The role of cardiac energy metabolism in cardiac hypertrophy and failure

In mammalian heart, incessant production of cellular energy is vital for maintaining continuous mechanical pumping function providing the body for oxygen and nutrients. To ensure this essential function, cardiac muscle adapt to increased energy demand or compromised energy supply by reprogramming the network of genes whose products are necessary to match the production of energy to consumption. Failure in this regulation leads to severe cardiac dysfunction and has been associated with cardiac pathogenesis including cardiac hypertrophy, failure and diabetes. Metabolic adaptations are induced by network of transcriptional pathways that are activated by a variety of factors such as hormones, nutrients, second messengers and oxygen. The metabolic phenotype of the heart is maintained by pathways controlling transcriptional regulators, which include peroxisome proliferator-activated receptors, estrogen-related receptors and nuclear respiratory factors, as well as their common coactivator protein peroxisome proliferator-activated receptor γ coactivator 1. These central regulators of gene expression are complemented with factors such as hypoxia inducible factor 1, which is activated in insufficient oxygenation of the tissue. Here, we discuss how these pathways relate to the cardiac metabolism and how they interact with pathways controlling the contractile phenotype of the heart.