Effect of adrenodemedullation on decline in muscle malonyl-CoA during exercise

1993 ◽  
Vol 74 (5) ◽  
pp. 2548-2551 ◽  
Author(s):  
W. W. Winder ◽  
R. W. Braiden ◽  
D. C. Cartmill ◽  
C. A. Hutber ◽  
J. P. Jones
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Treadmill Running ◽  
Acid Oxidation ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Malonyl Coa ◽  
Exercise Induced ◽  
Rate Limiting

Malonyl-CoA is an inhibitor of carnitine palmitoyltransferase, a rate-limiting enzyme of fatty acid oxidation. Previous studies have indicated that muscle malonyl-CoA declines in rats during treadmill running. This decrease may be important for allowing an increased rate of fatty acid oxidation during prolonged exercise. This study was designed to determine whether epinephrine is essential for inducing the decline in muscle malonyl-CoA during exercise. Male Sprague-Dawley rats underwent adrenodemedullation (ADM) or sham operation. After allowing 3 wk for recovery, rats were killed (pentobarbital anesthesia) at rest or after running at 21 m/min up a 15% grade for 60 min. Red quadriceps malonyl-CoA decreased from 2.6 +/- 0.3 to 0.8 +/- 0.07 nmol/g in sham-operated rats and from 2.2 +/- 0.3 to 0.8 +/- 0.1 nmol/g in ADM rats. White quadriceps malonyl-CoA decreased to similar levels during exercise in both sham-operated and ADM rats. A second experiment on 24-h fasted rats also showed no impairment in the exercise-induced decline in red quadriceps malonyl-CoA as a result of adrenodemedullation. The hormones of the adrenal medulla are therefore unessential for inducing the decline in malonyl-CoA during exercise.

Muscle malonyl-CoA decreases during exercise

1989 ◽  
Vol 67 (6) ◽  
pp. 2230-2233 ◽  
Author(s):  
W. W. Winder ◽  
J. Arogyasami ◽  
R. J. Barton ◽  
I. M. Elayan ◽  
P. R. Vehrs
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Plasma Catecholamines ◽  
Male Rats ◽  
Acid Oxidation ◽  
Glycogen Depletion ◽  
Carnitine Acyltransferase ◽  
Malonyl Coa ◽  
Important Regulator ◽  
Exercise Induced

Malonyl-CoA, the inhibitor of carnitine acyltransferase I, is an important regulator of fatty acid oxidation and ketogenesis in the liver. Muscle carnitine acyltransferase I has previously been reported to be more sensitive to malonyl-CoA inhibition than is liver carnitine acyltransferase I. Fluctuations in malonyl-CoA concentration may therefore be important in regulating the rate of fatty acid oxidation in muscle during exercise. Male rats were anesthetized (pentobarbital via venous catheters) at rest or after 30 min of treadmill exercise (21 m/min, 15% grade). The gastrocnemius/plantaris muscles were frozen at liquid N2 temperature. Muscle malonyl-CoA decreased from 1.66 +/- 0.17 to 0.60 +/- 0.05 nmol/g during the exercise. This change was accompanied by a 31% increase in cAMP in the muscle. The decline in malonyl-CoA occurred before muscle glycogen depletion and before onset of hypoglycemia. Plasma catecholamines, corticosterone, and free fatty acids were all significantly increased during the exercise. This exercise-induced decrease in malonyl-CoA may be important for allowing the increase in muscle fatty acid oxidation during exercise.

2-Mercaptoacetate, an inhibitor of fatty acid oxidation, decreases the membrane potential in rat liver in vivo

1999 ◽  
Vol 277 (1) ◽  
pp. R301-R305 ◽  
Author(s):  
Sandra Boutellier ◽  
Thomas A. Lutz ◽  
Matthias Volkert ◽  
Erwin Scharrer
Keyword(s):  
Fatty Acid ◽  
Membrane Potential ◽  
Food Intake ◽  
Fatty Acid Oxidation ◽  
Intraperitoneal Injection ◽  
Acid Oxidation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Intraportal Infusion

In former work, intraperitoneal injection of 2-mercaptoacetate (MA), an inhibitor of fatty acid oxidation, increased food intake in rats, which was attenuated by hepatic branch vagotomy, and intraportal injection of MA increased the discharge rate in hepatic vagal afferents. In the present study, we investigated, whether intraperitoneal injection or intraportal infusion of MA affects the hepatic membrane potential in rats in vivo. The liver cell membrane potential was measured in anesthetized Sprague-Dawley rats with the microelectrode technique. Intraperitoneal injection of MA at a dose of 800 μmol/kg body wt significantly decreased the hepatocyte membrane potential by 3.8 mV, whereas at a dose of 400 μmol/kg, the depolarization (1.5 mV) of the membrane was not significant. In another strain of Sprague-Dawley rats, however, MA (400 μmol/kg) produced a significant depolarization of the hepatocyte membrane 50 min (2.6 mV) and 2 h (2.9 mV) after intraperitoneal injection. Intraportal infusion of MA (400 μmol/kg) significantly depolarized the membrane 20 and 50 min after infusion by 3.3 and 4.1 mV, respectively. MA at a dose of 800 μmol/kg also depolarized the membrane (4.8 mV after 50 min). These findings in principle are consistent with the “potentiostatic” hypothesis, postulating a link between the hepatic membrane potential, afferent vagal activity, and the control of food intake.

Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism

2005 ◽  
Vol 288 (5) ◽  
pp. C1074-C1082 ◽  
Author(s):  
Timothy R. Koves ◽  
Robert C. Noland ◽  
Andrew L. Bates ◽  
Sarah T. Henes ◽  
Deborah M. Muoio ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Exercise Training ◽  
Fatty Acid Oxidation ◽  
Treadmill Running ◽  
Hill Coefficient ◽  
Acid Oxidation ◽  
Oxidation Rates ◽  
Malonyl Coa ◽  
Mitochondrial Fatty Acid

Skeletal muscle contains two populations of mitochondria that appear to be differentially affected by disease and exercise training. It remains unclear how these mitochondrial subpopulations contribute to fiber type-related and/or training-induced changes in fatty acid oxidation and regulation of carnitine palmitoyltransferase-1β (CPT1β), the enzyme that controls mitochondrial fatty acid uptake in skeletal muscle. To this end, we found that fatty acid oxidation rates were 8.9-fold higher in subsarcolemmal mitochondria (SS) and 5.3-fold higher in intermyofibrillar mitochondria (IMF) that were isolated from red gastrocnemius (RG) compared with white gastrocnemius (WG) muscle, respectively. Malonyl-CoA (10 μM), a potent inhibitor of CPT1β, completely abolished fatty acid oxidation in SS and IMF mitochondria from WG, whereas oxidation rates in the corresponding fractions from RG were inhibited only 89% and 60%, respectively. Endurance training also elicited mitochondrial adaptations that resulted in enhanced fatty acid oxidation capacity. Ten weeks of treadmill running differentially increased palmitate oxidation rates 100% and 46% in SS and IMF mitochondria, respectively. In SS mitochondria, elevated fatty acid oxidation rates were accompanied by a 48% increase in citrate synthase activity but no change in CPT1 activity. Nonlinear regression analyses of mitochondrial fatty acid oxidation rates in the presence of 0–100 μM malonyl-CoA indicated that IC50 values were neither dependent on mitochondrial subpopulation nor affected by exercise training. However, in IMF mitochondria, training reduced the Hill coefficient ( P < 0.05), suggesting altered CPT1β kinetics. These results demonstrate that endurance exercise provokes subpopulation-specific changes in mitochondrial function that are characterized by enhanced fatty acid oxidation and modified CPT1β-malonyl-CoA dynamics.

Hepatic vagotomy effects on metabolic challenges during parenteral nutrition in rats

1994 ◽  
Vol 266 (2) ◽  
pp. R646-R649 ◽  
Author(s):  
J. L. Beverly ◽  
Z. J. Yang ◽  
M. M. Meguid
Keyword(s):  
Fatty Acid ◽  
Parenteral Nutrition ◽  
Fatty Acid Oxidation ◽  
Latin Square ◽  
Plasma Free Fatty Acid ◽  
Acid Oxidation ◽  
Feeding Response ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Hepatic Fatty Acid Oxidation

During parenteral nutrition (PN) glucoprivic-induced feeding appeared to be neutralized by the oxidation of infused fatty acids. With the use of a latin-square design, the feeding response to 2-deoxy-D-glucose (2-DG) and/or 2-mercaptoacetate (MA) was evaluated in male Sprague-Dawley rats with hepatic branch vagotomy (HV) or sham operations (SO). Rats received continuous infusions of 0.9% saline or PN providing 100% of daily caloric needs (PN-100) for four consecutive days. During PN-100, food intake was stimulated by 2-DG in HV rats and when fatty acid oxidation was simultaneously inhibited by MA. 2-DG-induced hyperglycemia was apparent under all conditions. Lipoprivic-induced feeding and increased plasma free fatty acid concentrations were absent in HV rats, whether MA was administered alone or with 2-DG. The feeding response to glucoprivic challenges is influenced by the relative availability of alternate energy sources. The lack of feeding response to 2-DG during PN-100 is mediated by vagal input of hepatic fatty acid oxidation status.

Time course of exercise-induced decline in malonyl-CoA in different muscle types

1990 ◽  
Vol 259 (2) ◽  
pp. E266-E271 ◽  
Author(s):  
W. W. Winder ◽  
J. Arogyasami ◽  
I. M. Elayan ◽  
D. Cartmill
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Time Course ◽  
Exercise Bout ◽  
Male Rats ◽  
Acid Oxidation ◽  
Type I ◽  
Malonyl Coa ◽  
Exercise Induced ◽  
Cpt I

Malonyl-CoA is a potent inhibitor of carnitine palmitoyltransferase I (CPT-I), the rate-limiting enzyme for fatty acid oxidation in mitochondria from liver of fed rats. Malonyl-CoA has also been demonstrated to inhibit skeletal muscle CPT-I. This study was designed to determine the rate of decline in malonyl-CoA in muscle during the course of a prolonged exercise bout. Adult male rats were anesthetized (pentobarbital sodium, intravenously) at rest or after running for 5, 10, 20, 30, 60, or 120 min on a treadmill (21 m/min, 15% grade). Malonyl-CoA was then quantitated in the soleus (type I fibers) and in the superficial white (type IIB) and deep red (type IIA) regions of the quadriceps. Malonyl-CoA decreased in red quadriceps from 2.8 +/- 0.2 to 1.4 +/- 0.2 pmol/mg after 5 min and to 0.9 +/- 0.1 pmol/mg after 20 min of exercise. The concentration of malonyl-CoA remained at this level for the duration of the exercise bout (120 min). In white quadriceps, resting values of malonyl-CoA were lower than in red quadriceps, and a significant decline was not observed until 30 min of exercise. A significant decrease in the soleus was observed after 20 min of exercise. This decline in muscle malonyl-CoA may be an important signal for allowing increased fatty acid oxidation during long-term exercise.

scholarly journals A Low-Carbohydrate Ketogenic Diet and Treadmill Training Enhanced Fatty Acid Oxidation Capacity but Did Not Enhance Maximal Exercise Capacity in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 611
Author(s):  
Sihui Ma ◽  
Jiao Yang ◽  
Takaki Tominaga ◽  
Chunhong Liu ◽  
Katsuhiko Suzuki
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Exercise Capacity ◽  
Ketogenic Diet ◽  
Maximal Exercise ◽  
Treadmill Running ◽  
Acid Oxidation ◽  
Oxidation Capacity ◽  
Low Carbohydrate ◽  
Maximal Exercise Capacity

The low-carbohydrate ketogenic diet (LCKD) is a dietary approach characterized by the intake of high amounts of fat, a balanced amount of protein, and low carbohydrates, which is insufficient for metabolic demands. Previous studies have shown that an LCKD alone may contribute to fatty acid oxidation capacity, along with endurance. In the present study, we combined a 10-week LCKD with an 8-week forced treadmill running program to determine whether training in conjunction with LCKD enhanced fatty acid oxidation capacity, as well as whether the maximal exercise capacity would be affected by an LCKD or training in a mice model. We found that the lipid pool and fatty acid oxidation capacity were both enhanced following the 10-week LCKD. Further, key fatty acid oxidation related genes were upregulated. In contrast, the 8-week training regimen had no effect on fatty acid and ketone body oxidation. Key genes involved in carbohydrate utilization were downregulated in the LCKD groups. However, the improved fatty acid oxidation capacity did not translate into an enhanced maximal exercise capacity. In summary, while favoring the fatty acid oxidation system, an LCKD, alone or combined with training, had no beneficial effects in our intensive exercise-evaluation model. Therefore, an LCKD may be promising to improve endurance in low- to moderate-intensity exercise, and may not be an optimal choice for those partaking in high-intensity exercise.

An explanation for decreased ketogenesis in the liver of the obese Zucker rat

1989 ◽  
Vol 257 (4) ◽  
pp. R822-R828 ◽  
Author(s):  
M. J. Azain ◽  
J. A. Ontko
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Rat Liver ◽  
Intact Cell ◽  
Zucker Rats ◽  
Acid Oxidation ◽  
Palmitate Oxidation ◽  
Malonyl Coa ◽  
Obese Zucker Rats ◽  
Rat Livers

These studies were undertaken to further characterize and explain the differences in hepatic fatty acid metabolism between lean and obese Zucker rats. It was shown that the rate of palmitate or octanoate oxidation and the inhibition of palmitate oxidation by malonyl CoA in mitochondria isolated from lean and obese Zucker rats were similar. Cytochrome oxidase activity was similar in lean and obese rat livers. It was found that the addition of cytosol from the obese rat liver inhibited palmitate oxidation by 20-30% in mitochondria isolated from lean or obese rat livers and thus reproduced the conditions observed in the intact cell. Increased concentrations of metabolites such as malonyl CoA and glycerophosphate in the liver of the obese rat are likely contributors to this inhibitory effect. These results are extrapolated to the intact cell and suggest that decreased hepatic fatty acid oxidation in the obese rat can be accounted for by cytosolic influences on the mitochondria. The decreased rate of fatty acid oxidation observed in the intact hepatocyte or perfused liver cannot be explained by a defect in the capacity of mitochondria to oxidize substrate or by a decrease in mitochondrial number in the obese rat liver.

Higher mitochondrial fatty acid oxidation following intermittent versus continuous endurance exercise training

1998 ◽  
Vol 76 (9) ◽  
pp. 891-894 ◽  
Author(s):  
P D Chilibeck ◽  
G J Bell ◽  
R P Farrar ◽  
T P Martin
Keyword(s):  
Fatty Acid ◽  
Exercise Training ◽  
Fatty Acid Oxidation ◽  
Endurance Exercise ◽  
High Intensity ◽  
Treadmill Running ◽  
Acid Oxidation ◽  
Interval Exercise ◽  
Endurance Exercise Training ◽  
Mitochondrial Fatty Acid

It has been well documented that skeletal muscle fatty acid oxidation can be elevated by continuous endurance exercise training. However, it remains questionable whether similar adaptations can be induced with intermittent interval exercise training. This study was undertaken to directly compare the rates of fatty acid oxidation in isolated subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria following these different exercise training regimes. Mitochondria were isolated from the gastrocnemius-plantaris muscles of male Sprague-Dawley rats following exercise training 6 days per week for 12 weeks. Exercise training consisted of either continuous, submaximal, endurance treadmill running (n = 10) or intermittent, high intensity, interval running (n = 10). Both modes of training enhanced the oxidation of palmityl-carnitine-malate in both mitochondrial populations (p < 0.05). However, the increase associated with the intermittent, high intensity exercise training was significantly greater than that achieved with the continuous exercise training (p < 0.05). Also, the increases associated with the IMF mitochondria were greater than the SS mitochondria (p < 0.05). These data suggest that high intensity, intermittent interval exercise training is more effective for stimulation of fatty acid oxidation than continuous submaximal exercise training and that this adaptation occurs preferentially within IMF mitochondria.Key words: muscle, subsarcolemmal mitochondria, intermyofibrillar mitochondria.

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