QS270. Leptin Blocks Gallbladder Absorption but Not Secretion

Introduction: The gallbladder has both absorptive and secretory functions, and alterations in these functions are significant contributing factors in gallstone pathogenesis. We have recently demonstrated that obese, leptin deficient (Lep ob) mice have enlarged gallbladder volumes and decreased gallbladder contractility and that leptin regulates gallbladder genes related to absorption and secretion. In addition, we have shown that hyperleptinemic (Lep db) mice have resting gallbladder secretion rather than gallbladder absorption found in leptin-deficient (Lep ob) and lean control mice. However, the effect of leptin on gallbladder fluid transport remains unclear. Therefore, we sought to determine whether exogenous leptin administration would alter fluid flux across the gallbladder epithelium. Methods: Eight week old lean, (C57BL/6J, n=18), obese leptin-deficient (Lep Ob, n=14) and obese leptin-resistant (Lep Db, n=13) female mice were fed a 25% fat diet for four weeks. At 12 weeks of age, the mice were fasted overnight, anesthetized and underwent laparotomy. The gallbladders were cannulated in vivo with a PE10 (0.61 mm) polyethylene tube and inflated with Krebs buffer to a pressure of 15mmHg. The gallbladder was then excised and suspended in a bath containing oxygenated Krebs buffer (37°C) for 1 hour and weighed at 10 minute intervals. Recombinant murine leptin was added to the bath (6ng/mL) of 5 lean, 4 Lep Ob and 5 Lep Db gallbladders. The gallbladders were then opened longitudinally and placed on a grid to determine and control for surface area. Data were analyzed by Anova and Tukey testing. Results: Results for weight change are presented in the table. Conclusions: These data suggest that 1) leptin blocks absorption in the lean C57Bl/6J and obese Lep ob mice, and 2) leptin has no effect on absorption or secretion in Lep Db mice. Therefore, we conclude that leptin influences gallbladder absorption but not secretion. Tabled 1 % Baseline Weight % Baseline Weight % Baseline Weight % Baseline Weight 0–30 min 0–30 min 30–60 min 30–60 min Vehicle Leptin Vehicle Leptin C57BI/6J 94.8 ± 0.5 100.0 ± 0.7 ⁎ p<0.05 vs vehicle. 88.2 ± 0.7 98.7 ± 1.1 ⁎ p<0.05 vs vehicle. Lep Ob 96.6 ± 0.5 † p<0.05 vs other strains. 99.3 ± 0.8 ⁎ p<0.05 vs vehicle. 92.7 ± 0.8 † p<0.05 vs other strains. 96.9 ± 1.2 ⁎ p<0.05 vs vehicle. Lep Db 102.2 ± 0.5 † p<0.05 vs other strains. 101.9 ± 0.7 98.5 ± 0.9 † p<0.05 vs other strains. 98.9 ± 1.1 p<0.05 vs vehicle. † p<0.05 vs other strains. Open table in a new tab