Decreased gallbladder response in leptin-deficient obese mice

Matthew I. Goldblatt, Deborah A. Swartz-Basile, Carol L. Svatek, Attila Nakeeb, Henry A. Pitt, K. Lillemoe, D. Dempsey, M. Dayton, Lawrence W. Way

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)438-444
Number of pages7
JournalJournal of Gastrointestinal Surgery
Volume6
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Obese Mice
Leptin
Gallbladder
Neuropeptide Y
Cholecystokinin
Acetylcholine
Obesity
Gallstones
Gallbladder Emptying
Hormones
Cholecystectomy
Baths
Adipocytes
Analysis of Variance
Students
Diet
Muscles
Incidence

Keywords

  • Acetylcholine
  • Cholecystokinin
  • Gallbladder motility
  • Leptin
  • Neuropeptide Y

ASJC Scopus subject areas

  • Surgery

Cite this

Goldblatt, M. I., Swartz-Basile, D. A., Svatek, C. L., Nakeeb, A., Pitt, H. A., Lillemoe, K., ... Way, L. W. (2002). Decreased gallbladder response in leptin-deficient obese mice. Journal of Gastrointestinal Surgery, 6(3), 438-444. https://doi.org/10.1016/S1091-255X(01)00046-4

Decreased gallbladder response in leptin-deficient obese mice. / Goldblatt, Matthew I.; Swartz-Basile, Deborah A.; Svatek, Carol L.; Nakeeb, Attila; Pitt, Henry A.; Lillemoe, K.; Dempsey, D.; Dayton, M.; Way, Lawrence W.

In: Journal of Gastrointestinal Surgery, Vol. 6, No. 3, 2002, p. 438-444.

Research output: Contribution to journalArticle

Goldblatt, MI, Swartz-Basile, DA, Svatek, CL, Nakeeb, A, Pitt, HA, Lillemoe, K, Dempsey, D, Dayton, M & Way, LW 2002, 'Decreased gallbladder response in leptin-deficient obese mice', Journal of Gastrointestinal Surgery, vol. 6, no. 3, pp. 438-444. https://doi.org/10.1016/S1091-255X(01)00046-4
Goldblatt, Matthew I. ; Swartz-Basile, Deborah A. ; Svatek, Carol L. ; Nakeeb, Attila ; Pitt, Henry A. ; Lillemoe, K. ; Dempsey, D. ; Dayton, M. ; Way, Lawrence W. / Decreased gallbladder response in leptin-deficient obese mice. In: Journal of Gastrointestinal Surgery. 2002 ; Vol. 6, No. 3. pp. 438-444.
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AU - Goldblatt, Matthew I.

AU - Swartz-Basile, Deborah A.

AU - Svatek, Carol L.

AU - Nakeeb, Attila

AU - Pitt, Henry A.

AU - Lillemoe, K.

AU - Dempsey, D.

AU - Dayton, M.

AU - Way, Lawrence W.

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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.

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KW - Cholecystokinin

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KW - Leptin

KW - Neuropeptide Y

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