| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA
2 Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA; Nutrition, Case Western Reserve University, Claveland, OH, USA
3 Pediatrics, University of Alberta, Edmonton, Alberta, Canada
4 Nutrition, Case Western Reserve University, Claveland, OH, USA
* To whom correspondence should be addressed. E-mail: wcs4{at}case.edu.
Myocardial fatty acid oxidation is regulated by carnitine palmitoyltransferase I (CPT-I), which is inhibited by malonyl-CoA. Increased cardiac power causes a fall in malonyl-CoA content and accelerated fatty acid oxidation, however, the mechanism for the decrease in malonyl-CoA is unclear. Malonyl-CoA is formed by acetyl-CoA carboxylase (ACC) and degraded by malonyl-CoA decarboxylase (MCD), thus a fall in malonyl-CoA could be due to activation of MCD, inhibition of ACC, or both. This study assessed the effects of increased cardiac power on malonyl-CoA content and ACC and MCD activities. Anesthetized pigs were studied under control (CON; n=7) conditions and during increased cardiac power in response to dobutamine infusion and aortic constriction alone (DOB; n=6), under hyperglycemic conditions (DOB+GLU; n=9), or with the CPT-1 inhibitor oxfenicine (DOB+GLU+OXF; n=9). An increase in cardiac power was accompanied by an increase MVO2, decreased [malonyl-CoA], and increased fatty acid oxidation. There were no differences between CON, DOB, DOB+GLU, and DOB+GLU+OXF in the activity of ACC, or in AMP activated protein kinase, which physiologically inhibits ACC. There were also no differences in the Vmax or Km of MCD. Previous studies demonstrate that AMPK can be inhibited by protein kinase B (PKB), however PKB was activated by dobutamine and the elevated insulin that accompanied hyperglycemia, but there was no effect on AMPK activity. In conclusion, the fall in malonyl-CoA and increase in fatty acid oxidization that occurs with increased cardiac work was not due to inhibition of ACC or activation of MCD, suggesting alternative regulatory mechanisms for the work-induced decrease in the malonyl-CoA concentration.
This article has been cited by other articles:
|
|
 |
|
  L. Zhou, H. Huang, C. L. Yuan, W. Keung, G. D. Lopaschuk, and W. C. Stanley Metabolic response to an acute jump in cardiac workload: effects on malonyl-CoA, mechanical efficiency, and fatty acid oxidation Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H954 - H960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zhou, M. E. Cabrera, H. Huang, C. L. Yuan, D. K. Monika, N. Sharma, F. Bian, and W. C. Stanley Parallel activation of mitochondrial oxidative metabolism with increased cardiac energy expenditure is not dependent on fatty acid oxidation in pigs J. Physiol., March 15, 2007; 579(3): 811 - 821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. An and B. Rodrigues Role of changes in cardiac metabolism in development of diabetic cardiomyopathy Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1489 - H1506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhou, M. E. Cabrera, I. C. Okere, N. Sharma, and W. C. Stanley Regulation of myocardial substrate metabolism during increased energy expenditure: insights from computational studies Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1036 - H1046. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
