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While ketone oxidation is essential in the brain during prolonged fasting\/starvation, other organs such as skeletal muscle and the heart also use ketones as metabolic substrates. Additionally, \u03b2OHB-mediated molecular signaling events occur in heart and skeletal muscle cells, and via metabolism and\/or signaling, ketones may contribute to optimal skeletal muscle health and cardiac function. Of importance, when the use of ketones for ATP production and\/or as signaling molecules becomes disturbed in the presence of underlying obesity, type 2 diabetes, and\/or cardiovascular diseases, these changes may contribute to cardiometabolic disease. As a result of these disturbances in cardiometabolic disease, multiple approaches have been used to elevate circulating ketones with the goal of optimizing either ketone metabolism or ketone-mediated signaling. 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