PET Measurements of Organ Metabolism: The Devil Is in the Details

Abnormalities in myocardial fatty acid (FA) metabolism, which are primarily driven by an increase in plasma FAs delivered to the heart, play a central role in the pathogenesis of the cardiomyopathic processes associated with obesity, insulin resistance, and diabetes (1). Moreover, the prevalence and magnitude of the cardiovascular complications of these diseases, such as left ventricular hypertrophy, heart failure, and ischemic heart disease, are typically more pronounced in women compared with men (2,3). Thus, it is tempting to speculate that the sex differences in myocardial FA metabolism may be contributory to this interaction. Evidence to support this notion has come from studies using positron emission tomography (PET), which because of its inherent quantitative capabilities and diversity of metabolic radiotracers is the most commonly used imaging method to measure organ metabolism. PET studies using the FA radiotracer 1-11C-palmitate have recently shown that myocardial FA uptake and oxidation are higher in obese women compared with men and that this sex disparity appears to become more pronounced when one transitions to obesity with concurrent type 2 diabetes (4,5). However, myocardial FA metabolism is dependent on the plasma delivery of FA from nonesterified FA (NEFA) bound to albumin as well as those incorporated into triglyceride (TG), either as chylomicrons (CM-TG) or VLDLs (VLDL-TG). Fatty acids bound to TGs are made available to the myocardium via their release by lipoprotein lipase located on the capillary endothelium. Measuring this contribution of TG-extracted FAs destined for metabolism is important because it represents a major source of FAs from dietary intake (DFA) and evidence suggesting that the source of extracted FAs may impact their metabolic fate in tissue (6,7). To date, the PET method described above to measure myocardial FA metabolism relies on intravenous administration of FA radiotracers and …