Differential leptin responses to acute and chronic biliary obstruction in rats

Background/Aims: Recently leptin, a protein released from adipocytes, has b een identified as a potent circulating satiety factor. We therefore underto ok this series of experiments to examine leptin's role in the anorexia asso ciated with biliary obstruction. Methods: Rats underwent either surgical bile duct resection (BDR) or sham r esection (sham). Body weight, and food and water intake were measured durin g 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 post-surgery, sham and BDR rats were sacrificed a nd sera collected for subsequent measurement of leptin hormone concentratio n by RIA. White adipose tissue was collected on days 2, 4, 6 and 8 for lept in mRNA determination by Northern blot. Results: Obstructive cholestasis in BDR rats caused significant anorexia fo r up to 7 days post-surgery, whereas in sham rats, a significant decrease i n 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 base-line levels by day 2 in both groups. Fat pad mass corrected to body weight was not sig nificantly different between the two experimental groups. Serum leptin leve ls 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 de creased 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 a norectic responses to centrally administered leptin. Conclusions: Leptin production is significantly increased early after bilia ry obstruction but is reduced after prolonged biliary obstruction. Increase d circulating leptin levels may contribute to the profound anorexia observe d early after biliary obstruction but appear not to mediate the anorexia ob served during more chronic biliary obstruction.