In the case of pathological forms of cardiac hypertrophy, such as occurs with chronic pressure overload, the heart undergoes well-defined fuel utilization changes. 1–3 The normal adult heart uses mitochondrial fatty acid oxidation (FAO) as its chief source of ATP production. With pathological hypertrophic growth, FAO rates fall concordant with an increase in glycolysis and glucose oxidation. Several lines of evidence suggest that changes in myocardial fuel utilization impact the hypertrophic growth response and subsequent remodeling en route to heart failure. For example, inborn errors in mitochondrial FAO enzymes in humans often result in a hypertrophic form of cardiomyopathy. 4 Conversely, mice with cardiac-specific deletion of acetyl-CoA carboxylase 2 (ACC2), which results in constitutively high cardiac FAO rates, are protected against the development of cardiac hypertrophy and pathological remodeling in response to pressure overload or angiotensin II infusion in mice. 5 ACC2 generates malonyl-CoA, a key negative regulator of fatty acid import into the mitochondrion at the step catalyzed by carnitine palmitoyltransferase I. These observations raise the intriguing possibility that reduced flux through FAO and increased glucose utilization is required for the cardiac hypertrophic response. Consistent with this general concept, it is well known that cancer cells often require anaerobic glycolysis (Warburg effect) 6 to maintain high rates of cellular proliferation.