Whole body leptin kinetics and renal metabolism in vivo.

Leptin metabolism was investigated in male Sprague-Dawley rats by use of 125I-labeled leptin plasma kinetic and arteriovenous balance studies. When conscious rats received bolus venous injections of 125I-leptin, intact (precipitable) leptin quickly disappeared from circulation in a biexponential manner during the 2-h experimental period. After substantial delay, most of the injected radioactivity appeared in the urine. The data were described by a two-compartment model, which postulated that plasma leptin exchanged with a nonplasma pool and that all of the tracer cleared from plasma appeared in urine or in a degraded form in plasma. The half-life of leptin was 9.4 +/- 3.0 min, and the leptin production rate was 3.6 +/- 1.2 ng 100 g fat-1.min-1. The left kidney extracted 21 +/- 1.5% of intact arterial 125I-leptin 5 min after femoral venous injection. Endogenous arterial leptin was reduced 21 +/- 8 and 18 +/- 12%, respectively, in simultaneously sampled left and right renal veins. Renal elimination appears to be the major elimination mechanism for leptin in normal rats, and the kinetic studies suggest that uptake of leptin by renal tissue rather than glomerular filtration is the predominant elimination mechanism.