Both during normal physiological development as well as in the face of cardiac stress, the heart exhibits enormous plasticity in growth, remodeling, and atrophy. Central to this adaptive ability is the heart’s metabolic capacity to react quickly both anabolically and catabolically in order to maintain cardiac output. In response to hemodynamic stress, the heart adapts to maintain overall contractile function via pathological remodeling that often includes cardiomyocyte hypertrophy as well as changes in cardiomyocyte metabolism that eventually lead to contractile dysfunction and heart failure. It is unclear as to whether the metabolic changes that accompany pathological hypertrophy are adaptive or maladaptive; however, as in most complex biological systems, the answer likely resides somewhere in the middle. Goodwin et al. demonstrated in 1998 that hemodynamic stress increases carbohydrate use for ATP generation and induces cardiac remodeling. Numerous subsequent studies have attributed the change in metabolism and cardiac remodeling to activation of the mammalian (or mechanistic) target of rapamycin (mTOR), a kinase that is a primary regulator of myocardial protein synthesis. Recent experimental models that manipulate cardiac metabolism and mTOR signaling have provided new insights into the relationship between metabolic and structural remodeling (reviewed in detail by Kundu et al.). One hopes that such models will identify metabolic changes that precede remodeling in order to find therapeutic targets for cardiac disease
