REMOVAL OF ENDOGENOUS LEPTIN FROM THE CIRCULATION BY THE KIDNEY

OBJECTIVE: This study was performed to test the hypothesis that the ki dneys play a primary role in the clearance of endogenous leptin from t he circulation of obese rats. DESIGN: Zucker (fa/fa) obese rats were a naesthetized and subjected to various surgical manipulations of the ki dneys. One hour after surgery arterial blood samples were taken at 1h intervals for times upto 8h. Plasma leptin concentrations were determi ned by radioimmunoassay. RESULTS: Bilateral nephrectomy induced a rapi d increase in plasma leptin concentrations above control values. In co ntrast, continuous intravenous re-injection of voided urine did not in crease circulating leptin concentrations, indicating that leptin is no t present in the urine in large quantities. This conclusion was confir med by the very low levels of detectable leptin in urine. Leptin is no t metabolized across the renal circulation and is extracted intact by the kidney. Simultaneous measurement of renal plasma flow established renal leptin extraction at approximately 59 ng/min for both kidneys. F ollowing intravenous infusion of leptin, renal clearance and whole bod y clearance were equal. This finding indicates that the kidneys alone are responsible for the systemic elimination of leptin in Zucker rats. Seven hours after bilateral ureteral ligation, a procedure which lowe rs glomerular filtration, plasma leptin concentrations were elevated. The renal extraction of leptin did not change over a wide range of pla sma leptin concentrations suggesting that renal leptin extraction is a high capacity, non-saturable process most probably glomerular filtrat ion. CONCLUSION: Endogenous leptin is rapidly cleared from the circula tion by the kidney by glomerular filtration followed by metabolic degr adation in the renal tubules.