Diminished gallbladder motility in rotund leptin‐resistant obese mice

Abstract

BackgroundObesity is a risk factor for cholesterol gallstone formation, but the pathogenesis of this phenomenon remains unclear. Most human obesity is associated with diabetes and leptin‐resistance. Previous studies from this laboratory have demonstrated that diabetic leptin‐resistant (Lepdb) obese mice have low biliary cholesterol saturation indices, enlarged gallbladders and diminished gallbladder response to neurotransmitters. Recently, a novel leptin‐resistant mouse strain Leprdb‐rtnd (Rotund) has been discovered. Rotund mice are also obese, diabetic, and have an abnormal leptin receptor. Therefore, we tested the hypothesis that leptin‐resistant obese Rotund mice would have large gallbladders and reduced biliary motility. MethodsEight‐week‐old control (C57BL/6J, N=12) and Rotund leptin‐resistant (Leprdb‐rtnd, N=9) mice were fed a non‐lithogenic diet for four weeks. Animals were fasted and underwent cholecystectomy. Gallbladder volumes were recorded, and contractile responses (N/cm2) to acetylcholine (10−5 M), Neuropeptide Y (10−8,−7,−6 M), and cholecystokinin (10−10,−9,−8,−7 M) were measured. Results were analyzed using the Mann‐Whitney Rank Sum Test. ResultsCompared to control mice, Rotund mice had larger body weights, higher serum glucose levels, and greater gallbladder volumes (p<0.05). Rotund gallbladders had less contractility (p<0.05) to acetylcholine and cholecystokinin than control mice. Responses to Neuropeptide Y were also less, but not statistically significant, in the Rotund mice. ConclusionsThese data suggest that leptin‐resistant Rotund mice have (1) enlarged gallbladders with (2) diminished contractility compared to lean control mice. Therefore, this study confirms that leptin‐resistance is associated with abnormal biliary motility and may lead to gallstone formation in leptin‐resistant obesity.