AMPK and metabolic adaptation by the heart to pressure overload

• Published in: American journal of physiology. Heart and circulatory physiology 2007-01, Vol.292 (1), p.H140-H148
• Main Authors: Allard, Michael F, Parsons, Hannah L, Saeedi, Ramesh, Wambolt, Richard B, Brownsey, Roger
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological; AMP-Activated Protein Kinases; Animals; Blood Pressure; Cardiology; Circulatory system; Energy Metabolism; Fatty acids; Fatty Acids - metabolism; Heart; Heart - physiopathology; Hypertrophy, Left Ventricular - physiopathology; Male; Multienzyme Complexes - metabolism; Oxidation; Protein-Serine-Threonine Kinases - metabolism; Rats; Rats, Sprague-Dawley
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00424.2006

1 James Hogg iCapture Centre for Cardiovascular and Respiratory Research, Department of Pathology and Laboratory Medicine, University of British Columbia-St. Paul's Hospital; and 2 Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada Submitted 27 April 2006 ; accepted in final form 15 August 2006 Accelerated glycolysis in hypertrophied hearts may be a compensatory response to reduced energy production from long-chain fatty acid oxidation with 5'-AMP-activated protein kinase (AMPK) functioning as a cellular signal. Therefore, we tested the hypothesis that enhanced fatty acid oxidation improves energy status and normalizes AMPK activity and glycolysis in hypertrophied hearts. Glycolysis, fatty acid oxidation, AMPK activity, and energy status were measured in isolated working hypertrophied and control hearts from aortic-constricted and sham-operated male Sprague-Dawley rats. Hearts from halothane (3–4%)-anesthetized rats were perfused with KH solution containing either palmitate, a long-chain fatty acid, or palmitate plus octanoate, a medium-chain fatty acid whose oxidation is not impaired in hypertrophied hearts. Compared with control, fatty acid oxidation was lower in hypertrophied hearts perfused with palmitate, whereas it increased to similar values in both groups with octanoate plus palmitate. Glycolysis was accelerated in palmitate-perfused hypertrophied hearts and was normalized in hypertrophied hearts by the addition of octanoate. AMPK activity was increased three- to sixfold with palmitate alone and was reduced to control values by octanoate plus palmitate. Myocardial energy status improved with the addition of octanoate but did not differ between groups. Our findings, particularly the correspondence between glycolysis and AMPK activity, provide support for the view that activation of AMPK is responsible, in part, for the acceleration of glycolysis in cardiac hypertrophy. Additionally, they indicate myocardial AMPK is activated by energy state-independent mechanisms in response to pressure overload, demonstrating AMPK is more than a sensor of the heart's energy status. adenosine 5'-monophosphate-activated protein kinase; energy metabolism; cardiac function Address for reprint requests and other correspondence: M. F. Allard, James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Rm 166, St. Paul's Hospital, 1081 Burrard St., Vancouver, BC, Canada V6Z 1Y6 (e-mail: mallard{a