scholarly journals Changes in oleic acid oxidation and incorporation into lipids of differentiating L6 myoblasts cultured in normal or fatty acid-supplemented growth medium

1987 ◽  
Vol 244 (3) ◽  
pp. 743-748 ◽  
Author(s):  
V S Sauro ◽  
K P Strickland
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Neutral Lipid ◽  
Fatty Acid Oxidation ◽  
Growth Medium ◽  
Normal Growth ◽  
Acid Oxidation ◽  
Exogenous Fatty Acid ◽  
Oxidation Rates ◽  
Cells Cultured

L6 myoblasts accumulate large stores of neutral lipid (predominantly triacylglycerol) when cultured in fatty acid-supplemented growth medium. No accumulation of neutral lipid was evident in myotubes (differentiated myoblasts) when treated similarly. Triacylglycerol accumulation was rapid and dependent on exogenous fatty acid concentration. Triacylglycerol content in myoblasts cultured in fatty acid-supplemented growth medium was approx. 3-fold higher than that in myotubes treated similarly and 2-3-fold higher than that in myoblasts cultured in normal growth medium. Incorporation studies using [I-14C]oleic acid showed that myoblasts and myotubes take up exogenous fatty acid at similar rates. However, cells cultured in fatty acid-supplemented growth medium remove more exogenous fatty acid than do cells cultured in normal growth medium. Over 90% of the incorporated label was found in phospholipid and triacylglycerol fractions in all situations studied. Myoblasts incorporated a more significant proportion (P less than 0.001) of label into triacylglycerol compared with that of myotubes. No differences in fatty acid oxidation rates were detected when differentiating L6 cells cultured in normal growth medium were compared with those cultured in fatty acid-supplemented growth medium. However, fatty acid oxidation rates were observed to increase 3-5-fold upon myoblast differentiation. We conclude that there is a marked change in the pattern of lipid metabolism when myoblasts (primarily triacylglycerol-synthesizing cells) differentiate into myotubes (primarily phospholipid-synthesizing cells). Understanding these changes, which coincide with normal muscle development, may be important, since a defect in this natural switch could explain the observed accumulation of lipid in muscle characteristic of some of the muscular dystrophies and other lipid-storage myopathies.

379-P: Aldose Reductase Inhibition by AT-001 Prevents Diabetic Cardiomyopathy via Reducing Myocardial Fatty Acid Oxidation Rates

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 379-P
Author(s):  
KESHAV GOPAL ◽  
QUTUBA G. KARWI ◽  
SEYED AMIRHOSSEIN TABATABAEI DAKHILI ◽  
CORY S. WAGG ◽  
RICCARDO PERFETTI ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Aldose Reductase ◽  
Diabetic Cardiomyopathy ◽  
Acid Oxidation ◽  
Myocardial Fatty Acid ◽  
Aldose Reductase Inhibition ◽  
Oxidation Rates

Abstract 282: Adropin Enhancement of Cardiac Insulin Sensitivity and Inhibition of Fatty Acid Oxidation are Associated With Improvement of Cardiac Function and Efficiency in Hearts From Fasted Mice

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Tariq R Altamimi ◽  
Arata Fukushima ◽  
Liyan Zhang ◽  
Su Gao ◽  
Abhishek Gupta ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Diabetic Cardiomyopathy ◽  
Insulin Signaling ◽  
Plasma Levels ◽  
Acid Oxidation ◽  
Post Translational Modification ◽  
Cardiac Efficiency ◽  
Oxidation Rates ◽  
Cardiac Energy

Impaired cardiac insulin signaling and high cardiac fatty acid oxidation rates are characteristics of diabetic cardiomyopathy. Potential roles for liver-derived metabolic factors in mediating cardiac energy homeostasis are underappreciated. Plasma levels of adropin, a liver secreted peptide, increase during feeding and decrease during fasting and diabetes. In skeletal muscle, adropin preferentially promotes glucose over fatty acid oxidation. We therefore determined what effect adropin has on cardiac energy metabolism, insulin signaling and cardiac efficiency. C57Bl/6 mice were fasted to accentuate the differences in adropin plasma levels between animals injected 3 times over 24 hr with either vehicle or adropin (450 nmol/kg i.p.). Despite fasting-induced predominance of fatty acid oxidation measured in isolated working hearts, insulin inhibition of fatty acid oxidation was re-established in adropin-treated mice (from 1022±143 to 517±56 nmol. g dry wt -1 . min -1 , p <0.05) compared to vehicle-treated mice (from 757±104 to 818±103 nmol. g dry wt -1 . min -1 ). Adropin-treated mice hearts showed higher cardiac work over the course of perfusion (p<0.05 vs. vehicle), which was accompanied by improved cardiac efficiency and enhanced phosphorylation of insulin signaling enzymes (tyrosine-IRS-1, AS160, p<0.05). Acute addition of adropin (2nM) to isolated working hearts from non-fasting mice showed a robust stimulation of glucose oxidation compared to vehicle-treated hearts (3025±401 vs 1708±292 nmol. g dry wt -1 . min -1 , p<0.05, respectively) with a corresponding inhibition of palmitate oxidation (325±61 vs 731±160 nmol. g dry wt -1 . min -1 , p<0.05, respectively), even in the presence of insulin. Acute adropin addition to hearts also increased IRS-1 tyrosine-phosphorylation as well as Akt, and GSK3β phosphorylation (p<0.05), suggesting acute receptor- and/or post-translational modification-mediated mechanisms. These results suggest adropin as a putative candidate for the treatment of diabetic cardiomyopathy.

Impact of 1 wk of diabetes on the regulation of myocardial carbohydrate and fatty acid oxidation

1999 ◽  
Vol 277 (2) ◽  
pp. E342-E351 ◽  
Author(s):  
John C. Chatham ◽  
Zhi-Ping Gao ◽  
John R. Forder
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fold Increase ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Acid Oxidation ◽  
Oxidation Rates ◽  
Tissue Extracts ◽  
Isotopomer Analysis ◽  
C Nmr

The aim of this study was to investigate the effect of increasing exogenous palmitate concentration on carbohydrate and palmitate oxidation in hearts from control and 1-wk diabetic rats. Hearts were perfused with glucose, [3-13C]lactate, and [U-13C]palmitate. Substrate oxidation rates were determined by combining13C-NMR glutamate isotopomer analysis of tissue extracts with measurements of oxygen consumption. Carbohydrate oxidation was markedly depressed after diabetes in the presence of low (0.1 mM) but not high (1.0 mM) palmitate concentration. Increasing exogenous palmitate concentration 10-fold resulted in a 7-fold increase in the contribution of palmitate to energy production in controls but only a 30% increase in the diabetic group. Consequently, at 0.1 mM palmitate, the rate of fatty acid oxidation was higher in the diabetic group than in controls; however, at 1.0 mM fatty acid oxidation, it was significantly depressed. Therefore, after 1 wk of diabetes, the major differences in carbohydrate and fatty acid metabolism occur primarily at low rather than high exogenous palmitate concentration.

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/ .

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.

Effect of phosphorylation by AMP-activated protein kinase on palmitoyl-CoA inhibition of skeletal muscle acetyl-CoA carboxylase

2005 ◽  
Vol 98 (4) ◽  
pp. 1221-1227 ◽  
Author(s):  
D. S. Rubink ◽  
W. W. Winder
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Oxidation Rates ◽  
Malonyl Coa ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) has previously been demonstrated to phosphorylate and inactivate skeletal muscle acetyl-CoA carboxylase (ACC), the enzyme responsible for synthesis of malonyl-CoA, an inhibitor of carnitine palmitoyltransferase 1 and fatty acid oxidation. Contraction-induced activation of AMPK with subsequent phosphorylation/inactivation of ACC has been postulated to be responsible in part for the increase in fatty acid oxidation that occurs in muscle during exercise. These studies were designed to answer the question: Does phosphorylation of ACC by AMPK make palmitoyl-CoA a more effective inhibitor of ACC? Purified rat muscle ACC was subjected to phosphorylation by AMPK. Activity was determined on nonphosphorylated and phosphorylated ACC preparations at acetyl-CoA concentrations ranging from 2 to 500 μM and at palmitoyl-CoA concentrations ranging from 0 to 100 μM. Phosphorylation resulted in a significant decline in the substrate saturation curve at all palmitoyl-CoA concentrations. The inhibitor constant for palmitoyl-CoA inhibition of ACC was reduced from 1.7 ± 0.25 to 0.85 ± 0.13 μM as a consequence of phosphorylation. At 0.5 mM citrate, ACC activity was reduced to 13% of control values in response to the combination of phosphorylation and 10 μM palmitoyl-CoA. Skeletal muscle ACC is more potently inhibited by palmitoyl-CoA after having been phosphorylated by AMPK. This may contribute to low-muscle malonyl-CoA values and increasing fatty acid oxidation rates during long-term exercise when plasma fatty acid concentrations are elevated.

Abstract 15649: Pharmacological Inhibition of Aldose Reductase by AT001 Prevents Abnormal Cardiac Energy Metabolism and Improves Heart Function in an Animal Model of Diabetic Cardiomyopathy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Keshav Gopal ◽  
Qutuba Karwi ◽  
Seyed Amirhossein Tabatabaei Dakhili ◽  
Riccardo Perfetti ◽  
Ravichandran Ramasamy ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Energy Metabolism ◽  
Fatty Acid Oxidation ◽  
Diabetic Cardiomyopathy ◽  
Acid Oxidation ◽  
Cardiac Energetics ◽  
Cardiac Efficiency ◽  
Oxidation Rates ◽  
Cardiac Energy Metabolism ◽  
Cardiac Energy

Introduction: Diabetic Cardiomyopathy (DCM) is a major cause of death in people with type 2 diabetes (T2D). Alterations in cardiac energy metabolism including increased fatty acid oxidation rates and reduced glucose oxidation rates are key contributing factors to the development of DCM. Studies have shown that Aldose Reductase (AR), an enzyme activated under hyperglycemic conditions, can modulate myocardial glucose and fatty acid oxidation, and promotes cardiac dysfunction. Hypothesis: Pharmacological inhibition of AR using a next-generation inhibitor AT-001, can mitigate DCM in mice by modulating cardiac energy metabolism and improving cardiac efficiency. Methods: Male human AR overexpressing (hAR-Tg) and C57BL/6J (Control) mice were subjected to experimental T2D (high-fat diet [60% kcal from lard] for 10-wk with a single intraperitoneal streptozotocin injection of 75 mg/kg) and treated for the last 3-wk with AT-001 (40mg/kg/day) or vehicle via oral gavage. Cardiac energy metabolism and in vivo cardiac function were assessed via isolated working heart perfusions and ultrasound echocardiography, respectively. Results: AT-001 treatment significantly improved cardiac energetics in a murine model of DCM (hAR-Tg mice with T2D). Particularly, AT-001-treated mice exhibited decreased cardiac fatty acid oxidation rates compared to the vehicle-treated mice (342 ± 53 vs 964 ± 130 nmol/min/g dry wt.). Concurrently, there was a significant decrease in cardiac oxygen consumption in the AT-001-treated compared to the vehicle-treated mice (41 ± 12 vs 60 ± 11 μmol/min/g dry wt.), suggesting increased cardiac efficiency. Furthermore, treatment with AT-001 prevented cardiac structural and functional abnormalities present in DCM, including diastolic dysfunction as reflected by an increase in the tissue Doppler E’/A’ ratio and decrease in E/E’ ratio. Moreover, AT-001 treatment prevented cardiac hypertrophy as reflected by a decrease in LV mass in AT-001-treated mice. Conclusions: AR inhibition with AT-001 prevents cardiac structural and functional abnormalities in a mouse model of DCM, and normalizes cardiac energetics by shifting cardiac metabolism towards a non-diabetic metabolic state.

Regulation of myocardial fatty acid oxidation by substrate supply

2001 ◽  
Vol 281 (4) ◽  
pp. H1561-H1567 ◽  
Author(s):  
Sarah L. Longnus ◽  
Richard B. Wambolt ◽  
Rick L. Barr ◽  
Gary D. Lopaschuk ◽  
Michael F. Allard
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Acetyl Coa ◽  
Regulatory Pathways ◽  
Oxidation Rates ◽  
Substrate Supply ◽  
Exogenous Substrate ◽  
Malonyl Coa ◽  
Myocardial Substrate

We tested the hypothesis that myocardial substrate supply regulates fatty acid oxidation independent of changes in acetyl-CoA carboxylase (ACC) and 5′-AMP-activated protein kinase (AMPK) activities. Fatty acid oxidation was measured in isolated working rat hearts exposed to different concentrations of exogenous long-chain (0.4 or 1.2 mM palmitate) or medium-chain (0.6 or 2.4 mM octanoate) fatty acids. Fatty acid oxidation was increased with increasing exogenous substrate concentration in both palmitate and octanoate groups. Malonyl-CoA content only rose as acetyl-CoA supply from octanoate oxidation increased. The increases in octanoate oxidation and malonyl-CoA content were independent of changes in ACC and AMPK activity, except that ACC activity increased with very high acetyl-CoA supply levels. Our data suggest that myocardial substrate supply is the primary mechanism responsible for alterations in fatty acid oxidation rates under nonstressful conditions and when substrates are present at physiological concentrations. More extreme variations in substrate supply lead to changes in fatty acid oxidation by the additional involvement of intracellular regulatory pathways.

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