Validation of a new method for determination of free fatty acid turnover

The accuracy of tracer methods for estimating free fatty acid (FFA) rate of appearance (R(a)), either under steady-state conditions or under non-steady-state conditions, has not been previously investigated. In the present study, endogenous lipolysis (traced with ¹⁴C palmitate) was suppressed in six mongrel dogs with a high-carbohydrate meal 10 h before the experiment, together with infusions of glucose, propranolol, and nicotinic acid during the experimental period. Both steady-state and non-steady-state equations were used to determine oleate R(a) ([³H]oleate) before, during and after a stepwise infusion of an oleic acid emulsion. Palmitate R(a) did not change during the experiment. Steady-state equations gave the best estimates of oleate inflow ~93% of the known oleate infusion rate overall, while errors in tracer estimates of inflow were obtained when non-steady-state equations were used. The metabolic clearance rate of oleate was inversely related to plasma concentration (P<0.01). In conclusion, accurate estimates of FFA inflow were obtained when steady-state equations were used, even under conditions of abrupt and recent changes in R(a). Non-steady-state equations, in contrast, may provide erroneous estimates of inflow. The decrease in metabolic clearance rate during exogenous infusion of oleate suggests that FFA transport may follow second-order kinetics.