Lipid in the midst of metabolic remodeling – Therapeutic implications for the failing heart

A healthy heart relies on an intact cardiac lipid metabolism. Fatty acids represent the major source for ATP production in the heart. Not less importantly, lipids are directly involved in critical processes such as cell growth, proliferation, and cell death by functioning as building blocks or signaling molecules. In the development of heart failure, perturbations in fatty acid utilization impair cardiac energetics. Furthermore, they may affect glucose and amino acid metabolism and induce the synthesis of several lipid intermediates, whose biological functions are still poorly understood. This work outlines the pivotal role of lipid metabolism in the heart and provides a lipocentric view of metabolic remodeling in heart failure. We will also critically revisit therapeutic attempts targeting cardiac lipid metabolism in heart failure and propose specific strategies for future investigations in this regard.