Differential leptin responses to acute and chronic biliary obstruction in rats.

Background/aims: Recently leptin, a protein released from adipocytes, has been identified as a potent circulating satiety factor. We therefore undertook this series of experiments to examine leptin's role in the anorexia associated with biliary obstruction.
Methods: Rats underwent either surgical bile duct resection (BDR) or sham resection (sham). Body weight, and food and water intake were measured during a baseline period and for 8 days after surgery. At 4, 8 and 16 h as well as on days 2, 4, 6, and 8 postsurgery, sham and BDR rats were sacrificed and sera collected for subsequent measurement of leptin hormone concentration by RIA. White adipose tissue was collected on days 2, 4, 6 and 8 for leptin mRNA determination by Northern blot.
Results: Obstructive cholestasis in BDR rats caused significant anorexia for up to 7 days post-surgery, whereas in sham rats, a significant decrease in food intake was only observed in the first 24-h period following surgery. In both sham and BDR rats, water intake was significantly decreased during the first 24-h period after surgery, but had recovered to baseline levels by day 2 in both groups. Fat pad mass corrected to body weight was not significantly different between the two experimental groups. Serum leptin levels were significantly increased 4 and 8 h after surgery, had normalized by 16 h post-surgery, and were then decreased in BDR rats on days 2, 4, 6 and 8 compared with controls. Leptin mRNA levels in epididymal fat pads were decreased by approximately 2-fold in BDR rats compared with sham rats on days 2, 4, 6 and 8. Furthermore, day 5 BDR and sham rats demonstrated similar anorectic responses to centrally administered leptin.
Conclusions: Leptin production is significantly increased early after biliary obstruction but is reduced after prolonged biliary obstruction. Increased circulating leptin levels may contribute to the profound anorexia observed early after biliary obstruction but appear not to mediate the anorexia observed during more chronic biliary obstruction.