Diminished gallbladder motility in rotund leptin-resistant obese mice

Shannon J. Graewin, Khoi Q. Tran, Jurgen K. Naggert, Kuen Ho Lee, Debbie Swartz-Basile, Attila Nakeeb, Henry A. Pitt

Research output: Contribution to journalArticle

Abstract

Background. Obesity is a risk factor for cholesterol gallstone formation, but the pathogenesis of this phenomenon remains unclear. Most human obesity is associated with diabetes and leptin-resistance. Previous studies from this laboratory have demonstrated that diabetic leptin-resistant (Lepdb) obese mice have low biliary cholesterol saturation indices, enlarged gallbladders and diminished gallbladder response to neurotransmitters. Recently, a novel leptin-resistant mouse strain Leprdb-rtnd (Rotund) has been discovered. Rotund mice are also obese, diabetic, and have an abnormal leptin receptor. Therefore, we tested the hypothesis that leptin-resistant obese Rotund mice would have large gallbladders and reduced biliary motility. Methods. Eight-week-old control (C57BL/6J, N = 12) and Rotund leptin-resistant (Leprdb-rtnd N= 9) mice were fed a non-lithogenic diet for four weeks. Animals were fasted and underwent cholecystectomy. Gallbladder volumes were recorded, and contractile responses (N/cm2) to acetylcholine (10-5 M), Neuropeptide Y (10-8,-7,-6 M), and cholecystokinin (10-10,-9,-8,,-7 M) were measured. Results were analyzed using the Mann-Whitney Rank Sum Test. Results. Compared to control mice, Rotund mice had larger body weights, higher serum glucose levels, and greater gallbladder volumes (p <0.05). Rotund gallbladders had less contractility (p <0.05) to acetylcholine and cholecystokinin than control mice. Responses to Neuropeptide Y were also less, but not statistically significant, in the Rotund mice. Conclusions. These data suggest that leptin-resistant Rotund mice have (1) enlarged gallbladders with (2) diminished contractility compared to lean control mice. Therefore, this study confirms that leptin-resistance is associated with abnormal biliary motility and may lead to gallstone formation in leptin-resistant obesity.

Original languageEnglish (US)
Pages (from-to)139-143
Number of pages5
JournalHPB
Volume7
Issue number2
DOIs
StatePublished - 2005
Externally publishedYes

Fingerprint

Obese Mice
Leptin
Gallbladder
Obesity
Neuropeptide Y
Cholecystokinin
Gallstones
Acetylcholine
Cholesterol
Leptin Receptors
Cholecystectomy
Nonparametric Statistics
Neurotransmitter Agents
Body Weight
Diet
Glucose

Keywords

  • Cholesterol
  • Diabetes mellitus
  • Gallbladder
  • Gallstones
  • Motility

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Graewin, S. J., Tran, K. Q., Naggert, J. K., Lee, K. H., Swartz-Basile, D., Nakeeb, A., & Pitt, H. A. (2005). Diminished gallbladder motility in rotund leptin-resistant obese mice. HPB, 7(2), 139-143. https://doi.org/10.1080/13651820510028800

Diminished gallbladder motility in rotund leptin-resistant obese mice. / Graewin, Shannon J.; Tran, Khoi Q.; Naggert, Jurgen K.; Lee, Kuen Ho; Swartz-Basile, Debbie; Nakeeb, Attila; Pitt, Henry A.

In: HPB, Vol. 7, No. 2, 2005, p. 139-143.

Research output: Contribution to journalArticle

Graewin, SJ, Tran, KQ, Naggert, JK, Lee, KH, Swartz-Basile, D, Nakeeb, A & Pitt, HA 2005, 'Diminished gallbladder motility in rotund leptin-resistant obese mice', HPB, vol. 7, no. 2, pp. 139-143. https://doi.org/10.1080/13651820510028800
Graewin SJ, Tran KQ, Naggert JK, Lee KH, Swartz-Basile D, Nakeeb A et al. Diminished gallbladder motility in rotund leptin-resistant obese mice. HPB. 2005;7(2):139-143. https://doi.org/10.1080/13651820510028800
Graewin, Shannon J. ; Tran, Khoi Q. ; Naggert, Jurgen K. ; Lee, Kuen Ho ; Swartz-Basile, Debbie ; Nakeeb, Attila ; Pitt, Henry A. / Diminished gallbladder motility in rotund leptin-resistant obese mice. In: HPB. 2005 ; Vol. 7, No. 2. pp. 139-143.
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abstract = "Background. Obesity is a risk factor for cholesterol gallstone formation, but the pathogenesis of this phenomenon remains unclear. Most human obesity is associated with diabetes and leptin-resistance. Previous studies from this laboratory have demonstrated that diabetic leptin-resistant (Lepdb) obese mice have low biliary cholesterol saturation indices, enlarged gallbladders and diminished gallbladder response to neurotransmitters. Recently, a novel leptin-resistant mouse strain Leprdb-rtnd (Rotund) has been discovered. Rotund mice are also obese, diabetic, and have an abnormal leptin receptor. Therefore, we tested the hypothesis that leptin-resistant obese Rotund mice would have large gallbladders and reduced biliary motility. Methods. Eight-week-old control (C57BL/6J, N = 12) and Rotund leptin-resistant (Leprdb-rtnd N= 9) mice were fed a non-lithogenic diet for four weeks. Animals were fasted and underwent cholecystectomy. Gallbladder volumes were recorded, and contractile responses (N/cm2) to acetylcholine (10-5 M), Neuropeptide Y (10-8,-7,-6 M), and cholecystokinin (10-10,-9,-8,,-7 M) were measured. Results were analyzed using the Mann-Whitney Rank Sum Test. Results. Compared to control mice, Rotund mice had larger body weights, higher serum glucose levels, and greater gallbladder volumes (p <0.05). Rotund gallbladders had less contractility (p <0.05) to acetylcholine and cholecystokinin than control mice. Responses to Neuropeptide Y were also less, but not statistically significant, in the Rotund mice. Conclusions. These data suggest that leptin-resistant Rotund mice have (1) enlarged gallbladders with (2) diminished contractility compared to lean control mice. Therefore, this study confirms that leptin-resistance is associated with abnormal biliary motility and may lead to gallstone formation in leptin-resistant obesity.",
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AU - Swartz-Basile, Debbie

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N2 - Background. Obesity is a risk factor for cholesterol gallstone formation, but the pathogenesis of this phenomenon remains unclear. Most human obesity is associated with diabetes and leptin-resistance. Previous studies from this laboratory have demonstrated that diabetic leptin-resistant (Lepdb) obese mice have low biliary cholesterol saturation indices, enlarged gallbladders and diminished gallbladder response to neurotransmitters. Recently, a novel leptin-resistant mouse strain Leprdb-rtnd (Rotund) has been discovered. Rotund mice are also obese, diabetic, and have an abnormal leptin receptor. Therefore, we tested the hypothesis that leptin-resistant obese Rotund mice would have large gallbladders and reduced biliary motility. Methods. Eight-week-old control (C57BL/6J, N = 12) and Rotund leptin-resistant (Leprdb-rtnd N= 9) mice were fed a non-lithogenic diet for four weeks. Animals were fasted and underwent cholecystectomy. Gallbladder volumes were recorded, and contractile responses (N/cm2) to acetylcholine (10-5 M), Neuropeptide Y (10-8,-7,-6 M), and cholecystokinin (10-10,-9,-8,,-7 M) were measured. Results were analyzed using the Mann-Whitney Rank Sum Test. Results. Compared to control mice, Rotund mice had larger body weights, higher serum glucose levels, and greater gallbladder volumes (p <0.05). Rotund gallbladders had less contractility (p <0.05) to acetylcholine and cholecystokinin than control mice. Responses to Neuropeptide Y were also less, but not statistically significant, in the Rotund mice. Conclusions. These data suggest that leptin-resistant Rotund mice have (1) enlarged gallbladders with (2) diminished contractility compared to lean control mice. Therefore, this study confirms that leptin-resistance is associated with abnormal biliary motility and may lead to gallstone formation in leptin-resistant obesity.

AB - Background. Obesity is a risk factor for cholesterol gallstone formation, but the pathogenesis of this phenomenon remains unclear. Most human obesity is associated with diabetes and leptin-resistance. Previous studies from this laboratory have demonstrated that diabetic leptin-resistant (Lepdb) obese mice have low biliary cholesterol saturation indices, enlarged gallbladders and diminished gallbladder response to neurotransmitters. Recently, a novel leptin-resistant mouse strain Leprdb-rtnd (Rotund) has been discovered. Rotund mice are also obese, diabetic, and have an abnormal leptin receptor. Therefore, we tested the hypothesis that leptin-resistant obese Rotund mice would have large gallbladders and reduced biliary motility. Methods. Eight-week-old control (C57BL/6J, N = 12) and Rotund leptin-resistant (Leprdb-rtnd N= 9) mice were fed a non-lithogenic diet for four weeks. Animals were fasted and underwent cholecystectomy. Gallbladder volumes were recorded, and contractile responses (N/cm2) to acetylcholine (10-5 M), Neuropeptide Y (10-8,-7,-6 M), and cholecystokinin (10-10,-9,-8,,-7 M) were measured. Results were analyzed using the Mann-Whitney Rank Sum Test. Results. Compared to control mice, Rotund mice had larger body weights, higher serum glucose levels, and greater gallbladder volumes (p <0.05). Rotund gallbladders had less contractility (p <0.05) to acetylcholine and cholecystokinin than control mice. Responses to Neuropeptide Y were also less, but not statistically significant, in the Rotund mice. Conclusions. These data suggest that leptin-resistant Rotund mice have (1) enlarged gallbladders with (2) diminished contractility compared to lean control mice. Therefore, this study confirms that leptin-resistance is associated with abnormal biliary motility and may lead to gallstone formation in leptin-resistant obesity.

KW - Cholesterol

KW - Diabetes mellitus

KW - Gallbladder

KW - Gallstones

KW - Motility

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