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Medical Science Monitor Basic Research


eISSN: 1643-3750

Human leptin administered intraperitoneally stimulates natriuresis and decreasesrenal medullary Na+, K+-ATPase activity in the rat - impaired effect in dietary-induced obesity.

Grazyna W jcicka, Jerzy Bełtowski, Dionizy Górny, Andrzej Marciniak

Med Sci Monit 2002; 8(6): BR221-229

ID: 420820

Available online:

Published: 2002-06-18

BACKGROUND: Leptin, produced by adipose tissue, apart from regulating foodintake and energy expenditure, also has natriuretic activity. In this study we examined the effect ofleptin on renal Na+, K+-ATPase responsible for active tubular sodium reabsorption, and compared the renaleffects of leptin in lean and obese rats.MATERIAL/METHODS: Male Wistar rats were either kept on normallaboratory chow or made obese by a high-calorie diet. The animals were placed in metabolic cages andurine was collected in 2-hour periods.RESULTS: In lean animals, leptin (1 mg/kg i.p.) caused a 139.5%increase in urine output, a 112.4% increase in natriuresis, and a 57.2% increase in the fractional excretionof sodium, but had no effect on the glomerular filtration rate. Leptin at this dose decreased renal medullaryNa+, K+-ATPase activity at 30 minutes, 1 hour and 2 hours by 31%, 34.3% and 21.2%, respectively. Theeffect of leptin on Na+, K+-ATPase at 1 hour was dose-dependent; the lowest dose inducing significantinhibition was 0.25 mg/kg. By contrast, leptin had no effect on either cortical Na+, K+-ATPase or theouabain-resistant fraction of ATPase. In obese rats, leptin increased urine output by only 29.1% andnatriuresis by 28.9%, and had no significant effect on medullary Na+, K+-ATPase.CONCLUSIONS: Leptin stimulatesnatriuresis primarily by inhibiting tubular sodium reabsorption. This effect is mediated, at least partially,by decreased Na+, K+-ATPase activity in the renal medulla, and is impaired in obese rats.

Keywords: Animals, Blood Pressure, Diet, Injections, Intraperitoneal, Kidney Medulla, Leptin, Na(+)-K(+)-Exchanging ATPase, Natriuresis, Obesity, Rats, Rats, Wistar, Research Support, Non-U.S. Gov