Nutrient sensing and utilization: Getting to the heart of metabolic flexibility

A central feature of obesity-related cardiometabolic diseases is the impaired ability to transition between fatty acid and glucose metabolism. This impairment, referred to as "metabolic inflexibility", occurs in a number of tissues, including the heart. Although the heart normally prefers to metabolize fatty acids over glucose, the inability to upregulate glucose metabolism under energetically demanding conditions contributes to a pathological state involving energy imbalance, impaired contractility, and post-translational protein modifications. This review discusses pathophysiologic processes that contribute to cardiac metabolic inflexibility and speculates on the potential physiologic origins that lead to the current state of cardiometabolic disease in an obesogenic environment.