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Nonalcoholic fatty gallbladder disease: The influence of diet in lean and obese mice

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Journal of Gastrointestinal Surgery

Abstract

The obesity epidemic has contributed to an increased prevalence of gallstones and a higher percentage of chronic acalculous cholecystitis. Obesity is associated with Type II diabetes and hyperlipidemia in murine models. In addition, we have previously demonstrated that serum glucose, insulin, cholesterol, and triglycerides correlated with gallbladder contractility in murine models. However, the relative role of in sulin resistance and gallbladder fat infiltration in this phenomenon remain unclear. Therefore, we tested the hypothesis that gallbladder wall lipids are related to obesity and diet and are inversely correlated with gallbladder contractility. One hundred lean control (C7BL/6J) and 36 obese leptin-deficient (Lepob) 8-week-old female mice were fed either a chow diet or a 1.0% cholesterol, 15% butterfat (high-lipid) diet for four weeks. Pooled gallbladders were then analyzed for free fatty acids (FFA), phospholipids (PL), total cholesterol (TC), and triglycerides (TG). Cholesterol/phospholipid ratios were then calculated. The Lepob mice fed a chow diet had significantly higher (P<0.01) gallbladder lipids than the three other groups. The lean mice that were fed a high-lipid diet had increased (P<0.05) gallbladder TC compared to the lean mice on a chow diet. In addition, the cholesterol/phospholipid ratio was significantly in creased (P<0.01) in the lean mice fed a high-lipid diet compared to the other three groups. Finally, the high-lipid diet decreased gallbladder FFA (P<0.01), PL (P=0.08), and TC (P<0.05) in Lepob mice. These data suggest that (1) obese mice have increased gallbladder lipids; (2) a high-cholesterol, high-fat diet increases gallbladder lipids and the cholesterol/phospholipid ratio in lean mice; but (3) de creases gallbladder fatty acids, phospholipids, and cholesterol in obese mice. Prior studies have docu mented similarly decreased gallbladder response to neurotransmitters in obese mice on a chow diet, as well as lean and obese mice on a high-lipid diet. Therefore, we conclude that leptin-deficient obesity and/or a high-fat diet causes nonalcoholic fatty gallbladder disease, which is manifested by diminished gallbladder contractility.

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Authors and Affiliations

  1. Department of Surgery, The Ohio State University, Columbus, Ohio

    Matthew I. Goldblatt M.D.

  2. Department of Surgery, Indiana University School of Medicine, 535 Barnhill Drive, RT 130D, 46202, Indianapolis, IN

    Deborah A. Swartz-Basile Ph.D., Hayder H. Al-Azzawi M.D., Attila Nakeeb M.D. & Henry A. Pitt M.D.

  3. Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin

    Khoi Q. Tran M.D.

Authors
  1. Matthew I. Goldblatt M.D.
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  2. Deborah A. Swartz-Basile Ph.D.
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  3. Hayder H. Al-Azzawi M.D.
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  4. Khoi Q. Tran M.D.
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  5. Attila Nakeeb M.D.
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  6. Henry A. Pitt M.D.
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Correspondence to Henry A. Pitt M.D..

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Supported by NIH grant R-01 DK44279.

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Goldblatt, M.I., Swartz-Basile, D.A., Al-Azzawi, H.H. et al. Nonalcoholic fatty gallbladder disease: The influence of diet in lean and obese mice. J Gastrointest Surg 10, 193–201 (2006). https://doi.org/10.1016/j.gassur.2005.07.009

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  • DOI: https://doi.org/10.1016/j.gassur.2005.07.009

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