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During conditions that result in depleted circulating glucose levels, ketone bodies synthesized in the liver are necessary fuel substrates for the brain. In other organs such as the heart, the reliance on ketones for generating energy is less life threatening as the heart can utilize alternative fuel sources such as fatty acids. However, during pathophysiological conditions such as heart failure, cardiac defects in metabolic processes that normally allow for sufficient energy production from fatty acids and carbohydrates contribute to a