Validation of the [1,2-C-13]acetate recovery factor for correction of [U-C-13]palmitate oxidation rates in humans

1. The validity of estimations of plasma fatty acid oxidation using tracers has often been questioned. The appearance of isotopic markers in breath CO 2 is delayed and incomplete. Recently suggestions have been made that subst antial amounts of tracer are incorporated into products of the tricarboxyli c acid cycle (e.g, glucose, glutamine and glutamate) and that an acetate co rrection factor can be used to correct for tracer fixation. In the present study we investigated whether the appearance of (CO2)-C-13 during a separat e infusion of [1,2-C-13] acetate could be used for correction of [U-C-13]pa lmitate oxidation rates in studies lasting <2 h and we quantified the appea rance of tracer in the glutamine, glutamate and glucose pools of the body. 2. An infusion of either [1,2-C-13]acetate (0.104 mu mol min(-1) kg(-1)) or [U-C-13]palmitate (0.013 mu mol min(-1) kg(-1)) was given to eight male su bjects and continued for 2 h at rest. In six subjects the infusion of [1,2- C-13]acetate was repeated to determine reproducibility of the acetate recov ery. 3. Fractional recovery in breath from [1,2-13C]acetate gradually increased during the infusion period at rest from 14.1 +/- 0.6% at 60 min to 26.5 +/- 0.5% at 120 min after the start of the infusion. Intersubject coefficient of variance was 8.3 +/- 0.6% and intrasubject coefficient of variance of th e acetate recovery tests was 4.0 +/- 1.5 %. After 2 h of [1,2-C-13]acetate infusion, 12.4 +/- 0.8 and 10.3 +/- 0.9 % of infused C-13 was incorporated in the glutamine and glutamate pools, respectively. 4. In conclusion, the [1,2-C-13]acetate recovery factor can be used for cor recting the rate of [U-C-13]palmitate oxidation in infusing studies of 2 h in resting conditions. Failure to use this recovery factor leads to a subst antial underestimation of the rate of plasma free fatty acid oxidation. The extent of label fixation could largely be explained by accumulation of tra cer carbon in glutamine and glutamate, and the accumulation in glucose is n egligible.