Calcium regulation of glycolysis, glucose oxidation and fatty acid oxidation in the aerobic and ischemic heart

1995 ◽  
Vol 73 (11) ◽  
pp. 1632-1640 ◽  
Author(s):  
Brett Schönekess ◽  
Peter G. Brindley ◽  
Gary O. Lopaschuk
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Glucose Oxidation ◽  
Pyruvate Dehydrogenase Complex ◽  
Dry Weight ◽  
Low Flow ◽  
Acid Oxidation ◽  
Atp Production ◽  
Palmitate Oxidation ◽  
Oxidation Rates

Although Ca2+is an important regulator of energy metabolism, the effects of increasing extracellular [Ca2+] on energy substrate preference are not clear. We determined the relationship between [Ca2+], fatty acids, and ischemia on rates of glycolysis, glucose oxidation, and palmitate oxidation in isolated working rat hearts. Hearts were perfused with Krebs–Henseleit buffer containing 11 mM glucose, 100 μU/mL insulin, and either 1.25 or 2.5 mM Ca2+, in the presence or absence of 1.2 mM palmitate. Rates of glycolysis and glucose oxidation or palmitate oxidation were measured in the hearts using [5-3H,14C(U)]glucose or [1-14C]palmitate, respectively. In the absence of fatty acids, glycolysis and glucose oxidation rates were similar, regardless of whether [Ca2+] was 1.25 or 2.5 mM. Addition of 1.2 mM palmitate to the perfusate of hearts perfused with 1.25 mM Ca2+significantly decreased rates of both glycolysis (from 4623 ± 438 to 1378 ± 238 nmol∙min−1∙g−1dry weight) and glucose oxidation (from 1392 ± 219 to 114 ± 22 nmol∙min−1∙g−1dry weight). When [Ca2+] was increased from 1.25 to 2.5 mM in hearts perfused with 1.2 mM palmitate, glycolysis and glucose oxidation increased by 164 and 271%, respectively, with no change in palmitate oxidation rates. Increasing [Ca2+] from 1.25 to 2.5 mM increased the contribution of glucose to ATP production from 9.3 to 18.7%. When hearts were subjected to low-flow ischemia (by reducing coronary flow to 0.5 mL∙min−1) oxidative metabolism was essentially abolished. Under these conditions, glycolytic rates were not dependent on either [Ca2+] or the presence or absence of fatty acids. These results demonstrate that perfusate [Ca2+] is an important determinant of myocardial glucose metabolism in aerobic hearts, and that glycolysis and glucose oxidation are more responsive to changes in [Ca2+] than is fatty acid oxidation.Key words: β-oxidation, glucose oxidation, pyruvate dehydrogenase complex.

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.

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.

Glycolysis is predominant source of myocardial ATP production immediately after birth

1991 ◽  
Vol 261 (6) ◽  
pp. H1698-H1705 ◽  
Author(s):  
G. D. Lopaschuk ◽  
M. A. Spafford ◽  
D. R. Marsh
Keyword(s):  
Steady State ◽  
Fatty Acid ◽  
Glucose Oxidation ◽  
Glycolytic Flux ◽  
Lactate Oxidation ◽  
Atp Production ◽  
Palmitate Oxidation ◽  
Oxidation Rates ◽  
14Co2 Production ◽  
Pulmonary Arterial

Glycolytic flux, as well as glucose, fatty acid, and lactate oxidation, was determined in isolated working hearts obtained from 1- and 7-day-old rabbits. One-day-old rabbit hearts were perfused via the inferior cava against a constant aortic and pulmonary arterial afterload, whereas hearts from 7-day-old rabbits were perfused via the left atria against a constant aortic afterload. Hearts were perfused with buffer containing 100 microU/ml insulin and either 1) 11 mM [U-14C/2-3H]glucose, 0.4 mM palmitate, 2 mM lactate; 2) 11 mM glucose, 0.4 mM [1-14C]palmitate, 2 mM lactate; or 3) 11 mM glucose, 0.4 mM palmitate, 2 mM [U-14C]lactate. Glycolytic rates (measured as 3H2O production) were high in 1-day-old hearts but decreased by 7 days (from 2,730 +/- 280 to 580 +/- 80 nmol.min-1.g dry wt-1). Rates of glucose oxidation (measured as 14CO2 production) were lower in both 1- and 7-day-old hearts (59 +/- 4.4 and 23 +/- 2 nmol.min-1.g dry wt-1). Palmitate oxidation rates were low in 1-day-old hearts but dramatically increased by 7 days (22.6 +/- 5.6 and 305 +/- 33 nmol oxidized.min-1.g dry wt-1, respectively). In contrast, lactate was readily oxidized by both 1- and 7-day-old hearts (169 +/- 14 and 456 +/- 52 nmol.min-1.g dry wt-1, respectively). In 1-day-old hearts, 44% of steady-state ATP production from exogenous sources were derived from glycolysis, whereas 18, 13, and 25% were derived from glucose, palmitate, and lactate oxidation, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

AMP-activated protein kinase regulation of fatty acid oxidation in the ischaemic heart

2003 ◽  
Vol 31 (1) ◽  
pp. 207-212 ◽  
Author(s):  
T.A. Hopkins ◽  
J.R.B. Dyck ◽  
G.D. Lopaschuk
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Acid Oxidation ◽  
Oxidation Rates ◽  
Ischaemic Damage ◽  
Malonyl Coa ◽  
Amp Activated Protein Kinase

The heart relies predominantly on a balance between fatty acids and glucose to generate its energy supply. There is an important interaction between the metabolic pathways of these two substrates in the heart. When circulating levels of fatty acids are high, fatty acid oxidation can dominate over glucose oxidation as a source of energy through feedback inhibition of the glucose oxidation pathway. Following an ischaemic episode, fatty acid oxidation rates increase further, resulting in an uncoupling between glycolysis and glucose oxidation. This uncoupling results in an increased proton production, which worsens ischaemic damage. Since high rates of fatty acid oxidation can contribute to ischaemic damage by inhibiting glucose oxidation, it is important to maintain proper control of fatty acid oxidation both during and following ischaemia. An important molecule that controls myocardial fatty acid oxidation is malonyl-CoA, which inhibits uptake of fatty acids into the mitochondria. The levels of malonyl-CoA in the heart are controlled both by its synthesis and degradation. Three enzymes, namely AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and malonyl-CoA decarboxylase (MCD), appear to be extremely important in this process. AMPK causes phosphorylation and inhibition of ACC, which reduces the production of malonyl-CoA. In addition, it is suggested that AMPK also phosphorylates and activates MCD, promoting degradation of malonyl-CoA levels. As a result malonyl-CoA levels can be dramatically altered by activation of AMPK. In ischaemia, AMPK is rapidly activated and inhibits ACC, subsequently decreasing malonyl-CoA levels and increasing fatty acid oxidation rates. The consequence of this is a decrease in glucose oxidation rates. In addition to altering malonyl-CoA levels, AMPK can also increase glycolytic rates, resulting in an increased uncoupling of glycolysis from glucose oxidation and an enhanced production of protons and lactate. This decreases cardiac efficiency and contributes to the severity of ischaemic damage. Decreasing the ischaemic-induced activation of AMPK or preventing the downstream decrease in malonyl-CoA levels may be a therapeutic approach to treating ischaemic heart disease.

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.

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 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.

Hepatic alpha 2 mu-globulin: a potential metabolic role in the rat proximal tubule

1996 ◽  
Vol 271 (3) ◽  
pp. F527-F538 ◽  
Author(s):  
S. C. Borkan ◽  
Y. H. Wang ◽  
K. T. Lam ◽  
P. Brecher ◽  
J. H. Schwartz
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Proximal Tubule ◽  
Glucose Oxidation ◽  
Renal Cortex ◽  
Female Rats ◽  
Male Rats ◽  
Normal Female ◽  
Fatty Acid Binding ◽  
Oxidation Rates

In the present study, we provide immunohistochemical and immunologic evidence to localize an abundant, 15.5-kDa protein to the soluble protein fraction of the proximal tubule. This 15.5-kDa protein binds fatty acids in vitro and has identity with amino acids 10-117 of alpha 2 mu-globulin (A2 fragment), a 19-kDa protein synthesized predominantly in the male liver. With reverse transcription-polymerase chain reaction, mRNA for A2 was detected in male liver but not in the male kidney. De novo accumulation of the 15.5-kDa protein was observed in the renal cortex of female rats given intravenous injections of purified 19-kDa protein (A2), suggesting intrarenal processing of the larger protein. The potential role of this protein in the proximal tubule, a site that utilizes fatty acids as an important metabolic substrate, was determined in isolated proximal tubule segments. Fatty acid and glucose oxidation rates were measured in three experimental models in which the 15.5-kDa protein was virtually absent: 1) uninephrectomized male rats treated with deoxycorticosterone acetate and salt, 2) male rats subjected to bilateral adrenalectomy, and 3) normal female rats. In the absence of the 15.5-kDa protein, fatty acid oxidation rates decreased by 30-55%, whereas glucose oxidation significantly increased in all three models. In female renal cortex, depletion of the 15.5-kDa protein was associated with a rise in heart fatty acid binding protein, an alternative intracellular transporter of fatty acids. These data support the hypothesis that a proteolytic cleavage product of hepatic alpha 2 mu-globulin may facilitate the oxidation of oleate, a hydrophobic ligand, in the proximal tubule.

FAT/CD36-null mice reveal that mitochondrial FAT/CD36 is required to upregulate mitochondrial fatty acid oxidation in contracting muscle

2009 ◽  
Vol 297 (4) ◽  
pp. R960-R967 ◽  
Author(s):  
Graham P. Holloway ◽  
Swati S. Jain ◽  
Veronic Bezaire ◽  
Xiao Xia Han ◽  
Jan F. C. Glatz ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Fatty Acid ◽  
Muscle Contraction ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Fatty Acid Transport ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Palmitate Oxidation ◽  
Oxidation Rates ◽  
Mitochondrial Fatty Acid

The plasma membrane fatty acid transport protein FAT/CD36 is also present at the mitochondria, where it may contribute to the regulation of fatty acid oxidation, although this has been challenged. Therefore, we have compared enzyme activities and rates of mitochondrial palmitate oxidation in muscles of wild-type (WT) and FAT/CD36 knockout (KO) mice, at rest and after muscle contraction. In WT and KO mice, carnitine palmitoyltransferase-I, citrate synthase, and β-hydroxyacyl-CoA dehydrogenase activities did not differ in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria of WT and FAT/CD36 KO mice. Basal palmitate oxidation rates were lower ( P < 0.05) in KO mice (SS −18%; IMF −13%). Muscle contraction increased fatty acid oxidation (+18%) and mitochondrial FAT/CD36 protein (+16%) in WT IMF but not in WT SS, or in either mitochondrial subpopulation in KO mice. This revealed that the difference in IMF mitochondrial fatty acid oxidation between WT and KO mice can be increased ∼2.5-fold from 13% under basal conditions to 35% during muscle contraction. The FAT/CD36 inhibitor sulfo- N-succinimidyl oleate (SSO), inhibited palmitate transport across the plasma membrane in WT, but not in KO mice. In contrast, SSO bound to mitochondrial membranes and reduced palmitate oxidation rates to a similar extent in both WT and KO mitochondria (∼80%; P < 0.05). In addition, SSO reduced state III respiration with succinate as a substrate, without altering mitochondrial coupling (P/O ratios). Thus, while SSO inhibits FAT/CD36-mediated palmitate transport at the plasma membrane, SSO has undefined effects on mitochondria. Nevertheless, the KO animals reveal that FAT/CD36 contributes to the regulation of mitochondrial fatty acid oxidation, which is especially important for meeting the increased metabolic demands during muscle contraction.

Sign in / Sign up

Export Citation Format

Share Document