ABSTRACT
The cardiometabolic disease represents a collection of common and interrelated conditions that accelerate the risk of developing cardiovascular diseases. Of importance, metabolic abnormalities are shared among all forms of cardiometabolic diseases. As the heart is one of the major energy-consuming organs in our body, perturbations in cardiac energetics are an important contributor to impaired cardiac function. As such, understanding how the heart’s metabolic profile is altered and the underlying cellular mechanisms that contribute to such changes should help develop therapeutics and/or prevention tactics for cardiomyopathies associated with cardiometabolic diseases. This chapter will focus on two common drivers of cardiometabolic diseases, namely obesity and type 2 diabetes. In both conditions, the heart becomes heavily reliant on fatty acid oxidation for energy production, while the rate of cardiac glucose oxidation dramatically decreases. These changes result in a “metabolic inflexibility” in the heart that can have a detrimental impact on cardiac function. Various molecular mechanisms, such as epigenetics, transcriptional modulations, and post-translational modifications, will be discussed with respect to how they contribute to the altered metabolic state of the heart in obesity and type 2 diabetes. Additionally, several lifestyle interventions, pharmacological approaches, and surgical procedures will be critically appraised in the context of treating obesity and type 2 diabetes. Specifically, the implications of these therapies on cardiac energy metabolism will be discussed, with potential therapeutic strategies proposed for future investigation.
