The storage of fat within the heart muscle has been associated with reductions in force production, which has implications for the ability of the heart to adequately pump blood. With the assistance of membrane proteins known as transport proteins, fats from the blood can be moved into heart muscle cells, where they can either be stored or used for generating energy (within a structure called mitochondria) to pump blood. We provide evidence that in obese animals more fat accumulates within the heart as a result of their increased transport across the membranes of heart cells, not due to reductions in mitochondrial number or function. The knowledge of why fat accumulates in the heart may provide insight into novel treatments/therapies, and the current study suggests therapies focused on limiting the entry of fats into the heart may restore the ability of the heart to pump blood.
We aimed to determine whether an increased rate of long-chain fatty acid (LCFA) transport and/or a reduction in mitochondrial oxidation contributes to lipid deposition in hearts, as lipid accumulation within cardiac muscle has been associated with heart failure. In hearts of lean and obese Zucker rats we examined: (a) triacylglycerol (TAG) and mitochondrial content and distribution using transmission electron microscopy (TEM), (b) LCFA oxidation in cardiac myocytes, and in isolated subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria, and (c) rates of LCFA transport into cardiac vesicles. Compared to lean rats, in obese Zucker rats, lipid droplet size was similar but there were more (P < 0.05) droplets, and TAG esterification rates and contents were markedly increased. TEM analyses and biochemical determinations showed that SS and IMF mitochondria in obese animals did not appear to be different in their appearance, area, density and number, nor in citrate synthase, β-hydroxy-acyl-CoA dehydrogenase and carnitine palmitoyl-transferase-I enzymatic activities, electron transport chain proteins, nor in their rates of LCFA oxidation either in cardiac myocytes or in isolated SS and IMF mitochondria (P > 0.05). In contrast, sarcolemmal plasma membrane fatty acid binding protein (FABPpm) and fatty acid translocase (FAT/CD36) protein and palmitate transport rates into cardiac vesicles were increased (P < 0.05; +50%) in obese animals. Collectively these data indicate that mitochondrial dysfunction in LCFA oxidation is not responsible for lipid accumulation in obese Zucker rat hearts. Rather, increased sarcolemmal LCFA transport proteins and rates of LCFA transport result in a greater number of lipid droplets within cardiac muscle.