Gallbladder motility in agouti-yellow and leptin-resistant obese mice

Khoi Q. Tran, Deborah A. Swartz-Basile, Attila Nakeeb, Henry A. Pitt

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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 (Lepdb) would have abnormal gallbladder motility while obese mice with intact leptin function (Agouti Yellow, Ay) would have normal gallbladder motility. Materials and methods. Eighteen lean control (C57BL/6J), 10 Ay and 12 Lepdb 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 (10-5M), neuropeptide Y (10 -8,-7,-6 M) and cholecystokinin (10-10,-9,-8,-7M) 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 (Ay) and leptin-resistant (Lepdb) 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 (Lepdb) have abnormal gallbladder motility and (2) obese mice with normal leptin metabolism (Ay) have normal gallbladder response to neurotransmitters. We conclude that leptin represents a link between obesity, gallbladder motility and gallstone formation.

Original languageEnglish (US)
Pages (from-to)56-61
Number of pages6
JournalJournal of Surgical Research
Volume113
Issue number1
DOIs
StatePublished - Jul 2003
Externally publishedYes

Keywords

  • Acetylcholine
  • Agouti yellow
  • Cholecystokinin
  • Gallbladder disease
  • Gallbladder motility
  • Gallstone
  • Lep
  • Leptin
  • Neuropeptide Y
  • Obesity

ASJC Scopus subject areas

  • Surgery

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