Nonalcoholic Fatty gallbladder disease: the influence of diet in lean and obese mice. J Gastrointest Surg 2006 Feb;10(2):193-201
Date
02/04/2006Pubmed ID
16455450DOI
10.1016/j.gassur.2005.07.009Scopus ID
2-s2.0-29744458138 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
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 insulin 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 (Lep(ob)) 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 Lep(ob) 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 increased (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 Lep(ob) 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) decreases gallbladder fatty acids, phospholipids, and cholesterol in obese mice. Prior studies have documented 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.
Author List
Goldblatt MI, Swartz-Basile DA, Al-Azzawi HH, Tran KQ, Nakeeb A, Pitt HAAuthor
Matthew I. Goldblatt MD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adipose TissueAnimals
Butter
Cholesterol
Cholesterol, Dietary
Diet
Dietary Fats
Disease Models, Animal
Fatty Acids, Nonesterified
Female
Gallbladder Diseases
Gallbladder Emptying
Leptin
Lipids
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Obese
Obesity
Phospholipids
Triglycerides