| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Cell Biology and Neurosciences, Rutgers University, Piscataway, New Jersey 08854; and 2 Department of Zoology, Brigham Young University, Provo, Utah 84602
 |
ABSTRACT |
|---|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
5-Aminoimidazole-4-carboxamide
1-
-D-ribofuranoside
(AICAR) is taken up by perfused skeletal muscle and
phosphorylated to form
5-aminoimidazole-4-carboxamide-1--D-ribofuraosyl-5'-monophosphate (analog of 5'-AMP) with consequent activation of AMP-activated protein kinase, phosphorylation of acetyl-CoA carboxylase, decrease in
malonyl-CoA, and increase in fatty acid oxidation. This
study was designed to determine the effect of increasing levels of
palmitate on the rate of fatty acid oxidation. Malonyl-CoA
concentration was manipulated with AICAR at different palmitate
concentrations. Rat hindlimbs were perfused with Krebs-Henseleit
bicarbonate containing 4% bovine serum albumin, washed bovine red
cells, 200 µU/ml insulin, 10 mM glucose, and different concentrations
of palmitate (0.1-1.0 mM) without or with AICAR (2.0 mM).
Perfusion with medium containing AICAR was found to activate
AMP-activated protein kinase in skeletal muscle, inactivate acetyl-CoA
carboxylase, and decrease malonyl-CoA at all concentrations of
palmitate. The rate of palmitate oxidation increased as a function of
palmitate concentration in both the presence and absence of AICAR but
was always higher in the presence of AICAR. These results provide
additional evidence that malonyl-CoA is an important regulator of the
rate of fatty acid oxidation at palmitate concentrations in the
physiological range.
acetyl-CoA carboxylase; 5-aminoimidazole-4-carboxamide
1--D-ribofuranoside; adenosine 5'-monophosphate-activated protein kinase; fatty acid
oxidation
| |
INTRODUCTION |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
CONSIDERABLE ATTENTION has been given to the study of
fuel selection by resting and contracting skeletal muscle, yet much uncertainty exists with regard to specific mechanisms (5, 6, 17, 20,
22). When both carbohydrate and fatty acids are available to the
muscle, what determines how much of each substrate will be utilized for
ATP synthesis? The rate of fatty acid oxidation by skeletal muscle is
considered to be governed in part by malonyl-CoA, an inhibitor of
carnitine palmitoyl transferase 1 (CPT-1) (4, 8, 15, 20, 22). CPT-1 is
essential for transferring long-chain fatty acyl-CoA into the
mitochondria where complete oxidation can occur (8). A recent study in
this laboratory (10) demonstrated that 5-aminoimidazole-4-carboxamide
1--D-ribofuranoside (AICAR) is taken up by perfused skeletal muscle and phosphorylated to form
5-aminoimidazole-4-carboxamide-1--D-ribofuraosyl-5'-monophosphate (ZMP; analog of 5'-AMP) with consequent activation
of AMP-activated protein kinase (AMPK), phosphorylation of acetyl-CoA
carboxylase (ACC), decrease in malonyl-CoA, and increase in fatty acid
oxidation. These changes mimic those seen in muscles during exercise or
in response to electrical stimulation (7, 21-23, 25). Thus, when malonyl-CoA was decreased artificially by use of AICAR, the rate of
fatty acid oxidation was observed to increase. In that study, the fatty
acid concentration in the perfusion medium was low (0.15 mM), and the
contribution of fatty acid oxidation to total oxygen consumption was
relatively small. We postulated that larger contributions would be
observed at higher plasma free fatty acid (FFA) concentrations. This
study was designed to determine the influence of artificially reducing
muscle malonyl-CoA concentrations (using AICAR) on the rate of fatty
acid oxidation at three different fatty acid concentrations.
| |
METHODS |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
Animals. Male Sprague-Dawley rats (Sasco, Wilmington, MA) were housed in individual cages in a temperature- (20-22°C) and light-controlled (12:12-h light-dark cycle) room. Rats were fed ad libitum with Harlan Teklad rodent diet (Madison, WI).
Hindlimb perfusion. The protocol for hindlimb perfusion was approved by the Institutional Animal Care and Use Committee. Rats were anesthetized with pentobarbital sodium (60 mg/kg, ip). Catheters were inserted into the abdominal aorta and inferior vena cava, and tips were advanced to the level of the left iliac artery and vein as described previously by Gorski et al. (3). Vessels to the tail and the right hindlimb were ligated. Skin was removed from the left hindlimb. The exposed muscles were kept moist with gauze wetted with warm Krebs-Henseleit bicarbonate (KHB). After flushing vessels with KHB plus heparin (80 USP units, ia), we perfused the left hindlimb with medium (37°C) composed of washed bovine erythrocytes and KHB containing 4 g/100 ml bovine serum albumin (Sigma Chemical, St. Louis, MO), 200 µU/ml insulin (Humulin, Eli Lilly), and 10 mM glucose with or without AICAR. The bovine serum albumin was previously treated with charcoal and dialyzed extensively to remove low-molecular-weight substances. Sodium palmitate (Sigma Chemical) was placed in 50 ml of KHB, heated to ~50°C, mixed, and added to KHB-albumin. The mixture was then stirred overnight at room temperature to allow the palmitate to complex with the albumin. The clear solution was then frozen until the day of the assay. After it was thawed and mixed, the KHB-albumin was filtered sequentially through 5-, 1-, and 0.45-µm filters on the day of the perfusion just before combination with the erythrocytes. The hematocrit after addition of all components to the medium was ~41.
The perfusions were carried out in a Plexiglas perfusion chamber (37°C) similar to that described by Gorski et al. (3). The medium was oxygenated as it traversed a Silastic tubing coil (6 m, 0.16 cm ID, 0.24 cm OD) in a 1-liter chamber equilibrated with 95% O2-5% CO2. Rats were killed with an overdose of pentobarbital sodium once the perfusion started. Hindlimbs were initially perfused at a rate of 3 ml/min for ~5 min. The rate was then increased to 6 ml/min and sustained throughout the experiment. This flow rate yielded hindlimb perfusion pressures that were in the physiological range (75-100 mmHg). The medium was not recirculated. Hindlimbs were perfused with medium containing 0.1, 0.4, or 1.0 mM palmitate without AICAR or with 2 mM AICAR for 70 min. The labeled palmitate (1.6 µCi of [1-14C]palmitic acid/100 ml perfusate in KHB-albumin) was added to the medium at the beginning of the perfusion. Samples of medium were collected from a port between the oxygenation chamber and the arterial catheter (referred to as the arterial sample) and from the venous catheter (referred to as the venous sample). 14CO2 was quantitated in 5-ml arterial and 5-ml venous samples at 10, 25, 40, 55, and 70 min after exposure to AICAR or vehicle by the method described previously (10). Briefly, a filter paper wick (1 × 2 cm) was glued to a cap from a 20-ml glass liquid-scintillation vial. The wick was saturated with 2-aminoethanol (0.075 ml) immediately before sample collection. Samples (5 ml) of media were collected anaerobically and immediately added to the vials containing 1 ml of 4.5-M lactic acid. Vials were immediately capped and incubated for 20-24 h to allow the 14CO2 to be absorbed on the wick. The wicks were then quickly transferred to another scintillation vial. EcoLite (ICN, Irvine, CA) was added immediately, and the vials were kept in the dark 2 days before quantitation of radioactivity. The palmitate oxidation rate was calculated by dividing the venous-arterial difference in radioactivity (disintegrations/min), appearing as 14CO2 by the specific radioactivity of palmitate (disintegrations · min
1 · nmol1),
and multiplying by the flow rate. Results are expressed as nanomoles
per left perfused hindlimb per minute. The amount of oxygen required to
completely oxidize the palmitate was calculated from the stoichiometry
of the palmitate oxidation equation (i.e., 23 mol of molecular oxygen
are required to oxidize 1 mol of palmitate). Arterial and venous
samples were also taken at the same intervals for determination of
oxygen consumption.
At the end of the perfusion period, the gastrocnemius-plantaris muscle
group was quickly removed and clamp-frozen by using stainless steel
block tongs at liquid nitrogen temperature.
Analytic methods.
Cell-free perfusate was collected by centrifugation of arterial and
venous samples for measurement of FFA concentration (12) and for
fractional extraction of labeled palmitate. Perfusate samples were kept
at 
20°C until they were analyzed. Immediately after
collection, oxygen hemoglobin saturation and hemoglobin concentration
were determined in arterial and venous samples with an OSM 2 Hemoximeter (Radiometer, Copenhagen, Denmark) for calculation of oxygen
consumption. Hemoglobin concentration averaged 15.3 ± 0.2 g/100 ml
of medium.
70°C until analysis. AICAR, ATP,
ADP, ZTP, and ZMP were determined by using a Beckman HPLC system
(supported by System Gold software) by a modification of the method
described by Sabina et al. (14). Briefly, we used a Hichrom P10SAX
column (0.45 × 25 cm; DyChrom, Santa Clara, CA) with a
P10SAX-10C5 guard column. At a flow rate of 2 ml/min, the elution
begins with 100% buffer A (5 mM
NH4H2PO4,
pH 2.8) and 0% buffer B (750 mM
NH4H2PO4, pH 3.9). Buffer B is increased
linearly to 9.3% over a 14-min period. Then over the next 36 min
buffer B is increased to 100% in a
linear gradient. AMPK activity (2, 25) and citrate-dependence curves
for ACC activity (25) were determined by using ammonium sulfate
precipitates from homogenates prepared from the powdered (under liquid
nitrogen) muscles as described previously. Curves were analyzed and
fitted to the Hill equation by using Grafit (Sigma Chemical).
Results are expressed as means ± SE. Statistically significant
differences (P < 0.05) between
groups were determined by using ANOVA and Fisher's least significant
difference test.
| |
RESULTS |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
Control rats weighed 417 ± 8 g, and AICAR-perfused rats weighed 409 ± 8 g on the day of the experiment.
Values for muscle content of ADP, ATP, ZMP, and ZTP for hindlimbs perfused with no AICAR or with 2.0 mM of AICAR at different fatty acid concentrations for 70 min are shown in Table 1. Note that ATP and ADP are unaffected by the AICAR treatment. ZMP, the analog of 5'-AMP, increased to ~1.4 mM in the AICAR-perfused muscles.
|
Figure 1 shows that AMPK activity was significantly increased in the AICAR-perfused muscles at all concentrations of palmitate. The ACC activity at 0.2 mM citrate was markedly decreased in the AICAR-perfused muscles compared with that in controls at all palmitate concentrations. Figure 2 demonstrates the changes in kinetic properties of ACC in the AICAR-perfused hindlimb muscle compared with that in controls. Maximal velocity for ACC was decreased, and the activation constant for citrate activation was increased in response to AICAR (Table 2).
|
|
|
The time course of palmitate oxidation at the three different palmitate concentrations with or without AICAR is shown in Fig. 3. A progressive increase in 14CO2 production by the hindlimb occurred after exposure to AICAR. A statistically significant difference (P < 0.05) was noted between AICAR-perfused and control hindlimbs within 25 min of exposure to AICAR at two of the three palmitate concentrations, with a trend in the other (0.1 mM).
|
In hindlimbs perfused without AICAR, malonyl-CoA was significantly decreased at the higher palmitate concentrations (Fig. 4) compared with that at the 0.1-mM palmitate perfusion. Malonyl-CoA was significantly decreased in AICAR-perfused hindlimbs at all palmitate concentrations.
|
Figure 4 also shows that fatty acid oxidation by the perfused hindlimb at the 70-min time point is increased in response to AICAR. At this time point, with ANOVA and Fisher's least significant difference test, the difference between control and AICAR-perfused hindlimbs was statistically significant (P < 0.05) at 0.4 and 1.0 mM palmitate but not at 0.1 mM palmitate (P = 0.07).
The fractional uptake of palmitate was not significantly different in AICAR-perfused vs. controls at any of the three palmitate concentrations (Table 3). Thus the difference in the rate of palmitate oxidation was not due to a difference in uptake into the muscle caused by AICAR. Similarly, oxygen consumption was not significantly different in AICAR-perfused vs. controls at any of the palmitate concentrations. The percentage of total oxygen consumption required to completely oxidize palmitate increased at 1 mM palmitate in the absence of AICAR and was further increased by the presence of AICAR at 0.4 and 1.0 mM palmitate.
|
| |
DISCUSSION |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
In isolated skeletal muscle mitochondria, the oxidation of palmitate is dependent on the presence of carnitine and CoA (11). Without carnitine, the rate of oxidation of palmitate is only a small fraction of that seen in the presence of carnitine, thus demonstrating the importance of the CPT-1 enzyme for governing the rate of long-chain fatty acid oxidation. Molé et al. (11) also demonstrated an increase in palmitate oxidation rate as a function of palmitate concentration. Turcotte et al. (19) later showed oxidation of palmitate by isolated-perfused hindlimb to be dependent on palmitate concentration at concentrations up to 2 mM. Romijn et al. (13) observed that the oxidation of fatty acids by exercising human subjects appears to be limited to some extent by fatty acid availability at high work rates. Sidossis et al. (16) provided evidence that CPT-1 may be rate-limiting in resting human subjects when availability of carbohydrate (and presumably malonyl-CoA) is increased. Thus the oxidation of palmitate can be influenced by several factors, including carnitine, palmitate, CoA, and malonyl-CoA concentrations, all of which may influence flux through the carnitine palmitoyl-transferase system.
In the isolated-perfused hindlimb, the rate of oxidation of labeled palmitate appears to be limited by two factors: fatty acid concentration in the perfusion medium and whether or not CPT-1 is inhibited by malonyl-CoA. Previous work in this laboratory has demonstrated that palmitoyl-CoA can inhibit the muscle isoform of ACC (18). This may be the reason for the reduction in malonyl-CoA in the control hindlimb perfusions at 0.4 and 1.0 mM palmitate. This reduction in malonyl-CoA is not accompanied by a significant decline in measured ACC activity. The effect of palmitoyl-CoA is allosteric in nature and would not be detected in the ACC activity measurements. The ACC is isolated from muscle by ammonium sulfate precipitation, and it is unlikely that palmitoyl-CoA would be precipitated by this procedure and would, therefore, not be present in high concentration in the final ACC reaction mix. The resuspended ammonium sulfate precipitate is also diluted 1:20 in the final reaction mixture, further reducing the likelihood of palmitoyl-CoA derived from the muscle extract influencing the reaction rate. In the perfused muscle, however, elevated palmitoyl-CoA very likely would inhibit the ACC allosterically.
In the control hindlimbs perfused with medium containing 0.4 and 1.0 mM palmitate, the malonyl-CoA concentration was not significantly different, yet the palmitate oxidation rate was higher at 1.0 than at 0.4 mM. The rate of formation of palmitoyl-carnitine would be expected to be dependent on the concentration of substrates, palmitoyl-CoA and carnitine. In addition, because palmitoyl-CoA and malonyl-CoA appear to compete for the active site (at least in liver mitochondria) of CPT-1 (cf. Ref. 8), an increase in palmitoyl-CoA secondary to an increase in palmitate concentration might be expected to make malonyl-CoA inhibition less effective. When muscle malonyl-CoA was further reduced by perfusion of the muscle with AICAR, marked increases in the palmitate oxidation rate occurred, particularly at 0.4 and 1.0 mM palmitate.
AICAR was previously shown to cause a significant decrease in malonyl-CoA in perfused hindlimb muscle (10). Concurrently, an increase in AMPK activity was observed, along with inactivation of ACC, coupled with distinct changes in kinetic properties of ACC. The maximal velocity is decreased and the activation constant for citrate activation of ACC is markedly increased in AICAR-perfused hindlimb muscle. The net effect of these kinetic changes is virtual inactivation of ACC at physiological citrate concentrations. The kinetic changes seen in ACC in response to AICAR are similar to those seen when ACC is phosphorylated by AMPK in vitro, thus providing indirect evidence that ACC is phosphorylated by AMPK in response to AICAR. These changes are also identical to those observed in muscle of rats run on the treadmill or in muscles stimulated to contract in situ (21, 25). Thus perfusion of the hindlimb muscles with AICAR simulates the effect of contraction on this control system without changing oxygen consumption. The rate of fatty acid oxidation may then be examined at different malonyl-CoA concentrations.
These data indicate that, even in resting rat muscle, the rate of fatty acid oxidation is limited by malonyl-CoA inhibition of CPT-1, even at a high plasma fatty acid concentration. If energy demand were increased by muscle contraction, flux through the CPT-1 reaction would therefore limit the rate of fatty acid oxidation unless malonyl-CoA were reduced. Thus the contraction-induced activation of AMPK with consequent decrease in ACC activity and malonyl-CoA concentration would appear to be essential for allowing increased rates of fatty acid oxidation during exercise. This control system could be thought of as a way to couple increased fatty acid oxidation with muscle contraction. This system is similar to the calcium-induced activation of phosphorylase kinase in contracting muscle, allowing phosphorylation and activation of phosphorylase and consequent increase in glycogenolysis to occur concurrently with muscle contraction. Evidence has also recently been presented indicating that activation of AMPK (using AICAR) in the isolated-perfused hindlimb triggers an increase in glucose uptake by the muscle (10). Phosphorylation of undefined proteins of the GLUT-4 translocation pathway by AMPK has been hypothesized to be involved in inducing the insulin-like effect of muscle contraction (10). All these mechanisms increase the availability of long-chain fatty acids and glucose for oxidation and allow an increased rate of ATP production by the contracting muscle.
As noted in Fig. 3, the fatty acid oxidation rate, estimated by 14CO2 production from [14C]palmitate, increases with time during the perfusion, particularly in the AICAR-perfused muscles. In our previous study (10), the malonyl-CoA content of the muscle was found to decrease within 15 min of exposure to AICAR. Time is required to equilibrate the interstitial space and sacroplasmic palmitate pools, the sarcoplasmic pool of palmitoyl-CoA, the mitochondrial pool of palmitoyl-carnitine and palmitoyl-CoA, and the mitochondrial pool of acetyl-CoA. The 14CO2 derived from [14C]palmitoyl-CoA oxidation enters mitochondrial and then sarcoplasmic CO2-bicarbonate pools, eventually reaching the interstitial and vascular spaces. Finally, the sample is obtained as the medium exits the muscle. It is very likely that the actual rate of palmitate oxidation increases rapidly after the malonyl-CoA concentration and is reduced by AICAR, but this change in oxidation rate is not detected instantaneously due to slow equilibration of all pools to a new steady state. It is not possible to obtain an estimate of instantaneous change in fatty acid oxidation rate by using this system.
The palmitate concentrations utilized in this study span the physiological range. Plasma FFA concentration in resting fed rats is near the 0.1-mM range (25). An overnight fast would increase plasma FFA to ~0.4 mM (26). At the end of a prolonged exercise bout in fed rats or after a few minutes of exercise in fasted rats, the plasma FFA would be in the 1-mM range (1, 24).
In this study, concentrations of both glucose and insulin were certainly on the high side of the physiological range. These concentrations were utilized for the purpose of having a wide range of malonyl-CoA concentrations at the different fatty acid concentrations. It is likely that, if conditions of fasting or prolonged exercise were reproduced, i.e., along with elevated concentration of fatty acids, the concentration of insulin and glucose were reduced in the medium, then even higher rates of fatty acid oxidation might be expected.
The increase in ZMP, which activates AMPK and initiates the cascade of events resulting in an increased rate of fatty acid oxidation, could also be involved in causing other metabolic changes in the cell. The increase in ZMP could, for example, activate phosphorylase (cf. Ref. 27) and influence any other enzyme normally affected by 5'-AMP.
In summary, the stimulation of fatty acid oxidation observed with AICAR-induced reduction in malonyl-CoA at low fatty acid concentrations reported previously is even more marked at 0.4 and 1.0 mM. These data provide additional evidence that malonyl-CoA is an important regulator of long-chain fatty acid oxidation in skeletal muscle.
| |
ACKNOWLEDGEMENTS |
|---|
Technical assistance was provided by P. Bennion, A. Christian, B. Holmes, and C. Carlson.
| |
FOOTNOTES |
|---|
This work was supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant AR-41438 (to W. W. Winder). G. F. Merrill was a visiting professor in the Department of Zoology at Brigham Young University during these experiments.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests: W. W. Winder, 545 WIDB, Dept. of Zoology, Brigham Young Univ., Provo, UT 84602 (E-mail: william_winder{at}byu.edu).
Received 21 March 1998; accepted in final form 25 June 1998.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
1.
Beattie, M. A.,
and
W. W. Winder.
Attenuation of postexercise ketosis in fasted endurance-trained rats.
Am. J. Physiol.
248 (Regulatory Integrative Comp. Physiol. 17):
R63-R67,
1985.
2.
Davies, S. P.,
D. Carling,
and
D. G. Hardie.
Tissue distribution of the AMP-activated protein kinase and lack of activation by cyclic-AMP-dependent protein kinase, studied using a specific and sensitive peptide assay.
Eur. J. Biochem.
186:
123-128,
1989[Medline].
3.
Gorski, J.,
D. A. Hood,
and
R. L. Terjung.
Blood flow distribution in tissues of perfused rat hindlimb preparations.
Am. J. Physiol.
250 (Endocrinol. Metab. 13):
E441-E448,
1986
4.
Hardie, D. G.,
and
D. Carling.
The AMP-activated protein kinase
fuel gauge of the mammalian cell?
Eur. J. Biochem.
246:
259-273,
1997[Medline].
5.
Holloszy, J. O.,
and
W. M. Kohrt.
Regulation of carbohydrate and fat metabolism during and after exercise.
Annu. Rev. Nutr.
16:
121-138,
1996[Medline].
6.
Hultman, E.
Pyruvate dehydrogenase as a regulator of substrate utilization in skeletal muscle.
In: Biochemistry of Exercise IX, edited by R. J. Maughan,
and S. M. Shirreffs. Champaign, IL: Human Kinetics, 1996, p. 157-171.
7.
Hutber, C. A.,
D. G. Hardie,
and
W. W. Winder.
Electrical stimulation inactivates muscle acetyl-CoA carboxylase and increases AMP-activated protein kinase.
Am. J. Physiol.
272 (Endocrinol. Metab. 35):
E262-E266,
1997
8.
McGarry, J. D.,
and
N. F. Brown.
The mitochondrial carnitine palmitoyltransferase system from concept to molecular analysis.
Eur. J. Biochem.
244:
1-14,
1997[Medline].
9.
McGarry, J. D.,
M. J. Stark,
and
D. W. Foster.
Hepatic malonyl-CoA levels of fed, fasted and diabetic rats as measured using a simple radioisotopic assay.
J. Biol. Chem.
253:
8291-8293,
1978
10.
Merrill, G. F.,
E. J. Kurth,
D. G. Hardie,
and
W. W. Winder.
AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle.
Am. J. Physiol.
273 (Endocrinol. Metab. 36):
E1107-E1112,
1997.
11.
Molé, P. A.,
L. B. Oscai,
and
J. O. Holloszy.
Adaptation of muscle to exercise. Increase in levels of palmityl CoA synthetase, carnitine palmityltransferase, and palmityl CoA dehydrogenase, and in the capacity to oxidize fatty acids.
J. Clin. Invest.
50:
2323-2330,
1971.
12.
Novak, M.
Colorimetric ultramicromethod for the determination of free fatty acids.
J. Lipid Res.
6:
431-433,
1965[Abstract].
13.
Romijn, J. A.,
E. F. Coyle,
L. S. Sidossis,
X.-J. Zhang,
and
R. R. Wolfe.
Relationship between fatty acid delivery and fatty acid oxidation during strenuous exercise.
J. Appl. Physiol.
79:
1939-1945,
1995
14.
Sabina, R. L.,
K. H. Kernstine,
R. L. Boyd,
E. W. Holmes,
and
J. L. Swain.
Metabolism of 5-amino-4-imidazolecarboxamide riboside in cardiac and skeletal muscle.
J. Biol. Chem.
257:
10178-10183,
1982
15.
Saha, A. K.,
D. Vavvas,
T. G. Kurowski,
A. Apazidis,
L. Witters,
E. Shafrir,
and
N. B. Ruderman.
Malonyl-CoA regulation in skeletal muscle: its link to cell citrate and the glucose-fatty acid cycle.
Am. J. Physiol.
272 (Endocrinol. Metab. 35):
E641-E648,
1997
16.
Sidossis, L. S.,
C. A. Stuart,
G. I. Shulman,
G. D. Lopaschuk,
and
R. R. Wolfe.
Glucose plus insulin regulate fat oxidation by controlling the rate of fatty acid entry into the mitochondria.
J. Clin. Invest.
98:
2244-2250,
1996[Medline].
17.
Spriet, L. L.,
and
D. J. Dyck.
The glucose-fatty acid cycle in skeletal muscle at rest and during exercise.
In: Biochemistry of Exercise IX, edited by R. J. Maughan,
and S. M. Shirreffs. Champaign, IL: Human Kinetics, 1996, p. 127-155.
18.
Trumble, G. E.,
M. A. Smith,
and
W. W. Winder.
Purification and characterization of rat skeletal muscle acetyl-CoA carboxylase.
Eur. J. Biochem.
231:
192-198,
1995[Medline].
19.
Turcotte, L. P.,
P. J. L. Hespel,
T. E. Graham,
and
E. A. Richter.
Impaired plasma FFA oxidation imposed by extreme CHO deficiency in contracting rat skeletal muscle.
J. Appl. Physiol.
77:
517-525,
1994
20.
Van der Vusse, G. J.,
and
R. S. Reneman.
Lipid metabolism in muscle.
In: Handbook of Physiology. Exercise: Regulation and Integration of Multiple Systems. Bethesda, MD: Am. Physiol. Soc., 1996, sect. 12, chapt. 21, p. 952-994.
21.
Vavvas, D.,
A. Apazidis,
A. K. Saha,
J. Gamble,
A. Patel,
B. E. Kemp,
L. A. Witters,
and
N. B. Ruderman.
Contraction-induced changes in acetyl-CoA carboxylase and 5'-AMP-activated kinase in skeletal muscle.
J. Biol. Chem.
272:
13255-13261,
1997
22.
Winder, W. W.
Malonyl-CoARegulator of fatty acid oxidation in muscle during exercise.
Exerc. Sport Sci. Rev.
26:
117-132,
1998[Medline].
23.
Winder, W. W.,
J. Arogyasami,
I. M. Elayan,
and
D. Cartmill.
Time course of the exercise-induced decline in malonyl-CoA in different muscle types.
Am. J. Physiol.
259 (Endocrinol. Metab. 22):
E266-E271,
1990
24.
Winder, W. W.,
K. M. Baldwin,
and
J. O. Holloszy.
Exercise-induced increase in the capacity of rat skeletal muscle to oxidize ketones.
Can. J. Physiol. Pharmacol.
53:
86-91,
1975[Medline].
25.
Winder, W. W.,
and
D. G. Hardie.
Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise.
Am. J. Physiol.
270 (Endocrinol. Metab. 33):
E299-E304,
1996
26.
Winder, W. W.,
P. S. MacLean,
J. C. Lucas,
J. E. Fernley,
and
G. E. Trumble.
Effect of fasting and refeeding on acetyl-CoA carboxylase in rat hindlimb muscle.
J. Appl. Physiol.
78:
578-582,
1995
27.
Young, M. E.,
G. K. Radda,
and
B. Leighton.
Activation of glycogen phosphorylase and glycogenolysis in rat skeletal muscle by AICARan activator of AMP-activated protein kinase.
FEBS Lett.
382:
43-47,
1996[Medline].
This article has been cited by other articles:
|
|
 |
|
  L. P Turcotte and J. S Fisher Skeletal Muscle Insulin Resistance: Roles of Fatty Acid Metabolism and Exercise Physical Therapy, November 1, 2008; 88(11): 1279 - 1296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Raney and L. P. Turcotte Evidence for the involvement of CaMKII and AMPK in Ca2+-dependent signaling pathways regulating FA uptake and oxidation in contracting rodent muscle J Appl Physiol, May 1, 2008; 104(5): 1366 - 1373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Thomson, J. D. Brown, N. Fillmore, B. M. Condon, H-J. Kim, J. R. Barrow, and W. W. Winder LKB1 and the regulation of malonyl-CoA and fatty acid oxidation in muscle Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1572 - E1579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Rizki, L. Arnaboldi, B. Gabrielli, J. Yan, G. S. Lee, R. K. Ng, S. M. Turner, T. M. Badger, R. E. Pitas, and J. J. Maher Mice fed a lipogenic methionine-choline-deficient diet develop hypermetabolism coincident with hepatic suppression of SCD-1 J. Lipid Res., October 1, 2006; 47(10): 2280 - 2290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Jorgensen, E. A. Richter, and J. F. P. Wojtaszewski Role of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise J. Physiol., July 1, 2006; 574(1): 17 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Rubink and W. W. Winder Effect of phosphorylation by AMP-activated protein kinase on palmitoyl-CoA inhibition of skeletal muscle acetyl-CoA carboxylase J Appl Physiol, April 1, 2005; 98(4): 1221 - 1227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Park, S. R. Paulsen, S. R. Gammon, K. J. Mustard, D. G. Hardie, and W. W. Winder Effects of thyroid state on AMP-activated protein kinase and acetyl-CoA carboxylase expression in muscle J Appl Physiol, December 1, 2002; 93(6): 2081 - 2088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Park, S. R. Gammon, J. D. Knippers, S. R. Paulsen, D. S. Rubink, and W. W. Winder Phosphorylation-activity relationships of AMPK and acetyl-CoA carboxylase in muscle J Appl Physiol, June 1, 2002; 92(6): 2475 - 2482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. McGarry Banting Lecture 2001: Dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes Diabetes, January 1, 2002; 51(1): 7 - 18. [Full Text] [PDF]
|
|
|
|
|
|
W. W. Winder Energy-sensing and signaling by AMP-activated protein kinase in skeletal muscle J Appl Physiol, September 1, 2001; 91(3): 1017 - 1028. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Young, G. W. Goodwin, J. Ying, P. Guthrie, C. R. Wilson, F. A. Laws, and H. Taegtmeyer Regulation of cardiac and skeletal muscle malonyl-CoA decarboxylase by fatty acids Am J Physiol Endocrinol Metab, March 1, 2001; 280(3): E471 - E479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. W. Winder and B. F. Holmes Insulin stimulation of glucose uptake fails to decrease palmitate oxidation in muscle if AMPK is activated J Appl Physiol, December 1, 2000; 89(6): 2430 - 2437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. W. Winder and D. G. Hardie AMP-activated protein kinase, a metabolic master switch: possible roles in Type 2 diabetes Am J Physiol Endocrinol Metab, July 1, 1999; 277(1): E1 - E10. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
