Figure 1: Overview of fatty acid and glucose oxidation in the heart

ACC, acetyl CoA carboxylase; AMPK, AMP- activated protein kinase; CPT, carnitine palmitoyl transferase; CAT, carnitine translocase; FACS, fatty acyl CoA synthetase; FAT, fatty acid transporter; GLUT, glucose transporter; LDH, lactate dehydrogenase; MCD, malonyl CoA decarboxylase; MPC, mitochondrial pyruvate carrier; PDH, pyruvate dehydrogenase; PDK, pyruvate dehydrogenase kinase; PDP, pyruvate dehydrogenase phosphatase; TCA, tricarboxylic acid; TG, triacylglycerol

Figure 2: Cardiac metabolic alterations in diabetes. In diabetes, strongly increased free fatty acid activate peroxisome proliferator-activated receptor a (PPARa), which up-regulates expression of genes involved in fatty acid (FA) oxidation. Increased FA oxidation shuts down glucose uptake and oxidation (insulin resistance), thereby blunts metabolic flexibility. Excessive FA are stored as triacylglycerol (TAG), which can mediate lipotoxicity. FA and reactive oxygen species (ROS) activate uncoupling protein 3 (UCP3), which makes ATP production less efficient

Figure 3: Mechanisms of cardioprotection of fatty acid oxidation inhibitors

Figure 4: Potential role of myoglobin in cardiac fatty acid metabolism. The heart is supplied with fatty acids (FA) derived from plasma FAs bound to albumin or incorporated in very-low-density lipoproteins (VLDL) triacylglycerols (TAG) or chylomicrons. The uptake occurs via diffusion or CD36/FATP transporters. Within the cytosol FAs are converted to FA acyl CoA by fatty acyl coA synthetases (FACS). The majority of FA acyl CoA is then channeled to carnitine palmitoyltransferase (CPT) system mediated by myoglobin (Mb). Converted to acylcarnitine by CPT1 FAs are translocated into the mitochondrial matrix, where they are converted back to fatty acyl CoA by CPT 2 to enter the β oxidation cycle. A minor portion of FA acyl CoA is converted to TAG under the control of Mb.