Figure 1.

Overview of fatty acid metabolism in the heart. Exogenous fatty acids (FAs) are delivered to cardiomyocytes via albumin in the blood or hydrolyzed from triacylglycerols contained in very-low-density lipoproteins (VLDLs). FAs move across cell membranes through “flip-flop” passive translocation, as well as by active transport via FA translocase (FAT/CD36) and cytoplasmic fatty acid binding proteins (FABPs). FAs are converted to Acyl-CoA by the enzyme acyl-CoA synthetase-1 (ACSL1). Short- and medium-chain FAs can directly enter the mitochondria, while long-chain variants require the carnitine palmitoyltransferase system (CPT 1/2). Inside the mitochondria, fatty acyl-CoA undergoes β-oxidation to produce acetyl-CoA, which enters the tricarboxylic acid (TCA) cycle, flavin adenine dinucleotide (FADH₂), and nicotinamide adenine dinucleotide (NADH) to generate adenosine triphosphate (ATP). Free FAs also activate peroxisome proliferator-activated receptors (PPARs). PPARs, peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1), and estrogen-related receptors (ERRs) control the transcription of genes essential for FA transport and β-oxidation and lipid synthesis in the nucleus.