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.


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(-5)M), neuropeptide Y (10(-8,-7,-6) M) and cholecystokinin (10(-10,-9,-8,-7)M) 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.
Tran
Khoi Q
KQ
Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Swartz-Basile
Deborah A
DA
Nakeeb
Attila
A
Pitt
Henry A
HA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology; D005260:Female; D016473:Gallbladder Emptying / Q000187:drug effects / Q000502:physiology*; D020738:Leptin / Q000378:metabolism*; D051379:Mice; D008820:Mice, Obese; D009478:Neuropeptide Y / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009765:Obesity / Q000503:physiopathology*
D020738:Leptin; D009478:Neuropeptide Y; D018377:Neurotransmitter Agents; D002766:Cholecystokinin; D000109:Acetylcholine