glycerol metabolism, as found in PUFA deficiency, although it was more pronounced than in controls. The matrix/cytosol gradients for redox potential and ATP/ADP ratio were lower in cells from PUFA-deficient rats, suggesting a decreased mitochondrial membrane potential in accordance with the uncoupling effect. Moreover, a doubling of the mitochondrial glycerol 3-phosphate dehydrogenase activity in the PUFA-deficient group compared with controls led us to conclude that the activation of glycerol metabolism is the consequence of two mitochondrial effects: uncoupling and an increase in glycerol 3-phosphate dehydrogenase activity.

scholarly journals Inhibition of Fatty Acid Metabolism Increases EPA and DHA Levels and Protects against Myocardial Ischaemia-Reperfusion Injury in Zucker Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Janis Kuka ◽  
Marina Makrecka-Kuka ◽  
Karlis Vilks ◽  
Stanislava Korzh ◽  
Helena Cirule ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Plasma Insulin ◽  
Myocardial Infarct ◽  
Zucker Rats ◽  
Acid Oxidation ◽  
Myocardial Infarct Size ◽  
Metabolome Analysis ◽  
Plasma Insulin Concentration ◽  
Fatty Acid Utilization ◽  
Long Chain

Long-chain ω-3 polyunsaturated fatty acids (PUFAs) are known to induce cardiometabolic benefits, but the metabolic pathways of their biosynthesis ensuring sufficient bioavailability require further investigation. Here, we show that a pharmacological decrease in overall fatty acid utilization promotes an increase in the levels of PUFAs and attenuates cardiometabolic disturbances in a Zucker rat metabolic syndrome model. Metabolome analysis showed that inhibition of fatty acid utilization by methyl-GBB increased the concentration of PUFAs but not the total fatty acid levels in plasma. Insulin sensitivity was improved, and the plasma insulin concentration was decreased. Overall, pharmacological modulation of fatty acid handling preserved cardiac glucose and pyruvate oxidation, protected mitochondrial functionality by decreasing long-chain acylcarnitine levels, and decreased myocardial infarct size twofold. Our work shows that partial pharmacological inhibition of fatty acid oxidation is a novel approach to selectively increase the levels of PUFAs and modulate lipid handling to prevent cardiometabolic disturbances.

Preserved recovery of cardiac function following ischemia–reperfusion in mice lacking SIRT3

2016 ◽  
Vol 94 (1) ◽  
pp. 72-80 ◽  
Author(s):  
Christoph Koentges ◽  
Katharina Pfeil ◽  
Maximilian Meyer-Steenbuck ◽  
Achim Lother ◽  
Michael M. Hoffmann ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Mitochondrial Permeability Transition ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Atp Synthesis ◽  
Left Ventricular ◽  
Rate Pressure Product ◽  
Myocardial Infarct Size ◽  
Cardiac Power

Lack of the mitochondrial deacetylase sirtuin 3 (SIRT3) impairs mitochondrial function and increases the susceptibility to induction of the mitochondrial permeability transition pore. Because these alterations contribute to myocardial ischemia–reperfusion (IR) injury, we hypothesized that SIRT3 deficiency may increase cardiac injury following myocardial IR. Hearts of 10-week-old mice were perfused in the isolated working mode and subjected to 17.5 min of global no-flow ischemia, followed by 30 min of reperfusion. Measurements before ischemia revealed a decrease in cardiac power (–20%) and rate pressure product (–15%) in SIRT3−/− mice. Mitochondrial state 3 respiration (–15%), ATP synthesis (–39%), and ATP/O ratios (–29%) were decreased in hearts of SIRT3−/− mice. However, percent recovery of cardiac power (WT 94% ± 9%; SIRT3−/− 89% ± 9%) and rate pressure product (WT 89% ± 16%; SIRT3−/− 96% ± 3%) following IR was similar in both groups. Myocardial infarct size was not increased in SIRT3−/− mice following permanent ligation of the left anterior descending coronary artery (LAD). Left ventricular pressure and dP/dtmax, and mitochondrial respiration and ATP synthesis were not different between groups following LAD ligation. Thus, despite pre-existing defects in cardiac function and mitochondrial respiratory capacity in SIRT3−/− mice, SIRT3 deficiency does not additionally impair cardiac function following IR or following myocardial infarction.

scholarly journals Tripartite Regulation of the glpFKD Operon Involved in Glycerol Catabolism by GylR, Crp, and SigF in Mycobacterium smegmatis

2019 ◽  
Vol 201 (24) ◽  
Author(s):  
Hyun-Ju Bong ◽  
Eon-Min Ko ◽  
Su-Yeon Song ◽  
In-Jeong Ko ◽  
Jeong-Il Oh
Keyword(s):  
Energy State ◽  
Transcriptional Activator ◽  
Glycerol Kinase ◽  
Receptor Protein ◽  
Upstream Region ◽  
Glycerol Metabolism ◽  
Dihydroxyacetone Phosphate ◽  
Content Type ◽  
Cellular Energy ◽  
Glycerol 3 Phosphate Dehydrogenase

ABSTRACT The glpD (MSMEG_6761) gene encoding glycerol-3-phosphate dehydrogenase was shown to be crucial for M. smegmatis to utilize glycerol as the sole carbon source. The glpD gene likely forms the glpFKD operon together with glpF and glpK, encoding a glycerol facilitator and glycerol kinase, respectively. The gylR (MSMEG_6757) gene, whose product belongs to the IclR family of transcriptional regulators, was identified 182 bp upstream of glpF. It was demonstrated that GylR serves as a transcriptional activator and is involved in the induction of glpFKD expression in the presence of glycerol. Three GylR-binding sites with the consensus sequence (GKTCGRC-N3-GYCGAMC) were identified in the upstream region of glpF by DNase I footprinting analysis. The presence of glycerol-3-phosphate was shown to decrease the binding affinity of GylR to the glpF upstream region with changes in the quaternary structure of GylR from tetramer to dimer. Besides GylR, cAMP receptor protein (Crp) and an alternative sigma factor, SigF, are also implicated in the regulation of glpFKD expression. Crp functions as a repressor, while SigF induces expression of glpFKD under energy-limiting conditions. In conclusion, we suggest here that the glpFKD operon is under the tripartite control of GylR, SigF, and Crp, which enables M. smegmatis to integrate the availability of glycerol, cellular energy state, and cellular levels of cAMP to exquisitely control expression of the glpFKD operon involved in glycerol metabolism. IMPORTANCE Using genetic approaches, we first revealed that glycerol is catabolized through the glycolytic pathway after conversion to dihydroxyacetone phosphate in two sequential reactions catalyzed by glycerol kinase (GlpK) and flavin adenine dinucleotide (FAD)-containing glycerol-3-phosphate dehydrogenase (GlpD) in M. smegmatis. Our study also revealed that in addition to the GylR transcriptional activator that mediates the induction of the glpFKD operon by glycerol, the operon is regulated by SigF and Crp, which reflect the cellular energy state and cAMP level, respectively.

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