Cardiac fatty acid metabolism (FAO)

Cardiac fatty acid metabolism is the primary physiological process through which the heart generates ATP, providing approximately 60-90% of the energy required for myocardial contraction under healthy conditions (Lopaschuk et al., 2010). The process involves the uptake of long-chain fatty acids via transporters like CD36, their conversion into acyl-CoA, and their translocation into the mitochondria via the carnitine shuttle, a step regulated by carnitine palmitoyltransferase 1 (CPT1) (Stanley et al., 2005). In the mitochondria, these substrates undergo beta-oxidation to produce acetyl-CoA for the citric acid cycle. In pathological conditions such as heart failure or ischemia, excessive reliance on fatty acid oxidation can become maladaptive, increasing oxygen demand and inhibiting more efficient glucose utilization (Neubauer, 2007). Drugs like trimetazidine and perhexiline target components of this metabolic pathway to optimize cardiac energy use and protect the myocardium from ischemic damage by shifting substrate preference back toward glucose (Kantor et al., 2000). While this pathway encompasses several distinct molecular targets, its overall regulation is a critical therapeutic focus for metabolic cardiology.

Other names

Myocardial fatty acid oxidationCardiac fatty acid oxidationCardiac lipid metabolismMyocardial lipid metabolism

Pharmacological modulation of this pathway primarily involves the partial inhibition of fatty acid oxidation enzymes, such as 3-ketoacyl-CoA thiolase, or mitochondrial transport proteins like carnitine palmitoyltransferase 1 (CPT1), to promote a metabolic shift toward glucose oxidation, thereby improving myocardial oxygen efficiency and reducing lipotoxic injury (Lopaschuk et al., 2010; Stanley et al., 2005).