AMPK signalling and the control of substrate use in the heart

All mammalian cells rely on adenosine triphosphate (ATP) to maintain function and for survival. The heart has the highest basal ATP demand of any organ due to the necessity for continuous contraction. As such, the ability of the cardiomyocyte to monitor cellular energy status and adapt the supply of substrates to match the energy demand is crucial. One important serine/threonine protein kinase that monitors cellular energy status in the heart is adenosine monophosphate activated protein kinase (AMPK). AMPK is also a key enzyme that controls multiple catabolic and anabolic biochemical pathways in the heart and indirectly plays a crucial role in regulating cardiac function in both physiological and pathophysiological conditions. Herein, we review the involvement of AMPK in myocardial fatty acid and glucose transport and utilization, as it relates to basal cardiac function. We also assess the literature amassed on cardiac AMPK and discuss the controversies surrounding the role of AMPK in physiological and pathophysiological processes in the heart. The work reviewed herein also emphasizes areas that require further investigation for the purpose of eventually translating this information into improved patient care.

► We review the role AMPK plays in cardiac lipid transport and utilization.
► We review the role AMPK plays in cardiac glucose transport and utilization.
► We examine the role of AMPK signalling and substrate use in ischemia and reperfusion.
► We examine the role of AMPK signalling and substrate use in cardiac hypertrophy.
► We discuss future perspectives on the role of AMPK in cardiac substrate use in health and disease.