Elsevier

Surgery

Volume 136, Issue 2, August 2004, Pages 431-436
Surgery

Society of university surgeons
Gallbladder myocytes are short and cholecystokinin-resistant in obese diabetic mice

https://doi.org/10.1016/j.surg.2004.05.020Get rights and content

Abstract

Background

Obesity is associated with diabetes and gallstone formation. Obese leptin-deficient (Lepob) and leptin-resistant (Lepdb) mice are hyperglycemic and have enlarged gallbladders with diminished response in vitro to cholecystokinin (CCK) and acetylcholine (ACh). Whether this phenomenon is secondary to hyperosmolar myocytes and/or decreased neuromuscular transmission remains unclear. We hypothesize that myocytes from Lepob and Lepdb obese mice would not respond normally to neurotransmitters.

Methods

Cholecystectomy was performed on 39 lean, 19 Lepob, and 20 Lepdb 12-week-old female mice. The gallbladder was divided and enzymatically digested. Half of each gallbladder's myocytes had contraction induced by CCK (10−8 mol/L, n = 38) or ACh (10−5 mol/L, n = 40).

Results

Body weights, gallbladder volumes, and serum glucoses were greater for Lepob and Lepdb mice compared to controls (P < .001). Resting myocyte lengths from Lepob and Lepdb mice were 93% and 91% of the length of controls (P < .001). In response to CCK, lean myocytes shortened 6% (P < .01), while myocytes from obese mice demonstrated no shortening. None of the myocytes demonstrated significant shortening with ACh.

Conclusions

These data suggest that gallbladder myocytes from obese mice are (1) foreshortened and (2) have a diminished response to cholecystokinin. We conclude that altered leptin and/or increased glucose may foreshorten myocytes and decrease response to cholecystokinin.

Section snippets

Animals and diets

To study gallbladder myocyte contraction, we obtained 39 lean control C57bl/6J, 19 obese leptin-deficient Lepob, and 20 obese leptin-resistant Lepdb 7-week-old female mice from the Jackson Laboratory (Bar Harbor, Me). The mice were housed in cages of 5 mice each in a light (6am-6pm) and temperature (22°C) controlled environment for 5 weeks. All mice received standard, low-cholesterol chow diet (Ralston Purina, St. Louis, Mo) until 12 weeks of age. At 12 weeks of age, all animals were fasted

Body weight, gallbladder volume, and serum glucose data

Data for body weights, gallbladder volumes, and serum glucose are shown in Fig 2. The body weights of both the leptin-deficient Lepob and leptin-resistant Lepdb mice are greater than twice the size of the lean animals (42.9 and 41.7 vs 16.0 g, P < .001). Similarly, the gallbladder volumes of the obese animals (Lepob 36.2 μL, Lepdb 25.1 μL) were greater than the volumes of the lean animals (8.5 μL, P < .001). In addition, the serum glucose levels were dramatically higher in the obese animals

Discussion

In this study, leptin-deficient (Lepob) and leptin-resistant (Lepdb) obese mice fed a standard chow diet demonstrated significantly greater body weights and higher serum glucose, and had markedly enlarged gallbladders. The gallbladder myocytes from both the leptin-deficient and the leptin-resistant animals were significantly shorter than lean control myocytes. In addition, myocytes from obese animals demonstrated decreased contraction to stimulation by cholecystokinin at 10−8 mol/L

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    Presented at the 65th Annual Meeting of the Society of University Surgeons, St. Louis, Missouri, February 11-14, 2004.

    Supported by NIH grant R-01 DK44279.

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