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The energy starvation hypothesis proposes that maladaptive metabolic remodeling antedates, initiates, and maintains adverse contractile dysfunction in heart failure (HF). Better understanding of the cardiac metabolic phenotype and metabolic signaling could help identify the role metabolic remodeling plays within HF and the conditions known to transition toward HF, including "pathological" hypertrophy. In this review, we discuss metabolic phenotype and metabolic signaling in the contexts of pathological hypertrophy and HF. We discuss the significance of alterations in energy supply (substrate utilization, oxidative capacity, and phosphotransfer) and energy sensing using observations from human and animal disease models and models of manipulated energy supply/sensing. We aim to provide ways of thinking about metabolic remodeling that center around metabolic flexibility, capacity (reserve), and efficiency rather than around particular substrate preferences or transcriptomic profiles. We show that maladaptive metabolic remodeling takes multiple forms across multiple energy-handling domains. We suggest that lack of metabolic flexibility and reserve (substrate, oxidative, and phosphotransfer) represents a final common denominator ultimately compromising efficiency and contractile reserve in stressful contexts.

Original publication

DOI

10.1152/ajpheart.00731.2016

Type

Journal article

Journal

Am J Physiol Heart Circ Physiol

Publication Date

01/09/2017

Volume

313

Pages

H597 - H616

Keywords

creatine kinase, heart failure, hypertrophy, substrate metabolism, Adaptation, Physiological, Animals, Cardiomegaly, Disease Progression, Energy Metabolism, Heart Failure, Humans, Myocardium, Phenotype