PLASMA LEPTIN CONCENTRATIONS ARE ONLY TRANSIENTLY INCREASED IN NEPHRECTOMIZED RATS

Leptin is an adipocyte-secreted hormone that has effects on appetite a nd energy expenditure. Several studies have shown that end-stage renal disease results in elevated plasma leptin concentrations and that the kidney is responsible for most of leptin elimination in rodents. Lept in metabolism was investigated in rats that underwent unilateral nephr ectomy to experimentally limit renal elimination function. Within 4 h of nephrectomy, plasma leptin concentrations increased from 2.9 +/- 0. 8 to 5.8 +/- 1.0 mu g/l but thereafter rapidly (<24 h) decreased to pr enephrectomy concentrations, despite continued elevated plasma creatin ine levels. Sham-operated rats maintained presurgical concentrations o f leptin and creatinine throughout the experiment. Kinetic studies of I-125-labeled leptin elimination showed that fractional catabolic rate s and half-lives of leptin in circulation were similar at 48 h in neph rectomized and sham-operated rats, suggesting that production of lepti n was unchanged after nephrectomy. Excretion of I-125 derived from lep tin in urine of nephrectomized rats was similar to that of sham-operat ed rats, and residual radioactivity was increased in the remaining kid neys excised from nephrectomized rats. These results demonstrate that I) leptin concentrations are quickly restored to presurgical levels in nephrectomized rats, and 2) it is leptin elimination, not leptin prod uction, that compensates to maintain leptin concentrations. Rapid meta bolic adaptation of remaining renal tissue may explain the restoration of normal leptin elimination in nephrectomized rats.