Evaluation of free fatty acid metabolism in vivo.

In order to enable detailed studies of free fatty acid (FFA) metabolism, we recently introduced a method for the evaluation of tissue-specific FFA metabolism in vivo. The method is based on the simultaneous use of C-14-palmitate (C-14-P) and the non-beta-oxidizable FFA analogue, [9,10-H-3]-(R)-2-bromopalmitate (H-3-R-BrP). Indices of total FFA utilization and incorporation into storage products are obtained from tissue concentrations of H-3 and C-14, respectively, following intravenous administration of H-3-R-BrP and C-14-P and their disappearance from plasma into tissues. This review covers the basis for, and developments in, the methodology, as well as some of the applications to date. In the rat, the method has been used to characterize tissue-specific alterations in FFA metabolism in various situations, including skeletal muscle contraction, fasting, hyperinsulinemia, and various pharmacological manipulations. The results of all these studies clearly demonstrate tissue-level control of FFA utilization and metabolic fate, refuting the traditional view that FFA utilization is simply supply-driven. Recent developments enable the simultaneous evaluation of both tissue-specific FFA and glucose metabolism by integrating the use of 2-deoxyglucose and stable isotope-labeled glucose tracers. In conclusion, the H-3-R-BrP methodology, especially in combination with other tracers, represents a powerful tool for elucidation of tissue-specific fatty acid metabolism in vivo.