Leptin Ameliorates the Gallbladder's Response to Neurotransmitters in Congenitally Obese Mice
Abstracts
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Obesity is a known risk factor for gallstone formation; however, the pathogenesis of this phenomenon has not been clear. Leptin is a hormone produced by adipocytes which causes satiety through hypothalamic inhibition of neuropeptide Y (NPY) and cholecystokinin (CCK). We have previously demonstrated that leptin-deficient congenitally obese (Lepob) mice have increased gallbladder volume and decreased response to NPY and CCK. To confirm that these abnormalities were due to leptin, we tested the hypothesis that leptin administration would ameliorate the alterations in gallbladder motility observed in leptin-deficient obese mice. Twenty C57Bl/6J lean control female mice received daily injections of saline (n=9) or 5µg/g recombinant murine leptin IP (n=11). Eighteen Lepob obese female mice also received daily injections of saline (n=8) or 5µg/g leptin IP (n=10). All animals were weighed daily (g). After a month of injections, gallbladders (GB) were excised, bile volume (µl) was measured, and response in a muscle bath (N/cm2) to NPY (10-8,-7,-6M) and CCK (10-10,-9,-8,-7M) were measured. Results were analyzed by two-way ANOVA and least squares of means. These data suggest that leptin administration daily for one month 1) reduces body weight, 2) normalizes gallbladder volume and 3) ameliorates the gallbladder's response to neuropeptide Y and cholecystokinin. We conclude that leptin influences peripheral biliary as well as central hypothalamic neurotransmitters. Leptin deficiency causes gallbladder stasis which is corrected by leptin administration. Therefore, leptin represents a link between obesity and gallstone formation. |
