The effect of centrally administered rat leptin on selection of 5 and 30% p
rotein diets was investigated in male Sprague-Dawley rats with indwelling i
.c.v. cannulas. Leptin (0 vs 2.5 mu g/day) was administered for 4 consecuti
ve days, followed by an 8-day withdrawal period. Total intake was reduced t
o approximately 50% of that in the vehicle injected group during each day f
ollowing leptin administration. Intake of both the 5 and 30% diets was redu
ced. Vehicle-treated rats selected a 13-15% CP diet. Diet selection in lept
in-treated rats was not different during the first day, but on Days 2-4, le
ptin-treated rats selected a 10% CP diet. Intake began to normalize within
24-48 h after the last treatment, and was not different by Day 3 of the wit
hdrawal period. Body weight was reduced by leptin treatment, and despite th
e normalization of food intake, did not recover during the withdrawal perio
d. Rats were sacrificed at the end of the 8-day withdrawal period. Despite
the reduction in body and carcass weights, liver, kidney, heart, and soleus
muscle weights were not different between control and leptin-treated group
s when expressed on an absolute or relative basis. However, epididymal and
retroperitoneal fat pad weights were still reduced 56 and 78%, respectively
, in rats that had been previously treated with leptin for 4 days and then
not treated for 8 days. In addition, circulating T-3 levels remained elevat
ed in rats that had been treated with leptin. Centrally administered leptin
has little effect on muscle mass, but had potent effects on intake of nono
bese rats and a sustained effect on adipose tissue mass, thyroid hormone st
atus, and body weight after withdrawal. Results from rats selecting between
diets varying in protein content suggest that leptin may cause avoidance o
f protein. (C) 1999 Elsevier Science Inc.