Measurement of free fatty acid kinetics during non-equilibrium tracer conditions in man: implications for the estimation of the rate of appearance of free fatty acids.
BACKGROUND
This study aimed to document the applicability and variability of free fatty acid (FFA) kinetic parameters during non-equilibrium and equilibrium tracer conditions in man.


METHODS
FFA kinetic parameters were assessed after an overnight fast in six healthy non-obese and three obese subjects as well as in three patients with non-insulin-dependent diabetes mellitus (NIDDM) by infusion of [14C]-palmitate of 60 min (study A) and 10 min duration (study B).


RESULTS
The kinetic parameters estimated from the upstroke and downstroke of the plasma FFA specific activity curve (non-equilibrium) were not statistically different within studies A and B. Furthermore, there were no significant differences in any of the FFA kinetic parameters between studies A and B. The averaged plasma levels of FFA obtained during the up- and downstroke from studies A and B were higher in obese subjects and NIDDM patients than in non-obese subjects (P < 0.01). The averaged total rate of appearance (TRa) of FFA was higher in obese subjects than in non-obese subjects (P < 0.02). The TRa and metabolic clearance rate (MCR), estimated from non-equilibrium conditions, were about 25% higher than the apparent values obtained from steady-state measurement in all subjects combined (P < 0.01), suggesting considerable recirculation of label from hydrolysis of labelled esterified fatty acids. Indeed, in three non-obese subjects, the radiolabel in esterified fatty acids was approximately 50% of labelled FFA at 60 min of label infusion. The coefficients of variation of the kinetic parameters were consistently larger in study A than in study B.


CONCLUSIONS
FFA kinetic parameters can be estimated with sufficient precision using non-equilibrium data from short-term labelled palmitate infusion. Short-term label infusion has the advantage that label recirculation is prevented and exposure to radiation is limited.
Riemens
S C
SC
University Hospital Groningen, The Netherlands.
Dullaart
R P
RP
Franssen
E J
EJ
Piers
D A
DA
Reitsma
W D
WD
Sluiter
W J
WJ
D000328:Adult; D000368:Aged; D002250:Carbon Radioisotopes; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D019308:Palmitic Acid / Q000493:pharmacokinetics; D011849:Radioactive Tracers; D015203:Reproducibility of Results; D013997:Time Factors
D002250:Carbon Radioisotopes; D005230:Fatty Acids, Nonesterified; D011849:Radioactive Tracers; D019308:Palmitic Acid