WHOLE-BODY LEPTIN KINETICS AND RENAL METABOLISM IN-VIVO

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