TY - JOUR
T1 - Decreased gallbladder response in leptin-deficient obese mice
AU - Goldblatt, Matthew I.
AU - Swartz-Basile, Deborah A.
AU - Svatek, Carol L.
AU - Nakeeb, Atilla
AU - Pitt, Henry A.
AU - Lillemoe, K.
AU - Dempsey, D.
AU - Dayton, M.
AU - Way, Lawrence W.
N1 - Funding Information:
Supported by grant RO1-DK44279-07 from the National Institutes of Health.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - Obesity is a major risk factor for gallstone formation, but the pathogenesis of this phenomenon remains unclear. Human data on gallbladder emptying are conflicting, and no animal data exist on the effect of obesity on gallbladder motility. Leptin, a hormone produced by adipocytes, is known to have central effects on neuropeptide Y and cholecystokinin, but the influence of leptin on the biliary effects of these hormones is unknown. Therefore we tested the hypothesis that leptin-deficient C57BL/6J-lepob obese mice would have decreased gallbladder responses to excitatory stimuli. Twelve-week-old lean control (C57BL/6J) (n = 22) and C57BL/6J-lepob obese (n = 20) female mice were fed a nonlithogenic diet. The mice were fasted overnight and underwent cholecystectomy. Whole gallbladders were placed in 3 ml muscle baths. After optimal length was determined with acetylcholine (10-5 mol/L, responses to increasing doses of neuropeptide Y (10-8 to 10 -6 mol/L) and cholecystokinin-8 (10-10 to 10-7 mol/L) were measured. Student's t test and two-way analysis of variance were used where appropriate. Results were expressed as Newtons per cross-sectional area. The lean control mice had significantly greater excitatory responses to acetylcholine than the obese mice (0.37 ± 0.05 vs. 0.16 ± 0.02, P < 0.01). The gallbladder responses were also greater when mice were treated with neuropeptide Y (10-8 mol/L: 0.00 ± 0.00 vs. 0.00 ± 0.00, NS; 10-7 mol/L: 0.12 ± 0.02 vs. 0.05 ± 0.01, P < 0.01; 10-6 mol/L: 0.26 ± 0.08 vs. 0.06 ± 0.01, P < 0.01) and cholecystokinin (10-10 mol/L: 0.27 ± 0.04 vs. 0.13 ± 0.02, P < 0.01; 10-9 mol/L: 0.59 ± 0.08 vs. 0.27 ± 0.04, P < 0.01; 10-8 mol/L: 0.80 ± 0.11 vs. 0.37 ± 0.05, P < 0.01; 10-7 mol/L: 0.86 ± 0.11 vs. 0.44 ± 0.06, P < 0.01). These data suggest that genetically obese, leptin-deficient mice have decreased responses to acetylcholine, neuropeptide Y, and cholecystokinin. We conclude that decreased gallbladder motility contributes to the increased incidence of gallstones associated with obesity.
AB - Obesity is a major risk factor for gallstone formation, but the pathogenesis of this phenomenon remains unclear. Human data on gallbladder emptying are conflicting, and no animal data exist on the effect of obesity on gallbladder motility. Leptin, a hormone produced by adipocytes, is known to have central effects on neuropeptide Y and cholecystokinin, but the influence of leptin on the biliary effects of these hormones is unknown. Therefore we tested the hypothesis that leptin-deficient C57BL/6J-lepob obese mice would have decreased gallbladder responses to excitatory stimuli. Twelve-week-old lean control (C57BL/6J) (n = 22) and C57BL/6J-lepob obese (n = 20) female mice were fed a nonlithogenic diet. The mice were fasted overnight and underwent cholecystectomy. Whole gallbladders were placed in 3 ml muscle baths. After optimal length was determined with acetylcholine (10-5 mol/L, responses to increasing doses of neuropeptide Y (10-8 to 10 -6 mol/L) and cholecystokinin-8 (10-10 to 10-7 mol/L) were measured. Student's t test and two-way analysis of variance were used where appropriate. Results were expressed as Newtons per cross-sectional area. The lean control mice had significantly greater excitatory responses to acetylcholine than the obese mice (0.37 ± 0.05 vs. 0.16 ± 0.02, P < 0.01). The gallbladder responses were also greater when mice were treated with neuropeptide Y (10-8 mol/L: 0.00 ± 0.00 vs. 0.00 ± 0.00, NS; 10-7 mol/L: 0.12 ± 0.02 vs. 0.05 ± 0.01, P < 0.01; 10-6 mol/L: 0.26 ± 0.08 vs. 0.06 ± 0.01, P < 0.01) and cholecystokinin (10-10 mol/L: 0.27 ± 0.04 vs. 0.13 ± 0.02, P < 0.01; 10-9 mol/L: 0.59 ± 0.08 vs. 0.27 ± 0.04, P < 0.01; 10-8 mol/L: 0.80 ± 0.11 vs. 0.37 ± 0.05, P < 0.01; 10-7 mol/L: 0.86 ± 0.11 vs. 0.44 ± 0.06, P < 0.01). These data suggest that genetically obese, leptin-deficient mice have decreased responses to acetylcholine, neuropeptide Y, and cholecystokinin. We conclude that decreased gallbladder motility contributes to the increased incidence of gallstones associated with obesity.
KW - Acetylcholine
KW - Cholecystokinin
KW - Gallbladder motility
KW - Leptin
KW - Neuropeptide Y
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U2 - 10.1016/S1091-255X(01)00046-4
DO - 10.1016/S1091-255X(01)00046-4
M3 - Article
C2 - 12022998
AN - SCOPUS:15944425316
VL - 6
SP - 438
EP - 444
JO - Journal of Gastrointestinal Surgery
JF - Journal of Gastrointestinal Surgery
SN - 1091-255X
IS - 3
ER -