Seeing Is Believing: Dietary Fatty Acids Hurry Up From the Stomach to the Heart of Patients With Impaired Glucose Tolerance
- Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy
- Corresponding author: Patricia Iozzo, .
Cardiovascular disease and heart failure are leading complications in patients with type 2 diabetes, prediabetes, and obesity in whom circulating fatty acid (FA) levels are commonly elevated. Abnormalities in FA handling in skeletal muscle, liver, and adipose tissue may initiate or perpetuate a cycle of insulin resistance, impaired glucose utilization, and dyslipidemia, thereby leading to substrate overflow to the heart. From animal studies, we learn that once an excess of FA is forced to enter myocardial cells, lipotoxicity and functional loss occur (1–4). However, less is known about the organ-specific fate of endogenous or ingested lipids in humans. This is because systemic fluxes of nonesterified fatty acids (NEFAs) and triglycerides (TGs) cannot be extrapolated to individual organs because local mechanisms such as perfusion, lipolysis, oxygen availability, and inward transport may intervene in the response of individual tissues to the oversupply of FAs. In this issue of Diabetes, Labbé et al. (5) report on the use of positron emission tomography (PET) to image the organ-specific fate of ingested FAs, including chylomicron-derived FA in the myocardium, adipose tissue, skeletal muscle, and liver in subjects with impaired glucose tolerance (IGT) and normal glucose tolerance.
PET is a nuclear imaging technique that uses short-lived positron-emitting radioisotopes (e.g., 18F, 11C) to label molecules of interest (e.g., substrates) and visualize their fate in individual organs. Native substrates, such as 11C-labeled glucose or long-chain FAs have a complex fate in tissue because they enter many metabolic pathways and part of the label is washed-out during oxidation or substrate output. Their labeled analogs 18F-2-fluoro-2-deoxyglucose (18F-FDG) and 14(R,S)-18F-fluoro-6-thia-heptadecanoic acid (18F-FTHA) cannot, or can only partially go through oxidative catabolism. Therefore, they become trapped in …