Covalent activation of heart AMP‐activated protein kinase in response to physiological concentrations of long‐chain fatty acids
- 10 May 2004
- journal article
- Published by Wiley in JBIC Journal of Biological Inorganic Chemistry
- Vol. 271 (11), 2215-2224
- https://doi.org/10.1111/j.1432-1033.2004.04151.x
Abstract
Rat hearts were perfused for 1 h with 5 mm glucose with or without palmitate or oleate at concentrations characteristic of the fasting state. The inclusion of fatty acids resulted in increased activities of the alpha-1 or the alpha-2 isoforms of AMP-activated protein kinase (AMPK), increased phosphorylation of acetyl-CoA carboxylase and a decrease in the tissue content of malonyl-CoA. Activation of AMPK was not accompanied by any changes in the tissue contents of ATP, ADP, AMP, phosphocreatine or creatine. Palmitate increased phosphorylation of Thr172 within AMPK alpha-subunits and the activation by palmitate of both AMPK isoforms was abolished by protein phosphatase 2C leading to the conclusion that exposure to fatty acid caused activation of an AMPK kinase or inhibition of an AMPK phosphatase. In vivo, 24 h of starvation also increased heart AMPK activity and Thr172 phosphorylation of AMPK alpha-subunits. Perfusion with insulin decreased both alpha-1 and alpha-2 AMPK activities and increased malonyl-CoA content. Palmitate prevented both of these effects. Perfusion with epinephrine decreased malonyl-CoA content without an effect on AMPK activity but prevented the activation of AMPK by palmitate. The concept is discussed that activation of AMPK by an unknown fatty acid-driven signalling process provides a mechanism for a 'feed-forward' activation of fatty acid oxidation.Keywords
This publication has 70 references indexed in Scilit:
- AMP-activated protein kinase, super metabolic regulatorBiochemical Society Transactions, 2003
- New targets of AMP-activated protein kinaseBiochemical Society Transactions, 2003
- Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinaseNature, 2002
- The α1 and α2 isoforms of the AMP‐activated protein kinase have similar activities in rat liver but exhibit differences in substrate specificity in vitroFEBS Letters, 1996
- Characterization of 5′AMP-activated protein kinase activity in the heart and its role in inhibiting acetyl-CoA carboxylase during reperfusion following ischemiaBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1996
- Negative interactions between phosphorylation of acetyl‐CoA carboxylase by the cyclic AMP‐dependent and AMP‐activated protein kinasesFEBS Letters, 1988
- A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesisFEBS Letters, 1987
- Relation between lipolysis and glycolysis during ischemia in the isolated rat heartBasic Research in Cardiology, 1986
- Carnitine palmitoyltransferase and carnitine octanoyltransferase activities in liver, kidney cortex, adipocyte, lactating mammary gland, skeletal muscle and heartFEBS Letters, 1981
- THE GLUCOSE FATTY-ACID CYCLE ITS ROLE IN INSULIN SENSITIVITY AND THE METABOLIC DISTURBANCES OF DIABETES MELLITUSThe Lancet, 1963