Gallbladder motility in agouti-yellow and leptin-resistant obese mice

Background. Obesity is a polygenic disorder that is associated with gallstone disease. We have previously shown that leptin deficiency in obese mice correlates with decreased gallbladder motility, suggesting that leptin plays a role in the link between gallstone disease and obesity. However, most obese humans are leptin-resistant, and relatively few are leptin-deficient. To confirm that leptin dysfunction is responsible for impaired gallbladder motility in obese mice, we hypothesized that leptin-resistant obese mice (Lep^db) would have abnormal gallbladder motility while obese mice with intact leptin function (Agouti Yellow, A^y) would have normal gallbladder motility. Materials and methods. Eighteen lean control (C57BL/6J), 10 A^y and 12 Lep^db female mice were fasted overnight, weighed, and livers and gallbladders were harvested. Liver weights and gallbladder volumes were measured. Gallbladder contractile responses (N/cm ²) to acetylcholine (10^-5M), neuropeptide Y (10 ^-8,-7,-6 M) and cholecystokinin (10^-10,-9,-8,-7M) were determined in muscle bath chambers. Results were analyzed by analysis of various (ANOVA) and with the Mann-Whitney Rank Sum Test. Results. Both Agouti yellow (A^y) and leptin-resistant (Lep^db) obese mice had body weights, liver weights and gallbladder volumes that were significantly greater (P < 0.01) than lean control mice. Leptin-resistant obese mice had gallbladder responses to acetylcholine, neuropeptide Y and cholecystokinin that were significantly less (P < 0.01) than both lean control and Agouti yellow obese mice. Conclusions. These data suggest that (1) leptin-resistant obese mice (Lep^db) have abnormal gallbladder motility and (2) obese mice with normal leptin metabolism (A^y) have normal gallbladder response to neurotransmitters. We conclude that leptin represents a link between obesity, gallbladder motility and gallstone formation.