Leptin is a hormone secreted by adipocytes, which plays an important role i
n the control of food intake and metabolic processes. In the current study,
a dose-dependent relationship was shown between a bolus intracerebroventri
cular rat recombinant leptin administration and reductions in food intake a
nd body weight in Sprague-Dawley rats. During the 24 h postinjection period
, food intake was decreased by 24, 26, and 52% with 0.625, 2.5, and 10 mu g
of leptin, respectively. Body weight was reduced by 2, 3, and 5% at 24 h a
fter leptin administration at the doses of 0.156, 2.5, and 10 mu g, respect
ively. Furthermore, indirect calorimetry demonstrated that five daily i.c.v
. injections of leptin resulted in an increase in heat production per unit
of metabolic body size and fat oxidation by approximately 10 and 48%, respe
ctively. In contrast, food-restricted rats that consumed the equivalent amo
unt of food as leptin-treated rats for 5 days decreased their energy expend
iture by 10%. Food restriction was found to decrease respiratory quotient i
n a similar pattern as the leptin administration. When ad lib feeding was r
esumed, food-restricted rats quickly recovered their normal food intakes, b
ody weights, and metabolism. Conversely, leptin treatment has prolonged eff
ects on body weight resulting from different metabolic responses than food
restriction. Leptin not only suppresses food intake, but also enhances ener
gy expenditure to reduce fat depots. (C) 1999 Elsevier Science Inc.