The transport of fatty acids (FA) across membranes can be described by thre
e fundamental steps: adsorption, transmembrane movement, and desorption. In
model membranes, these steps are all rapid and spontaneous for most fatty
acids, suggesting that FA can enter cells by free diffusion rather than by
protein-mediated mechanisms. Here we present new fluorescence approaches th
at measure adsorption and transmembrane movement of FA independently. We sh
ow that FA adsorb to the plasma membrane of adipocytes and diffuse through
the membrane by the flip-flop mechanism within the time resolution of our m
easurements (similar to5 s). Thus we show that passive diffusion is a viabl
e mechanism, although we did not evaluate its exclusivity. Important implic
ations of the diffusion mechanism for neural cells are that all types of FA
could be available and that selectivity is controlled by metabolism. Studi
es of FA uptake into brain endothelial cells and other brain cell types nee
d to be performed to determine mechanisms of uptake, and metabolism of FA m
ust be separated in order to understand the role of membrane transport in t
he overall uptake process.